Hemochromatosis and Autoimmune Conditions
- Thread starter RedFox
- Start date
My blood tests are back and, as I suspected, my ferritin is quite high - 367 - considering what the cutting edge experts consider to be healthiest.
I ordered some calcium EDTA and a book on chelation:
http://www.amazon.com/gp/product/1890572209/ref=oh_details_o01_s00_i00?ie=UTF8&psc=1
So I'm going to be making some liposomal EDTA to help with the "unloading".
I ordered some calcium EDTA and a book on chelation:
http://www.amazon.com/gp/product/1890572209/ref=oh_details_o01_s00_i00?ie=UTF8&psc=1
So I'm going to be making some liposomal EDTA to help with the "unloading".
revised February 4, 1999
Effects of Iron Overload
Hereditary Hemochromatosis
Total body iron overload occurs most often due either to hereditary hemochromatosis or to repeated transfusions in patients with severe anemia. Hereditary hemochromatosis is the more common of the two by far.
Hereditary haemochromatosis reflects a fractional increase in dietary iron absorption (Cox and Peters, 1978) (Cox and Peters, 1980) (Lynch et al., 1989). Tissue iron reaches dangerous levels after thirty or forty years. The gene responsible for hereditary haemochromatosis, HFE, resides on chromosome 6. Discovered in 1996, the gene encodes a protein that is homologous to the Class I HLA antigens (Feder, et al., 1996). The alteration in HFE protein that produces hereditary haemachromatosis involves the mutation of a cysteine to a leucine at position 282 (C282Y). People who have one copy of the mutant HFE gene are carriers who only rarely develop iron overload (usually in association with a second defect.) People with two copies of the mutant protein can develop iron overload and the myriad of problems that it can produce (see below). Nearly 90% of people who have hereditary haemochromatosis have the C282Y mutation in HFE (Nielson, et al., 1998).
Only recently have investigators gained insight into the mechanism by which the mutation in HFE alters cellular iron metabolism. Iron in the circulation is bound to the protein, transferrin, which maintains it in a non-toxic state. Cells contain receptors for transferrin on their plasma membranes which mediate cellular iron uptake. Transferrin receptors bind iron-transferrin complexes which are taken into endosomes. Iron is separated from transferrin in the endosome, and is shuttled into the interior of the cell. The iron-free transferrin (apotransferrin) is recycled into the circulation and is free to bind and transport additional iron atoms. The HFE protein associates with the transferrin receptor and prevents internalization of iron-transferrin complex into cells (Gross, et al., 1998). The HFE protein, in effect, acts as a brake on cellular iron uptake.
The C282Y mutation in HFE disrupts the folding of the protein (Lebron, et al., 1998). The mutant protein does not associate with the transferrin receptor and does not dampen iron uptake by cells. These insights do not fully explain the increase in gastrointestinal iron absorption, which is the root of hereditary hemochromatosis. They are, however, the first observations that mechanistically connect HFE and iron metabolism. Improved understanding of the complex process of intestinal iron absorption should surmount this shortcoming.
Hereditary hemachromatosis is remarkably common. About 10% to 12% of people of European background are heterozygous for the condition (Douabin, et al., 1999). The number of people who are homozygous for the condition approaches one in three hundred. This makes hereditary hemochromatosis one of the most prevalent genetic conditions in the world. Interestingly, the clinical expression of the disorder is less than frequency calculations predict. Variable penetrance, prerhaps related to secondary genetic or environemental conditions must influence clinical manifestations.
Transfusional Iron Overload
Transfusional iron overload occurs with severe, chronic anemias where patients survive for many years thanks to the transfusions. Conditions that fulfill this criteria include thalassemia major, myelodysplasia (including sideroblastic anemia), moderate aplastic anemia, and Diamond-Blackfan anemia. Iron accumulation with repeated transfusion reflects the retention of the heme iron from the transfused red cells after they become senscent and are destroyed. No physiological means of iron excretion exists. As a result, the element accumulates in all the body's organs, and particularly in the liver.
With transfusional iron overload, the senescent red cells are destroyed by reticuloendothelial cells. The iron is deposited onto transferrin, the protein responsible for iron transport in the blood. From here, the iron is distributed to all body tissues. With transfusional iron overload, excess iron occurs both in the reticuloendothelial cells and parenchymal cells. In contrast, with hereditary hemochromatosis the iron is placed directly onto transferrin and from there moves to the tissues. The distinguishing feature between transfusional iron overload and hereditary hemochromatosis is the presence of large deposits of iron in the reticuloendothelial cells with the former. The pattern of organ injury is the same with the two.
Consequences of Iron Overload
The effect of iron overload on some organs, such as the skin, are trivial, while hemosiderotic harm to others, such as the liver, can be fatal (Bassett et al., 1986). Few notable symptoms precede advanced injury. Abdominal discomfort, lethargy, and fatigue are common but nonspecific complaints. Dyspnea with exertion and peripheral edema indicate significant cardiac compromise and reflect advanced iron loading.
Liver
As the major site of iron storage, the liver is a conspicuous victim of excess iron depositon (Bonkovsky, 1991). Mild to moderate hepatomegaly develops early, followed by shrinkage produced by fibrosis and cirrhosis (Conte et al., 1986) (Bassett et al., 1986). Hepatic tenderness occurs occasionally.
Hematoxylin and eosin staining reveals a brownish pigment in the hepatocytes which Perl's Prussian blue staining unmasks as iron (Hultcrantz and Glaumann, 1982). Large amounts of iron are also deposited in Kupfer cells of patients with transfusional iron overload. Electron microscopy reveals substantial hemosiderin aggregates in addition to large quantities of ferritin.
As with many other conditions that injure the liver, hepatic damage secondary to excessive iron deposition produces fibrosis. With long standing hemochromatosis, micronodular cirrhosis can also develop. Hemosiderotic liver damage produces very little inflammation. Consequently, significant hepatic iron deposition and even fibrosis can occur with very little increase in the serum transaminase levels. Disturbances in liver synthetic function indicate advanced disease.
Heart
Congestive cardiomyopathy is the most common defect that occurs with iron overload, but other problems have been described including pericarditis, restrictive cardiomyopathy, and angina without coronary artery disease (Schellhammer et al., 1967) (Fitchett et al., 1980) (Sanyal et al., 1975) (Liu and Olivieri, 1994). A strong correlation exists between the cumulative number of blood transfusions and functional cardiac derangements in children with thalassemia (Wolfe et al., 1985) (Koren et al., 1987).
The physical examination is surprisingly benign even in patients with heavy cardiac iron deposition. Once evidence of cardiac failure appears, however, heart function rapidly deteriorates, often without response to medical intervention. Biventricular failure produces pulmonary congestion, peripheral edema, and hepatic engorgement. Vigorous iron extrication has reversed this potentially lethal complication on occasion (Rahko et al., 1986).
Iron deposition in the Bundle of His and the Purkinje system produces conduction defects (Buja and Roberts, 1971) (Olson et al., 1987). Sudden death is common in these patients, presumably due to arythmias. At one time, patients treated with the chelator desferrioxamine for transfusional iron overload received supplements of ascorbic acid in the range of 15 to 30 mg/kg per day to promote iron mobilization (O'Brien, 1977). Reports of sudden death prompted cessation of this practice (Nienhuis, 1981). At lower doses (2 to 4 mg/kg), ascorbic acid is a safe adjunct to chelation therapy in patients with transfusional iron overload.
Cardiac dysfunction can occur with very little tissue iron deposition. The total quantity of iron is less important than the unbound, or "toxic" iron subset. The concentration of unbound iron in tissues is extremely small, and virtually impossible to measure. This "toxic" iron is precisely the component bound and neutralized by iron chelators (in the case of desferrioxamine, the association constant is about 1032, see below). Therefore, cardiac damage is best prevented in patients with transfusional iron overload by maintaining a constant low level of chelator in the circulation (and consequently in the tissues, where the protection is rendered.) Chick cardiac myocytes in culture contract spontaneously. Iron salts added to the culture medium poison the cells and abrogate this function. Desferrioxamine chelates extracellular, and importantly intracellular iron, and restores myocyte contractility (Link G, et al. 1985).
Echocardiography in children and radionuclide ventriculography in adults are the most useful non-invasive diagnostic techniques. The echocardiographic abnormalities correlate roughly with the number of transfusions. Exercise radionuclide ventriculograms are particularly sensitive in the detection of cardiac dysfunction in patients with iron overload (Leon et al., 1979).
Endocrine
Dysfunction of the endocrine pancreas is common in patients with iron overload (Flynn et al., 1976). Some people develop overt diabetes mellitus requiring insulin therapy. The disturbances in carbohydrate metabolism are often more subtle, however. An oral glucose tolerance test often unmasks abnormal insulin production. Vigorous exorcism of the excess iron occasionally reverses the islet cell dysfunction (Bomford and Williams, 1976). Exocrine pancreatic function, in contrast, is usually well-preserved.
Pituitary dysfunction produces a plethora of endocrine disturbances (Costin et al., 1979). Reduced gonadotropin levels are common. When coupled with primary reductions in gonadal synthesis of sex steroids, this phenomenon delays sexual maturation in some children with transfusional iron overload. Secondary infertility is common (Schafer et al., 1981). Although Addison's syndrome is uncommon with iron overload, production of ACTH is occasionally deficient. A metapyrone stimulation test shows delayed or diminished pituitary secretion of ACTH (Schafer et al., 1985).
Thyroid function is usually well-preserved in patients with iron overload. In contrast, parathyroid activity is frequently compromised. Functional hypoparathyroidism can be demonstrated in many patients by inducting hypocalcemia with an intravenous bolus of ethelyenediamine tetraacetic acid (EDTA) while monitoring the production of parathyroid hormone (Gertner et al., 1979).
Miscellaneous Abnormalities with Iron Overload
Hyperpigmentation is a nonspecific skin response to a variety of insults including excessive exposure to ultraviolet light (tanning), thermal injury, and drug eruptions. Cutaneous iron deposition damages the skin and enhances melanin production by melanocytes. Ultraviolet light exposure and iron are often synergistic in the induction of skin pigmentation, so that many patients tan very readily. Fair-skinned people who routinely tan poorly often never develop hyperpigmentation despite very large body iron burdens, highlighting the genetic contribution to skin pigmentation. In contrast, patients with moderate baseline pigmentation (for example, people of Mediterranean descent) frequently develop a striking almond-colored hue. With particularly heavy iron overload, visible iron deposits sometimes appear in the skin as a grayish discoloration.
Arthropathy, a common feature with hereditary hemochromatosis, is rare in patients with secondary iron overload (Mathews and Williams, 1987). The large joints, such as the hips are affected most commonly (Axford et al., 1991). Decades of iron deposition in articular cartilage in hereditary hemochromatosis is the presumed cause of this condition. Chondrocalcinosis is a late but characteristic feature of the arthropathy seen in hereditary hemochromatosis. Other troubling musculoskeletal problems include severe, recurrent cramps and disabling myalgias. Muscle biopsy shows iron deposits in the myocytes, but the pathophysiologic connection to the pain and cramps is unclear.
Bone disease, manifested as osteoporosis, is a significant problem in patients with thalassemia. Bone marrow expansion often thins the bone cortex, making these patients very susceptible to fractures. The etiology of the bony disorder in patients with thalassemia is unclear. One possible contributor is the desferrioxamine used to prevent iron overload. The chelator has a very high specificity for iron. It may, however, chelate a small amount of the calcium that is necessary for the production of new bone. Over the years, a very low rate of mineral scavenging from bone by desferrioxime could contribute to osetoporosis.
Pulmonary hypertension is a problem that has been widely recognized only recently in patients with iron overload. A number of reports have involved patients with thalassemia major or thalassemia intermedia with iron overload (Aessopos, et al., 1995) (Grisaru D,et al., 1990) (Koren, et al., 1987). No report exists of similar problems in people with iron overload from other causes, such as hereditary hemochromatosis. The combination of iron overload in the pulmonary tissues and high blood flow through the pulmonary vascular bed may be at fault. More work is needed to clarify these issues.
Iron overload and Opportunistic Infections
Withholding iron from potential pathogens is one strategy used in host defense (Weinberg, 1978). Transferrin's extremely high affinity for iron, coupled with the fact that two-thirds of the iron binding sites of the protein normally are unoccupied, essentially eliminates free iron from plasma and extracellular tissues. Both transferrin and the structurally related protein, lactoferrin, are bacteriostatic in vitro for many bacteria (Bullen et al., 1971) (Reiter et al., 1975) (Lawrence 3d et al., 1977).
The very high transferrin saturations attained in patients with iron overload compromise the bacteriostatic properties of the protein. Iron sequestration is not a frontline defense against microbes. Therefore, iron overload does not produce the susceptibility to infection seen with defects in more central systems (e.g., chronic granulomatous disease.) Nonetheless, a number of infections, often with unusual organisms, have been reported in patients with iron overload (Abbott et al., 1986) (Brennan et al., 1983) (Bullen et al., 1991) (Capron et al., 1984):
Table 1. Infections in Patients with Iron Overload Listeria monocytogenes
Yersinia enterocolitica
Yersinia pesudotuberculosis
Rhizopus orayzae
Salmonella typhimurium
Cunninghamella berthollethiae
Pasturella pseudotuberculosis
Vibrio vulnifus
Clostridium perfringens
Sideroblastic anemia often produces neutropenia or neutrophil dysfunction. Host defense is compromised even further in patients with sideroblastic anemia who develop secondary iron overload. Although aggressive antimicrobial therapy is often successful, some infections, such as the mucormycosis produced by Rhizopus oryazae, are almost uniformally fatal.
The iron chelator, desferrioxamine, has also been implicated in opportunistic infection with unusual organisms such as Rhizopus orayzae, the cause of mucormycosis, in some patients with iron overload (Boelaert et al., 1988) (Rex et al., 1988) (Daly et al., 1989). Streptomyces pilosis synthesizes this siderophore when grown in an iron-deficient environment. Desferrioxamine is released in the vicinity of these microbes, binds iron, and returns the element to the microorganisms to support growth and replication. Some pathogenic bacteria and fungi can utilize desferrioxamine-bound iron to promote their growth, thereby enhancing the risk of severe infection (Robins-Browne and Prpic, 1985).
The question of when to begin chelation therapy in a patient with transfusional hemochromatosis lacks a simple answer (Fargion et al., 1982). The decision must be carefully individualized. Serious infection in patients treated with desferrioxamine is uncommon, and the benefits of therapy to prevent iron-induced organ damage generally outweigh the risk of infectious complications.
References:
Abbott, M., Galloway, A., and Cunningham, J. (1986). Haemochromatosis presenting with a double Yersinia infection. Journal of Infection 13, 143-145.
Aessopos A, Stamatelos G, Skoumas V, Vassilopoulos G, Mantzourani M, Loukopoulos, D. (1995). Pulmonary hypertension and right heart failure in patients with ß- thalassemia intermedia. Chest 107, 50-53.
Axford, J., Bomford, A., Revell, P., Watt, I., Williams, R., and Hamilton, E. (1991). Hip arthropathy in genetic hemochromatosis. Radiographic and histologic features. Arthritis Rheum 34, 357-61.
Bassett, M., Halliday, J., and Powell, L. (1981). HLA typing in idiopathic hemochromatosis: distinction between homozygotes and heterozygotes with biochemical expression. Hepatology 1, 120-126.
Bassett, M., Halliday, J., and Powell, L. (1986). Value of hepatic iron measurements in early hemochromatosis and determination of the critical iron level associated with fibrosis. Hepatology 6, 24-28.
Boelaert, J., van Roost, G., Vergauwe, P., Verbanck, J., de Vroey, C., and Segaert, M. (1988). The role of desferrioxamine in dialysis-associated mucormycosis: report of three cases and review of the literature. Clinical Nephrology 29, 261-266.
Bomford, A., and Williams, R. (1976). Long term results of venesection therapy in idiopathic haemochromatosis. Quarterly Journal of Medicine 45, 611-23.
Bonkovsky, H. (1991). Iron and the liver. American Journal of Medical Science 301, 32-43.
Brennan, R., Crain, B., Proctor, A., and Burack, D. (1983). Cunninghamella: a newly recognized cause of rhinocerebral mucormycosis. American Journal of Clinical Pathology 80, 98-102.
Buja, L., and Roberts, W. (1971). Iron in the heart. American Journal of Medicine 51, 209-221.
Bullen, J. J., Spaulding, P. B., Ward, C. G., and Gutteridge, J. M. C. (1991). Hemochromatosis, iron and septicemia caused by Vibrio vulnificus. Archives of Internal Medicine 151, 1606-1609.
Capron, J., Capron-Chivrac, D., Tossou, H., Delamarre, J., and Eb, F. (1984). Spontaneous Yersinia enterocolitica peritonitis in idiopathic hemochromatosis. Gastroenterology 87, 1372-1375.
Conte, D., Piperno, A., Mandelli, C., Fargion, S., Cesana, M., Brunelli, L., Ferrario, L., Velio, P., Zaramella, M., Tiribelli, C., and al, e. (1986). Clinical, biochemical and histological features of primary haemochromatosis: a report of 67 cases. Liver 6, 310-5.
Costin, G., Kogut, M., Hyman, C., and Ortega, J. (1979). Endocrine abnormalities in thalassemia major. American Journal of Disease of Childhood 133, 497-502.
Cox, T., and Peters, T. (1978). Uptake of iron by duodenal biopsy specimens from patients with iron-deficiency anaemia and primary haemochromatosis. Lancet 1, 123-4.
Cox, T., and Peters, T. (1980). In vitro studies of duodenal iron uptake in patients with primary and secondary iron storage disease. Q J Med 49, 249-57.
Daly, A., Velazquez, L., Bradley, S., and Kauffman, C. (1989). Mucormycosis: association with deferoxamine therapy. American Journal of Medicine 87, 468-471.
Douabin V, Moirand, R, Jouanolle A, Brissot P, Le Gall J, Deugnier Y, David V. 1999. Polymorphisms in the HFE Gene. Hum Here 49: 21-26.
Edwards, C., Dadone, M., Skolnick, M., and Kushner, J. (1982). Hereditary haemachromatosis. Clinical Haematology 11, 411-435.
Fargion, S., Taddei, M., Gabutti, V., Piga, A., DiPalma, A., Capra, L., Fontanelli, G., and Avanzini, A. (1982). Early iron overload in beta-thalassaemia major: when to start chelation therapy? Archives of Diseases of Childhood 57, 929.
Feder, J., Gnirke, A., Thomas, W., Tsuchihashi, Z., and al., e. (1996). A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nature Genetics 13, 399-408.
Fitchett, D., Coltart, D., Littler, W., MJ, L., Trueman, T., Gozzard, D., and Peters, T. (1980). Cardiac involvement in secondary hemochromatosis. Cardiovascular Research 14, 7199-7284.
Flynn, D., Fairney, A., Jackson, D., and Clayton, B. (1976). Hormonal changes in thalassemia major. Archives of Diseases of Childhood 51, 828-836.
Gertner, J., Broadus, A., Anast, C., Grey, M., Pearson, H., and Genel, M. (1979). Impaired parathroid response to induced hypocalcemia in thalassemia major. Journal of Pediatrics 95, 210-213.
Grisaru D, Rachmilewitz EA, Mosseri M, Gotsman M, Lafair JS, Okon E, Goldfarb A, Hasin Y. (1990) Cardiopulmonary assessment in beta-thalassemia major. Chest 98, 1138-1142.
Gross CN, Irrinki A, Feder JN, Enns CA. 1998. Co-trafficking of HFE, a nonclassical major histocompatibility complex class I protein, with the transferrin receptor implies a role in intracellular iron regulation. J. Biol. Chem. 273: 22068-22074.
Hultcrantz, R., and Glaumann, H. (1982). Studies on the rat liver following iron overload. Biochemical analysis following iron mobilization. Laboratory Investigation 46, 383-393.
Koren, A., Garty, I., Antonelli, D., and Katzuni, E. (1987). Right ventricular cardiac dysfunction in beta-thalassemia major. American Journal of Diseases of Childhood 141, 93-96.
Lawrence 3d, T., Biggers, C., and Simonton, P. (1977). Bacteriostatic inhibition of Klebsiella pneumoniae by three human transferrins. Ann Hum Biol 4, 281-4.
Lebron JA, Bennett MJ, Vaughn, DE, Chirino AJ, Snow PM, Mintier GA, Feder JN, Bjorkman PJ. 1998. Crystal structure of the hemochromatosis protein HFE and characterization of its interaction with transferrin receptor. Cell 93: 111-123.
Leon, M., Borer, J., Bacharach, S., Green, M., Benz, E., Griffith, P., and Nienhuis, A. (1979). Detection of early cardiac dysfunction in patients with severe beta-thalassemia and chronic iron overload. New England Journal of Medicine 301, 1143-1148.
Link G, Pinson A, Hershko C . 1985. Heart cells in culture: a model of myocardial iron overload and chelation. J. Lab. Clin. Med. 106: 147-153.
Liu, P., and Olivieri, N. (1994). Iron overload cardiomyopathies: new insights into an old disease. Cardiovasc Drugs Ther 8, 101-10.
Lynch, S., Skikne, B., and Cook, J. (1989). Food iron absorption in idiopathic hemochromatosis. Blood 74, 2187-93.
Mathews, J., and Williams, H. (1987). Arthritis in hereditary hemochromatosis. Arthritis Rheum 30, 1137-41.
Nielsen P, Carpinteiro S, Fischer R, Cabeda JM, Porto G, Gabbe EE. 1998. Prevalence of the C282Y and H63D mutations in the HFE gene in patients with hereditary haemochromatosis and in control subjects from Northern Germany. Brit. J Haematol. 103:842-845.
Nienhuis, A. (1981). Vitamin C and Iron. New England Journal of Medicine 304, 170-171.
O'Brien, R. (1977). Iron overload: clinical and pathologic aspects in pediatrics. Seminars in Haematology 14, 115-125.
Olson, L., Edwards, W., McCall, J., Ilstup, D., and Gersh, B. (1987). Cardiac iron deposition in idiopathic hemochromatosis: Histologic and analytic assessment of 14 hearts from autopsy. Journal of the American College of Cardiology 10, 1239-1243.
Rahko, P., Salerni, R., and Uretsky, B. (1986). Successful reversal by chelation therapy of congestive cardiomyopathy due to iron overload. Journal of the American College of Cardiology 8, 436-440.
Reiter, B., Brock, J., and Steel, E. (1975). Inhibition of Escherichia coli by bovine colostrum and post-colostral milk. II. The bacteriostatic effect of lactoferrin on a serum susceptible and serum resistant strain of E. coli. Immunology 28, 83-95.
Rex, J., Ginsberg, A., Fries, L., Pass, H., and Kwon-Chung, K.-J. (1988). Cunninghamella bertholletiae infection associated with deferoxamine therapy. Reviews of Infectious Diseases 10, 1187-1194.
Robins-Browne, R., and Prpic, J. (1985). Effects of iron and desferrioxamine on infections with Yersinia enterocolitica. Infection and Immunity 47, 774-779.
Sanyal, S., Johnson, W., Jayalakshamma, B., and Green, A. (1975). Fatal "iron heart" in an adolescent: biochemical and ultrastructural aspects of the heart. Pediatrics 55, 336-341.
Schafer, A., Cheron, R., Dluhy, R., Cooper, B., Gleason, R., Soeldner, J., and Bunn, H. (1981). Clinical consequences of acquired transfusional iron overload in adults. New England Journal of Medicine 304, 319-324.
Schafer, A., Rabinowe, S., Le Boff, M., Bridges, K., Cheron, R., and Dluhy, R. (1985). Long-term efficacy of deferoxamine iron chelation therapy in adults with acquired transfusional iron overload. Archives of Internal Medicine 45, 1217-1221.
Schellhammer, P., Engle, M., and Hagstrom, J. (1967). Histochemical studies of the myocardium and conduction system in acquired iron-storage disease. Circulation 35, 631-637.
Weinberg, E. (1978). Iron and infection. Microbial Reviews 42, 46-66.
Wolfe, L., Olivieri, N., Sallan, D., Colan, S., Rose, V., Propper, R., Freedman, M., and Nathan, D. (1985). Prevention of cardiac disease by subcutaneous deferoxamine in patients with thalassemia major. New England Journal of Medicine 312, 1600-1603.
Effects of Iron Overload
Hereditary Hemochromatosis
Total body iron overload occurs most often due either to hereditary hemochromatosis or to repeated transfusions in patients with severe anemia. Hereditary hemochromatosis is the more common of the two by far.
Hereditary haemochromatosis reflects a fractional increase in dietary iron absorption (Cox and Peters, 1978) (Cox and Peters, 1980) (Lynch et al., 1989). Tissue iron reaches dangerous levels after thirty or forty years. The gene responsible for hereditary haemochromatosis, HFE, resides on chromosome 6. Discovered in 1996, the gene encodes a protein that is homologous to the Class I HLA antigens (Feder, et al., 1996). The alteration in HFE protein that produces hereditary haemachromatosis involves the mutation of a cysteine to a leucine at position 282 (C282Y). People who have one copy of the mutant HFE gene are carriers who only rarely develop iron overload (usually in association with a second defect.) People with two copies of the mutant protein can develop iron overload and the myriad of problems that it can produce (see below). Nearly 90% of people who have hereditary haemochromatosis have the C282Y mutation in HFE (Nielson, et al., 1998).
Only recently have investigators gained insight into the mechanism by which the mutation in HFE alters cellular iron metabolism. Iron in the circulation is bound to the protein, transferrin, which maintains it in a non-toxic state. Cells contain receptors for transferrin on their plasma membranes which mediate cellular iron uptake. Transferrin receptors bind iron-transferrin complexes which are taken into endosomes. Iron is separated from transferrin in the endosome, and is shuttled into the interior of the cell. The iron-free transferrin (apotransferrin) is recycled into the circulation and is free to bind and transport additional iron atoms. The HFE protein associates with the transferrin receptor and prevents internalization of iron-transferrin complex into cells (Gross, et al., 1998). The HFE protein, in effect, acts as a brake on cellular iron uptake.
The C282Y mutation in HFE disrupts the folding of the protein (Lebron, et al., 1998). The mutant protein does not associate with the transferrin receptor and does not dampen iron uptake by cells. These insights do not fully explain the increase in gastrointestinal iron absorption, which is the root of hereditary hemochromatosis. They are, however, the first observations that mechanistically connect HFE and iron metabolism. Improved understanding of the complex process of intestinal iron absorption should surmount this shortcoming.
Hereditary hemachromatosis is remarkably common. About 10% to 12% of people of European background are heterozygous for the condition (Douabin, et al., 1999). The number of people who are homozygous for the condition approaches one in three hundred. This makes hereditary hemochromatosis one of the most prevalent genetic conditions in the world. Interestingly, the clinical expression of the disorder is less than frequency calculations predict. Variable penetrance, prerhaps related to secondary genetic or environemental conditions must influence clinical manifestations.
Transfusional Iron Overload
Transfusional iron overload occurs with severe, chronic anemias where patients survive for many years thanks to the transfusions. Conditions that fulfill this criteria include thalassemia major, myelodysplasia (including sideroblastic anemia), moderate aplastic anemia, and Diamond-Blackfan anemia. Iron accumulation with repeated transfusion reflects the retention of the heme iron from the transfused red cells after they become senscent and are destroyed. No physiological means of iron excretion exists. As a result, the element accumulates in all the body's organs, and particularly in the liver.
With transfusional iron overload, the senescent red cells are destroyed by reticuloendothelial cells. The iron is deposited onto transferrin, the protein responsible for iron transport in the blood. From here, the iron is distributed to all body tissues. With transfusional iron overload, excess iron occurs both in the reticuloendothelial cells and parenchymal cells. In contrast, with hereditary hemochromatosis the iron is placed directly onto transferrin and from there moves to the tissues. The distinguishing feature between transfusional iron overload and hereditary hemochromatosis is the presence of large deposits of iron in the reticuloendothelial cells with the former. The pattern of organ injury is the same with the two.
Consequences of Iron Overload
The effect of iron overload on some organs, such as the skin, are trivial, while hemosiderotic harm to others, such as the liver, can be fatal (Bassett et al., 1986). Few notable symptoms precede advanced injury. Abdominal discomfort, lethargy, and fatigue are common but nonspecific complaints. Dyspnea with exertion and peripheral edema indicate significant cardiac compromise and reflect advanced iron loading.
Liver
As the major site of iron storage, the liver is a conspicuous victim of excess iron depositon (Bonkovsky, 1991). Mild to moderate hepatomegaly develops early, followed by shrinkage produced by fibrosis and cirrhosis (Conte et al., 1986) (Bassett et al., 1986). Hepatic tenderness occurs occasionally.
Hematoxylin and eosin staining reveals a brownish pigment in the hepatocytes which Perl's Prussian blue staining unmasks as iron (Hultcrantz and Glaumann, 1982). Large amounts of iron are also deposited in Kupfer cells of patients with transfusional iron overload. Electron microscopy reveals substantial hemosiderin aggregates in addition to large quantities of ferritin.
As with many other conditions that injure the liver, hepatic damage secondary to excessive iron deposition produces fibrosis. With long standing hemochromatosis, micronodular cirrhosis can also develop. Hemosiderotic liver damage produces very little inflammation. Consequently, significant hepatic iron deposition and even fibrosis can occur with very little increase in the serum transaminase levels. Disturbances in liver synthetic function indicate advanced disease.
Heart
Congestive cardiomyopathy is the most common defect that occurs with iron overload, but other problems have been described including pericarditis, restrictive cardiomyopathy, and angina without coronary artery disease (Schellhammer et al., 1967) (Fitchett et al., 1980) (Sanyal et al., 1975) (Liu and Olivieri, 1994). A strong correlation exists between the cumulative number of blood transfusions and functional cardiac derangements in children with thalassemia (Wolfe et al., 1985) (Koren et al., 1987).
The physical examination is surprisingly benign even in patients with heavy cardiac iron deposition. Once evidence of cardiac failure appears, however, heart function rapidly deteriorates, often without response to medical intervention. Biventricular failure produces pulmonary congestion, peripheral edema, and hepatic engorgement. Vigorous iron extrication has reversed this potentially lethal complication on occasion (Rahko et al., 1986).
Iron deposition in the Bundle of His and the Purkinje system produces conduction defects (Buja and Roberts, 1971) (Olson et al., 1987). Sudden death is common in these patients, presumably due to arythmias. At one time, patients treated with the chelator desferrioxamine for transfusional iron overload received supplements of ascorbic acid in the range of 15 to 30 mg/kg per day to promote iron mobilization (O'Brien, 1977). Reports of sudden death prompted cessation of this practice (Nienhuis, 1981). At lower doses (2 to 4 mg/kg), ascorbic acid is a safe adjunct to chelation therapy in patients with transfusional iron overload.
Cardiac dysfunction can occur with very little tissue iron deposition. The total quantity of iron is less important than the unbound, or "toxic" iron subset. The concentration of unbound iron in tissues is extremely small, and virtually impossible to measure. This "toxic" iron is precisely the component bound and neutralized by iron chelators (in the case of desferrioxamine, the association constant is about 1032, see below). Therefore, cardiac damage is best prevented in patients with transfusional iron overload by maintaining a constant low level of chelator in the circulation (and consequently in the tissues, where the protection is rendered.) Chick cardiac myocytes in culture contract spontaneously. Iron salts added to the culture medium poison the cells and abrogate this function. Desferrioxamine chelates extracellular, and importantly intracellular iron, and restores myocyte contractility (Link G, et al. 1985).
Echocardiography in children and radionuclide ventriculography in adults are the most useful non-invasive diagnostic techniques. The echocardiographic abnormalities correlate roughly with the number of transfusions. Exercise radionuclide ventriculograms are particularly sensitive in the detection of cardiac dysfunction in patients with iron overload (Leon et al., 1979).
Endocrine
Dysfunction of the endocrine pancreas is common in patients with iron overload (Flynn et al., 1976). Some people develop overt diabetes mellitus requiring insulin therapy. The disturbances in carbohydrate metabolism are often more subtle, however. An oral glucose tolerance test often unmasks abnormal insulin production. Vigorous exorcism of the excess iron occasionally reverses the islet cell dysfunction (Bomford and Williams, 1976). Exocrine pancreatic function, in contrast, is usually well-preserved.
Pituitary dysfunction produces a plethora of endocrine disturbances (Costin et al., 1979). Reduced gonadotropin levels are common. When coupled with primary reductions in gonadal synthesis of sex steroids, this phenomenon delays sexual maturation in some children with transfusional iron overload. Secondary infertility is common (Schafer et al., 1981). Although Addison's syndrome is uncommon with iron overload, production of ACTH is occasionally deficient. A metapyrone stimulation test shows delayed or diminished pituitary secretion of ACTH (Schafer et al., 1985).
Thyroid function is usually well-preserved in patients with iron overload. In contrast, parathyroid activity is frequently compromised. Functional hypoparathyroidism can be demonstrated in many patients by inducting hypocalcemia with an intravenous bolus of ethelyenediamine tetraacetic acid (EDTA) while monitoring the production of parathyroid hormone (Gertner et al., 1979).
Miscellaneous Abnormalities with Iron Overload
Hyperpigmentation is a nonspecific skin response to a variety of insults including excessive exposure to ultraviolet light (tanning), thermal injury, and drug eruptions. Cutaneous iron deposition damages the skin and enhances melanin production by melanocytes. Ultraviolet light exposure and iron are often synergistic in the induction of skin pigmentation, so that many patients tan very readily. Fair-skinned people who routinely tan poorly often never develop hyperpigmentation despite very large body iron burdens, highlighting the genetic contribution to skin pigmentation. In contrast, patients with moderate baseline pigmentation (for example, people of Mediterranean descent) frequently develop a striking almond-colored hue. With particularly heavy iron overload, visible iron deposits sometimes appear in the skin as a grayish discoloration.
Arthropathy, a common feature with hereditary hemochromatosis, is rare in patients with secondary iron overload (Mathews and Williams, 1987). The large joints, such as the hips are affected most commonly (Axford et al., 1991). Decades of iron deposition in articular cartilage in hereditary hemochromatosis is the presumed cause of this condition. Chondrocalcinosis is a late but characteristic feature of the arthropathy seen in hereditary hemochromatosis. Other troubling musculoskeletal problems include severe, recurrent cramps and disabling myalgias. Muscle biopsy shows iron deposits in the myocytes, but the pathophysiologic connection to the pain and cramps is unclear.
Bone disease, manifested as osteoporosis, is a significant problem in patients with thalassemia. Bone marrow expansion often thins the bone cortex, making these patients very susceptible to fractures. The etiology of the bony disorder in patients with thalassemia is unclear. One possible contributor is the desferrioxamine used to prevent iron overload. The chelator has a very high specificity for iron. It may, however, chelate a small amount of the calcium that is necessary for the production of new bone. Over the years, a very low rate of mineral scavenging from bone by desferrioxime could contribute to osetoporosis.
Pulmonary hypertension is a problem that has been widely recognized only recently in patients with iron overload. A number of reports have involved patients with thalassemia major or thalassemia intermedia with iron overload (Aessopos, et al., 1995) (Grisaru D,et al., 1990) (Koren, et al., 1987). No report exists of similar problems in people with iron overload from other causes, such as hereditary hemochromatosis. The combination of iron overload in the pulmonary tissues and high blood flow through the pulmonary vascular bed may be at fault. More work is needed to clarify these issues.
Iron overload and Opportunistic Infections
Withholding iron from potential pathogens is one strategy used in host defense (Weinberg, 1978). Transferrin's extremely high affinity for iron, coupled with the fact that two-thirds of the iron binding sites of the protein normally are unoccupied, essentially eliminates free iron from plasma and extracellular tissues. Both transferrin and the structurally related protein, lactoferrin, are bacteriostatic in vitro for many bacteria (Bullen et al., 1971) (Reiter et al., 1975) (Lawrence 3d et al., 1977).
The very high transferrin saturations attained in patients with iron overload compromise the bacteriostatic properties of the protein. Iron sequestration is not a frontline defense against microbes. Therefore, iron overload does not produce the susceptibility to infection seen with defects in more central systems (e.g., chronic granulomatous disease.) Nonetheless, a number of infections, often with unusual organisms, have been reported in patients with iron overload (Abbott et al., 1986) (Brennan et al., 1983) (Bullen et al., 1991) (Capron et al., 1984):
Table 1. Infections in Patients with Iron Overload Listeria monocytogenes
Yersinia enterocolitica
Yersinia pesudotuberculosis
Rhizopus orayzae
Salmonella typhimurium
Cunninghamella berthollethiae
Pasturella pseudotuberculosis
Vibrio vulnifus
Clostridium perfringens
Sideroblastic anemia often produces neutropenia or neutrophil dysfunction. Host defense is compromised even further in patients with sideroblastic anemia who develop secondary iron overload. Although aggressive antimicrobial therapy is often successful, some infections, such as the mucormycosis produced by Rhizopus oryazae, are almost uniformally fatal.
The iron chelator, desferrioxamine, has also been implicated in opportunistic infection with unusual organisms such as Rhizopus orayzae, the cause of mucormycosis, in some patients with iron overload (Boelaert et al., 1988) (Rex et al., 1988) (Daly et al., 1989). Streptomyces pilosis synthesizes this siderophore when grown in an iron-deficient environment. Desferrioxamine is released in the vicinity of these microbes, binds iron, and returns the element to the microorganisms to support growth and replication. Some pathogenic bacteria and fungi can utilize desferrioxamine-bound iron to promote their growth, thereby enhancing the risk of severe infection (Robins-Browne and Prpic, 1985).
The question of when to begin chelation therapy in a patient with transfusional hemochromatosis lacks a simple answer (Fargion et al., 1982). The decision must be carefully individualized. Serious infection in patients treated with desferrioxamine is uncommon, and the benefits of therapy to prevent iron-induced organ damage generally outweigh the risk of infectious complications.
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FAQ's ABOUT HEMOCHROMATOSIS/IRON OVERLOAD
Please note: This information has been compiled with the advice of leading doctors/researchers as well as HH patients themselves. This information is based on the following premise that this is the information we would give to a family member, where "money was no object", and the latest information on health options was wished. Through this premise, the most thorough and aggressive health care can be suggested. Each patient should confer with his/her physician about their own health care. If a physician does not regularly treat HH patients, he/she should consult with a medical expert. AHS can provide such experts. Sandra Thomas, President, American Hemochromatosis Society
Q: What is iron overload, hemochromatosis?
A: Hemochromatosis (pronounced: He-mo-chro-ma-toe-sis) is a genetic condition of abnormal iron metabolism that permits absorption of too much iron from an ordinary diet. Hereditary hemochromatosis is an autosomal recessive disorder. It is NOT a blood disease. It is also known as iron overload or iron storage disease. It is possible for someone who has never had an iron pill in his/her life to have iron overload.
Q: Can iron overload be acquired?
A: Yes, iron overload can be acquired. The genetic form is known as primary hemochromatosis, hereditary hemochromatosis (HH) or (HHC), or genetic hemochromatosis (GH) and idiopathic hemochromatosis (from an unknown origin), a term which is rarely used anymore. The acquired form (through massive doses of iron pills or blood transfusions) is known as secondary hemochromatosis, acquired hemochromatosis, or transfusional iron overload.
Q: How common is iron overload/hemochromatosis?
A: Frequency (incidence in the general population) of the abnormal gene is: 1 in 100-200 people has hemochromatosis (double gene mutation known as a homozygote) and 1 in 8-10 people is a carrier of hemochromatosis (single gene mutation known as a heterozygote or "het" for short). That's approximately 32 million Americans who are carriers and 1.5 million Americans have the double gene which can lead to full blown hemochromatosis. Recent studies in Ireland, show a frequency of 1 in 4 as carriers of the single mutation and 1 in 64 as double gene mutation. Because of this high frequency, routine screening for hereditary hemochromatosis is medically indicated.
Q: Who is affected by iron overload/hemochromatosis?
A: Most affected people DO NOT KNOW they are accumulating dangerous stores of iron. Tragically underdiagnosed, no race, age, or gender is immune. (Premenopausal women do have iron overload as well as young children) The American Hemochromatosis Society (AHS) has made an official position statement and issued guidelines for diagnosis, treatment, and management of iron overload/hereditary hemochromatosis, including recommendations that all Americans age 2 years and older be routinely and universally screened for iron overload as well as genetic screening. All ethnic groups can be affected, but those with an Irish/Scottish/Celtic/British heritage have an even higher prevalence of the HH mutation. Hispanics and Afro Americans also have iron overload.
Q: How serious is iron overload, hemochromatosis?
A: The excess iron injures body organs and KILLS unless detected in time for adequate iron storage removal. It is a very serious disease, but quite benign if detected early before organ damage has occurred. That is why routine screening is so important. HH is a lethal but treatable disease. Don't let anyone tell you that iron overload/HH is "nothing to worry about". The higher the ferritin level, the potential for serious organ damage is increased. An early diagnosis offers the patient a normal life span.
Q: Is there anything that can be done to treat or prevent iron overload?
A: Yes. Hereditary hemochromatosis is one of the few genetic diseases which has a prevention plan so that all organ damage and premature death can be completely prevented. When the excess iron IS detected EARLY and is ADEQUATELY removed, the individual can enjoy a normal life span in normal health. The motto of the American Hemochromatosis Society is: "Prevention through Genetic Testing".
Q: What are the symptoms of iron overload, hemochromatosis?
A: Patients can have iron overload and NOT have symptoms (asymptomatic) and that is the best time to diagnose the patient. Many doctors have been taught to look for "signs and symptoms" of HH but by the time symptoms appear, it is often too late to save the patient's life. Iron overload and storage in vital body organs can damage and may cause:
chronic fatigue (the most common complaint by patients);
cirrhosis/cancer of the liver (with or without a history of alcohol use);
arthritis/joint pain;
impotence/sterility/infertility; early menopause/irregular menses;
hair loss; hair thinning
diabetes (bronze diabetes, a darkening, graying of the skin not caused by sun exposure);
cancer (cancer thrives on iron); (especially primary liver cancer)
abdominal pain/swelling;
weight loss;
frequent colds/flu/infections, compromised immune system;
headaches;
hypothyroidism; (low thyroid)
heart irregularities/heart failure/heart attack (especially in younger men);
cirrhosis of the liver (with or without a history of alcohol use);
hepatoma/liver cancer (the leading cause of death in HH);
premature death.
Anyone with any combination of these symptoms, or a family history of these symptoms, should be tested for HH immediately. But remember, two important facts:
1.) There can be numerous generations of "silent carriers" of the mutation who never become ill and live to old age thereby giving a "false security" that HH doesn't "run in the family"
2.) Some patients do not have symptoms until they are end stage and their lives cannot be saved. Early detection should be achieved through:
1.) Knowledge of genetic risk through DNA Testing
2.) Annual screening with serum iron, TIBC, and serum ferritin to assure that iron storage is not taking place.
Q: I went to the blood bank and they told me I was anemic; how could I have iron overload at the same time?
A: Blood banks do NOT screen for iron overload/hemochromatosis. They are basing their comments on the hematocrit or hemoglobin readings that they take prior to a blood donation (the finger prick test) and these are not the correct tests for iron overload storage! Yet blood banks continue to give out false information to their clients, telling them that they have low "iron" or even in some cases that their iron is high! The iron-overloaded person may be anemic at the same time. There are several types of anemia that are iron-loading! Hematocrit and hemoglobin are NOT tests for iron overload/hemochromatosis; ask your physician to test you with transferrin saturation (TS) which is calculated by dividing the serum iron by the TIBC (total iron binding capacity) and serum ferritin to confirm or rule out iron overload.
Q: How can I know if I have iron overload/hemochromatosis? What tests should be performed? I hear that there is a DNA genetic test kit for hemochromatosis, is that true?
A: A simple series of blood tests which can be performed by any doctor or lab can indicate iron levels. They must be proper iron measures: Total Iron Binding Capacity (TIBC) together with Serum Iron. Divide TIBC into Serum Iron to get the percentage of transferrin saturation. It is important that the serum ferritin is also performed at the same time and it should be done, if possible, while fasting. Refrain from iron pills for a week prior to the tests. A new test, serum ferritin-iron assay will also be available in the near future. The discovery of the hemochromatosis gene was announced in August 1996 by Mercator Genetics Inc. of Menlo Park, California (which was purchased by Progenitor in 1997. Bio-Rad Laboratories of Hercules, CA bought the patent from Progenitor. Bio-Rad currently holds the patent to the HFE mutation). The new genetic DNA test (HLA-H now known as HFE or HFe) has been commercially commercially available from many labs around the nation since 2/1997, including SmithKline Beecham Clinical Laboratories currently known as Quest Diagnostics on a nationwide basis. Many university labs and other smaller independent genetics labs across the nation now offer the DNA testing for HH. In the early years, many of them only tested for the one mutation (845A also known as Cys282tyr), but today most labs test for BOTH HH mutations (845A and 187G also known as cys282 and his63). There is a 3rd gene mutation, 65S, but it is not included in most labs' testing protocols. Several labs also test for both gene mutations and offer a handy "cheek brush" tissue collection kit which you can get through the mail and perform in the privacy of your own home: Kimball Genetics in Denver, Colorado (1-800-320-1807 or 303-320-1807 in Denver or outside of the U.S.A.) The "cheek brush" method (no needles/blood/pain) is great for kids and adults. More info on how to order these tests is available from the AHS office at 407-829-4488. If you wish to get genetic DNA testing without using a doctor or having the results on your medical records, you may contact HealthCheckUSA (www.healthcheckusa.com) or call on their toll free number: 1-800-929-2044, to order the Kimball Genetics Lab DNA test kit. The results are private and confidential and are mailed directly to the patient, thusly protecting the patient's medical information. You may contact the lab directly for current prices. Genetic counselors are available to patients as part of the cost of the testing. The American Hemochromatosis Society strongly urges patients and their family members (male and female) to be genetically tested, including children, teens, young adults and seniors. If you have a question about your genetic testing, feel free to contact the AHS office directly for more information.
Q: I had the blood tests for iron overload and my doctor says I am "fine"; do I need to worry about it now?
A: First of all, always get copies of your medical lab reports for your home medical file and review them yourself. Make sure that the serum iron, TIBC, and serum ferritin tests are on the report and double check to make sure that you fall into the "safe zone" set by AHS--a ferritin under 150 and a saturation percentage of under 40%. Some labs have very "high" normal levels and you might not really be in a safe zone. Many patients have contacted us who have iron studies in the "danger zone" but their doctors have told them that they are fine. It is prudent to find out for yourself. The same philosophy applies to the DNA test--make sure you get copies of the report for your own files and know if you have the single or double mutation and which of the two mutations you carry (you can even carry one of each mutation which would make you known as a compound heterozygote).
Q: I've had the iron profile tests, read them myself and they were within the normal range; do I need to be retested ever again and/or have the DNA genetic test, especially since I feel fine?
A: Yes. Even if your first test was negative, ideally, you should be monitored annually by your physician. Also, by having the DNA test, you can discover if you have the single or double gene for hemochromatosis and determine your risk factor of developing full blown hemochromatosis or passing a mutation to offspring. A very small percentage (about 12% to 15%) of patients who are clinically iron overloaded (have high TS and serum ferritin levels) may have a negative result on the genetic test. Scientists believe that these persons have still another HH mutation (which has yet to be discovered and a test for it developed) which is causing this iron storage. For this reason, it is always wise to test using the transferrin saturation and serum ferritin annually to be on the safe side.
Q: What iron levels are considered "suspicious" for iron overload/hemochromatosis?
A: A percent of saturation of more than 40% and/or a serum ferritin of more than 150 are considered suspicious for iron overload/hemochromatosis. It is important to note that in some patients, the percent of saturation can be quite high while the ferritin rather low (this is often the case in children or young adults in their 20's) or conversely, with normal percent of saturation and a high serum ferritin. Genetic testing can, in most cases, confirm the diagnosis so that treatment can begin. Ask your doctor about liver function tests, if these are also elevated, that is another possible sign of HH.
Q: How is a diagnosis for iron overload/hemochromatosis confirmed?
A: Confirmation of a diagnosis is based on a combination of several factors; these will vary from doctor to doctor on which ones are used:
a.) Elevation of iron tests such as transferrin saturation and serum ferritin
b.) Elevation of liver enzymes (abnormal liver function tests)
c.) Symptoms (diabetes/heart disease/arthritis/impotence/infertility/bronzed skin, liver disease)
d.) Liver biopsy showing hepatic iron index (HII) and such liver diseases as cirrhosis/cancer
e.) DNA genetic test (results are available between 1 to 14 days depending on the lab used)
f.) CT/MRI/Ultrasound of the liver showing deposition of iron in the liver or hepatoma(s) (liver tumors).
g.) Quantitative phlebotomy (a trial series of six weekly phelobotomies to confirm diagnosis; if the hematocrit remains 35% or greater immediately prior to each phlebotomy. Six weeks of weekly bloodletting is another way to confirm iron overload, hemochromatosis)
h.) Alpha Fetoprotein bloodwork ruling out liver cancer due to HH.
i.) EKG to rule out heart damage from HH.
j.) Family history of iron overload, especially parents/siblings, who should also be screened with transferrin saturation and serum iron and genetic tests for comparison. If no family history of diagnosed hemochromatosis, check family medical history for symptoms of undiagnosed HH, such as heart disease, early heart attacks especially in men (in their 30's), liver cirrhosis/cancer, diabetes, arthritis, impotence, infertility, chronic fatigue syndrome, etc.
Q: What will a CT/MRI or Ultrasound (US) show?
A: A CT or MRI of the abdomen will only tell you that the liver is very "dense" due to iron content. They do not give you any details such as if there is cirrhosis or not or if there is scar tissue, etc. The density can be measured and it has a very good correlation with the amount of iron in the liver. Both CT and MRI are very good to detect hepatomas (cancerous tumors of the liver) very early and very well. They also help to tell us if they can be surgically removed or not. Ultrasound is another technique that can be used as well and is less expensive than the CT or MRI and uses no radiation like the CT. In fact, an ultrasound with an ACUSON would be advisable in order to maximize any chances of finding an early lesion that might be confined to one lobe and therefore potentially resectable (operable). If you have an "early" stage diagnosis (ferritin less than 500), you probably would not need to have a CT or MRI of the liver, unless liver disease is indicated in some other way.
Q: My doctor says I must have a liver biopsy to confirm a diagnosis of hemochromatosis and won't treat me until I have it. My brother has HH and he didn't have a liver biopsy and began treatment immediately after diagnosis which was successful. What does this mean?
A: A liver biopsy has been used as the "gold standard" by many physicians for decades to confirm a diagnosis of hemochromatosis. It will show your "hepatic iron index" (HII) or how much actual iron is in your liver tissue, a popular storage site for iron in the hemochromatosis patient. In the past, a patient was determined to be a "carrier" or a double gene mutation patient based on how much iron was in their liver. This was, of course, "educated guessing" because a liver biopsy is NOT a genetic DNA test and cannot in any way tell you if you have either of the mutations now known to affect iron metabolism in HH patients. With the advent of the DNA genetic test, doctors are now able to definitively determine a patient's genetic status with or without the liver biopsy, making using the liver biopsy as a means of diagnosis rather obsolete in most cases. The liver biopsy is an invasive procedure and does have morbidity and mortality (injury and death) in a small percentage of procedures. The chance of internal bleeding during or after this procedure has, in some cases, resulted in death of the patient. The advantage of the liver biopsy is that it alone can determine if a patient has cirrhosis of the liver and/or other liver diseases and to what extent. The determination of liver cirrhosis helps the doctor to make a more accurate prognosis for the patient since liver cirrhosis may (not always, but may) lead to liver cancer (hepatoma) at a later date. This prognosis, however, does not alter the treatment plan for HH. Patients with liver cirrhosis can be followed carefully to watch for any medical problems and annually tested with the alpha fetoprotein blood testing to detect early cancer of the liver when it might be surgically removed. The liver biopsy alone is not a good test to detect liver cancer as the sample may be benign but another section of the liver may have a tumor, hence the importance of having an ultrasound, CT, or MRI of the liver to rule out hepatoma in all HH patients. The liver biopsy should be discussed in detail with the physician before deciding to have this procedure done. Also, in the cases of early diagnosis (lower iron levels, no elevated liver enzymes, patient is asymptomatic (no symptoms), young or a child, many physicians now feel that the liver biopsy is not necessary as the liver is probably not damaged and the confirmation of hemochromatosis can be made through the new DNA genetic test. The treatment is the same for the patient whether or not liver cirrhosis is present. The liver biopsy is also an expensive procedure, making it a problem for patients without health insurance.
Q: What are my chances of having liver cancer as a result of having hemochromatosis?
A: If you start phlebotomies before cirrhosis of the liver starts, then the chances of a liver cancer (hepatoma) are not any higher than in the rest of the population. You can detect the beginning of liver cancer by checking the blood periodically with a test called alpha-fetoprotein. Annual or bi-annual ultrasounds of the liver are also advisable in patients with cirrhosis or suspected cirrhosis of the liver. Persons with HH should have the alpha fetoprotein test done two or three times a year. Even in persons without confirmed cirrhosis, the alpha fetoprotein test should be performed just in case. It is an extra security measure. If a hepatoma is found early, it can be removed with a partial liver resection. In some cases, there can be a cure.
Q: Is there a treatment for iron overload?
A: Yes. Hemochromatosis is considered the "Good News Disease" because you can do something about it! There is a treatment--a very easy, simple and effective one! The treatment of choice is bloodletting, medically known as "phlebotomy" (fla-bot-o-me). It is identical to a blood donation at a blood bank. When iron overload is discovered, it is imperative to unload the excess iron as FAST AS SAFELY POSSIBLE by being bled weekly or twice weekly. The patient should try to reduce the serum ferritin to less than 20 within 18 months of diagnosis. The duration of weekly treatments (known as the aggressive treatment phase) will be determined by the amount of iron stored in the body based on blood test results and/or liver biopsy. If the iron overloaded patient is also severely anemic, an iron chelator, Desferal, must be used instead of bleeding. A new oral chelator has been developed called, ExJade, made by Novartis. You can learn more about it at: http://www.exjade.com/index.jsp
Q: If there is a drug I can take for iron overload, wouldn't it be better to use that, instead of giving blood all of the time?
A: Drug chelation (Desferal) for iron overload is not a simple pill or shot that will remove iron from the body. Desferal must be administered through injection or a "pump" over many hours each day and the drug also has side effects. It is also not as effective or as fast as bloodletting/phlebotomy, so those iron overloaded patients who are able to be bled are considered to have a great medical advantage over those who must be treated with the drug. There is a new drug called, ExJade, which is a pill. These methods do have side effects, yet, there is a lot of hope that ExJade, an oral chelator, will gain popularity, especially among those patients with transfusional iron overload and iron loading anemias, who cannot be bled or have therapeutic phlebotomy (bleedletting).
Q: What is the cost of treatment? Will my insurance pay for this?
A: Treatment, known as phlebotomy or bloodletting, which is identical to a blood donation at a blood bank, ranges in cost (in U.S. dollars) per treatment as follows: a.) Blood bank (community blood bank)=$30.00 to $200.00 per treatment b.) Doctor's office=$200.00 to $400.00 per treatment c.) Hospital/outpatient=$400.00 to $1400.00 per treatment You will have to check with your individual insurance company to determine coverage. Although the blood banks are the least expensive, insurance usually does not cover phlebotomy cost at a blood bank (Medicare does not cover blood bank treatments, yet will cover treatment by a doctor), however, it will cover phlebotomy treatment at the much high rates in the doctor's office or hospital. It is odd that insurance would not cover the least expensive procedure and hopefully this will change in the future. The new oral chelator, ExJade, is made by Novartis. Patients interested in more information about ExJade should contact the company and ask about pricing and possible assistance with the cost of the medication.
Q: How often should I be treated?
A: You should have a phlebotomy/bloodletting, at least once a week, as long as your hematocrit remains at 35% or greater before each treatment. Some patients are treated twice a week or even three times a week when severely iron overloaded.
Some patients who have other medical problems, or are elderly, may have their
treatment schedules adjusted to every ten to 14 days initially during the "aggressive"
phase of treatment. When the iron stores are depleted, and the ferritin has reached 20,
then the treatments can be done much less often, 1 to 4 times a year.
Q: How long do I have to have the treatments done?
A: Weekly treatments (the "aggressive treatment phase") should continue as long as your hematocrit remains 35% or greater before each treatment and until your serum ferritin is below 20. At that point, you begin maintenance treatments, about three or four times a year, which should be performed for the rest of your life. The serum ferritin level should be maintained below 20 for the rest of your life. Some patients have reported that when they completed their aggressive phase and were iron depleted that they then stopped and weren't bled again for many years. This is incorrect. You must continue to be bled three or four times a year (the number of times may vary from patient to patient) or the iron stores will build up again placing your health in danger.
Q: How many phlebotomies will I need to have a normal iron level again?
A: The number of phlebotomies varies from patient to patient depending on how high the initial iron overload is. A patient with early diagnosis may only have to give a dozen phlebotomies before going on a maintenance program for life; other patients, in advanced stages of hemochromatosis, may require 80 to 100 phlebotomies or more to "de-iron" themselves ("de-iron" is a term used to denote a patient who has reached a serum ferritin of 20 or a target goal set by his/her physician which is usually a serum ferritin below 150). You can expect each phlebotomy to reduce the ferritin approximately 30 points each time. So, a ferritin of 3000 might require 100 phlebotomies to reach the target goal. A ferritin of 300 might only require 10 phlebotomies to reach the target goal.
Q: My ferritin was 3,000 at diagnosis and was dropping steadily approximately 30 points per treatment, phlebotomy, but suddenly dropped 500 points. My doctor and I don't understand how this could have happened?
A: Serum ferritin is a test which not only determines iron in the body but also inflammation. A body with excess iron is usually inflamed, to varying degrees from patient to patient. As the toxic levels of iron are removed from the body, the inflammation is also reduced, and in some cases, much of the high number in the serum ferritin test reflects inflammation and when the iron is removed, it "relieves" the body of this "irritant" which is reflected in a sudden drop in the ferritin level. It may later even out and drop more steadily, or drop suddenly again on several different occasions. Sudden drops in ferritin do not always happen, however, if they do, it can be considered normal during the treatment of the HH patient.
Q: How will I feel after so many phlebotomies? Are their side effects?
A: The reactions or side effects of phlebotomies differ from patient to patient. For patients who have a history of blood donation in their community, treatment is no different, since it is identical to a blood donation at your local blood bank. The only difference is that it is done more often (weekly) than voluntary blood donation (usually every 56 days) and therefore patients often report being fatigued and weak after numerous treatments, however, they are necessary to prevent damage to the patient or prevent additional damage to the patient, and to prevent death. If you are in "aggressive treatment" (at least weekly) you "may" experience varying degrees of tiredness and fatigue. For advanced patients undergoing vigorous weekly treatments for extended periods of time, some have reported that they have had to stop working or get assistance from family or friends with household chores and child care. Family members and friends should be informed that treatment is necessary to save the patient's life and understand that physical and emotional support are essential for the patient's successful completion of initial treatment. Other patients actually report feeling "invigorated" after each treatment with a few days of tiredness after each treatment and then back to normal. Be sure to discuss any side effects that you experience with your physician.
Q: Is hemochromatosis reversible through phlebotomy or must a patient undergo phlebotomy on a regular basis for the rest of his life? Does phlebotomy eventually ease the symptom so that this treatment may stop?
A: The symptoms of iron overload/hemochromatosis sometimes can be improved or even reversed (i.e., a woman infertile from hemochromatosis and told to adopt a child was diagnosed, treated and now has a biological child). Treatment, however, should continue, for the rest of the patient's life, usually at a rate of three or four phlebotomies per year, although this rate can differ slightly from patient to patient. Aggressive, weekly phlebotomy will eventually remove the stored iron in the body, however, the iron will once again accumulate if regular phlebotomy is not maintained for the rest of the patient's life. Remove that stored iron as safely and quickly as possible and keep it out with regular phlebotomy for the rest of your life! Remember, once you are "de-ironed", don't stop! Bloodletting is for life and if you don't regularly have blood removed, the iron will simply build up again and store in vital organs. Note: if iron overload is due to "acquired hemochromatosis" through iron pill ingestion for instance, then once deironed, the treatments can stop permanently.
Q: I have a fear of needles; isn't there any other way to be treated?
A: First of all, if you have a fear of needles, you are not alone. Phlebotomy (bloodletting) is the safest and most effective way to treat iron overload and prevent the damage and premature death of the patient. Phlebotomy is much more effective than drug treatment which is cumbersome and has side effects. Yes, there are needles, but there are some "tricks" that you can use. Some nurses use lidocaine on the arm (EMLA creme) before the procedure to make needle insertion more comfortable; some patients put hot compresses on the arm to help make it more "ready" for the treatment followed by a cold pack afterwards; others put vitamin E on the arm where the needle will go several hours before the procedure (do this to both arms since you don't know each time which arm will be used).
Getting a phlebotomist (nurse or person who does the bloodletting procedure) with whom you can work well and feel comfortable is very important, too. If you find such a person, request him/her each time, learn their schedule, and you will probably have a better experience with your treatment. If a nurse or technician makes you feel uncomfortable, physically or mentally, then get someone else if at all possible. You want to be relaxed for the procedure. There is also a "butterfly" needle which some patients have reported as much more comfortable than the regular needles used for blood donation. Ask questions and use these suggestions, it will make it much easier in the long run.
All in all, you will get "used" to the weekly bloodletting and find that usually it is just as simple as donating a unit of blood. And, remember, phlebotomies certainly are preferable to the alternative--organ damage and serious health conditions (which involve many needles), not to mention premature death, that would result from no treatment at all. Discuss your fears with your physician and the phlebotomist so that they can work with you to make this experience as comfortable and pleasant as possible. If your fear of needles and/or blood is extreme, some patients have been able to comply using sedatives and tranquilizers prior to the procedure. Remember, this procedure is identical to a blood donation, a common, everyday medical procedure performed by many community minded citizens around the country on their "lunch break". Most patients do not have any problems or unusual fears concerning this procedure, but if you do have a great fear, it is imperative that the medical team know about it so that you can work out a plan that will allow you to be treated. And, remember, you are not alone in your fear of needles, which is very common. Compliance with the treatment plan is essential for a good outcome. Many patients who have had a fear of needles, have overcome this fear and completed their treatments successfully and gone on to counsel other patients who feel as they used to about the treatment! Remember, if you DON'T get treated, you will have far more needles than you could imagine from the resulting illnesses such as diabetes, liver transplant, etc. The sooner you start treatment, the fewer phlebotomies you will need overall. The prescription should read: "Dx: Hemochromatosis--Phlebotomize patient as long as hct. is greater than 35%" This prescription should be good for one year and renewed annually.
Q: Is the blood I give during my treatment used as donor blood? The blood bank said they were going to discard it? Is there something wrong with my blood? I thought HH wasn't a "blood disease" or infectious?
A: Some blood banks do use the hemochromatosis blood as donor blood, but most blood banks in the U.S. do not. There is nothing wrong with hemochromatosis blood; HH is not a blood disease, nor is it infectious. HH blood can be used as donor blood as long as it meets the standards and tests of the blood bank (i.e. free from HIV, hepatitis, etc.). HH blood is not contagious or infectious in any way. The FDA was petitioned by the late Victor Herbert, MD JD, of Mt. Sinai School of Medicine in New York City, NY, to use hemochromatosis blood as donor blood. Although the FDA did not immediately change their policy, more petitions followed. In the past, the blood bank was using what many consider to be an "outdated" policy which says that any patient who gives blood for a "medical reason" is a "motivated donor" and they feel that motivated donors' blood is not as "safe" as other blood donations because donors might donate (in order to save their own lives due to the medical condition) when they personally know that they shouldn't (i.e. they have HIV, hepatitis, etc.). The blood bank feels that people who are "motivated donors" will not tell them about HH so that they can donate blood for free to avoid the cost of phlebotomies.
Leading doctors around the country have urged the AABB and the Red Cross to change their policies concerning HH patients, who are shown to be just as safe as the general public when donating blood. In 1999, the FDA approved the use of hemochromatosis blood as donor blood. Any blood bank can apply for a "variance" to use HH blood as donor blood. The FDA did not issue a mandate that all blood banks had to use HH blood as donor blood, but did give them the option to do so if they decided to do so. More than fifty blood banks around the USA accept and use HH blood as donor blood. If you want your local blood bank to use HH blood as donor blood, you can contact the blood bank director and discuss how their policy might be changed in the future. You can find a list of these blood banks on the AHS web site or the FDA web site (www.fda.org) . Of course, there are many patients who have hemochromatosis and know it and who donate blood without telling the blood bank. There are also many patients who have hemochromatosis and don't know it and are donating blood to the blood bank. Most blood banks do not test donors for iron overload or hemochromatosis. The American Hemochromatosis Society feels that HH patients are very "special" since they are "super donors".
Q: Is there a special diet I should eat or foods I should avoid?
A: Basically, iron in the diet is not going to make much difference in relation to your treatment, however, it is wise to check the labels of processed foods for their iron content. For instance, certain breakfast cereals contain 100% RDA of iron as do other products. Avoid alcohol and vitamin C which enhance iron absorption, cooking in cast iron cookware, and never take iron pills or supplements containing iron. Hemochromatosis patients should not eat raw seafood or shellfish (cooked is fine) due to a bacteria (vibrio vulnificus) which can kill the patient within hours of ingestion (due to a compromised liver which many HH patients have) unless emergency treatment of antibiotics (tetracycline) is administered. (Note: this can also happen to fishmen who handle and clean fish). Drink tea and coffee with your meals which will help block the iron in the foods you do eat. For more details on diet, you can purchase "The Hemochromatosis Cookbook" by Cheryl Garrison available through any major book store, amazon.com, or the Iron Disorders Institute (IDI).
Q: Is iron overload/hereditary hemochromatosis "curable"?
A: Iron Overload is not curable if it is genetic hemochromatosis, hereditary hemochromatosis (HH). The patient will need to be monitored and treated for the rest of his/her life. However, iron overload is curable in the case of acquired hemochromatosis such as massive doses of iron pills, etc. Once the patient is "de-ironed", he/she will not need to be treated anymore. For HH, we hope that research in the future will find a cure for this condition, until then, treatment and early diagnosis, offer the next best thing to a cure. In fact, HH can be prevented with early genetic screening and detection of the high risk gene mutations. In such cases, patients can be genetically screened, identified, and monitored, so that they will never have high iron at any time in their lives, thusly preventing organ damage and premature death. Of course, someday, we hope that there will be a complete cure for hereditary hemochromatosis.
Q: If hemochromatosis is a genetic disease, should other family members be tested? Which ones and when?
A: ALL blood relatives (not just the immediate family) of the iron-overloaded individual should be strongly warned to be screened immediately with the iron profile of serum iron, TIBC, and serum ferritin) and the new DNA genetic test. All should be monitored annually for the rest of their lives. This includes men, women (pre and post menopausal) and minor children. If the HH patient has children, the spouse should also be tested. Actually, everyone in our society should be tested, but especially family members. Due to the lack of public awareness and physician education about hemochromatosis, most family members are not screened and many diagnoses are missed as a result.
Q: I told my family members that I had hereditary hemochromatosis and what tests to have done, but they won't listen to me; they say that their own doctors tell them "not to worry". I am worried; what can I do?
A: Family compliance with screening is often very challenging to the first member of the family to be tested. Try to find several members who are willing to have the DNA test at least. If those tests are confirmed, often other members will take new "interest" and comply when they see the DNA test results in black and white. Another possible tactic is to have your doctor contact your family members' doctors, either by telephone and/or letter and urge their doctors to screen them with the proper blood tests and DNA tests. Another possible tactic is to obtain DNA test kits from a lab and mail them to family members or bring the kits to a family reunion, wedding, holiday gathering, and distribute them at that time and explain the importance of the test. Finally, if the family members have children, urge them to have the DNA testing if not for themselves, to do it for the sake of their children. People often will be tested when their children's and grandchildren's health is at stake. Home testing is also another way to encourage family members to be tested. By genetically testing family members at home, and avoiding the medical setting of the doctor's office, many family members will be tested. We recommend HealthCheckUSA (www.healthcheckusa.com) for genetic testing. It is fast, simple, and painless. A DNA test kit can be mailed directly to your home and is suitable for adults, children, and infants.
Q: My pediatrician says I don't need to worry about my children between the ages of 2 years and 18 years old having iron overload. He says it's an "adult onset" disease; is this true?
A: No! Pediatric hemochromatosis is very real and more and more cases are being identified every day. Sandra Thomas, President of the American Hemochromatosis Society, has founded the "Children HHelping Children" Screening & Awareness Project to screen, diagnose, and treat children under the age of 18 years with iron overload/hereditary hemochromatosis. All children should have the DNA test ideally at birth to ascertain their possible risk for HH and also have the TS and serum ferritin tests after the age of two years to see if they are clinically iron overloaded at that current time. If necessary, phlebotomy treatment should be started in the child if he/she is loading too much iron, but you should make sure you are using a doctor who is familiar with pediatric hemochromatosis. Children with iron overload often have cardiac symptoms as well as liver disease. They have high saturations and fairly normal serum ferritin readings. More research is needed to establish standardized protocols for pediatric hemochromatosis, but it is imperative that you know your child's genetic risks for HH to make sure that your child can have a normal life expectancy through preventive measures. Some of these cases may be "juvenile hemochromatosis". Only an expert in hemochromatosis will be able to truly identify the children at risk and those who have developed the disease during childhood. Liver biopsies are not recommended for children unless evident liver disease is present. A non invasive test with a ferritometer can measure the amount of iron in the liver if this measurement is needed.
Q: If I have the double gene mutation (homozygous) for hemochromatosis but am not clinically iron overloaded (have high iron levels on lab results) at this time, can I develop iron overload later, such as in 2, 5, or 10 or more years later?
A: Yes, patients with the double gene may develop iron overload at some later time in their lives, therefore, they should be annually monitored by their physician for transferrin saturation and serum ferritin. It is important to note that anyone can develop clinical iron overload, whether they have one, two, or no mutations for HH.
Q: If I have the single gene mutation (heterozygote) and am a "silent carrier" for hemochromatosis, will I become iron overloaded?
A: Most carriers do not become ill (have symptoms or elevated iron levels) during their lifetime, however, they should avoid the same things that the double gene person does. Carriers are at higher risk than non-carriers for loading excess iron and can become iron overloaded so they should be annually monitored by their physicians. Carriers of the single mutation, known as "silent carriers" should also refrain from heavy alcohol consumption and/or massive vitamin C supplementation (you may drink orange juice but do not take mega doses of vitamin C pills), and vitamins containing iron. Single gene carriers are at risk of loading high iron and should annually monitor their iron levels with serum iron, TIBC, and serum ferritin tests.
Q: No one in my family has ever been diagnosed with hemochromatosis or had any of the symptoms; how could I possibly have this disease?
A: Many patients who have full blown hemochromatosis (the double gene mutation/homozygote) have family members who have it also but do not know it or who have died from hemochromatosis but it was never diagnosed as iron overload. Also, it is possible that all of the family members in the family (living or deceased) have also been asymptomatic single gene mutation "silent carriers", lived to old age and no one had the double gene until you, the double mutation patient, were born and your diagnosis of the double gene mutation was discovered. Therefore, those people who say they are the "only" member of the family are incorrect. There are definitely carriers in the family, all double gene patients' mothers and fathers MUST have been at least single gene/heterozygote carriers, and either or both parents could be double gene/homozygotes as well. Many patients ask if they got HH from their mother's or father's side of the family. The answer is that they got it from BOTH sides of the family; HH is an autosomal recessive mutation, therefore, you must inherit one mutated gene from your mother and one from your father, for you to have the double mutation. Many families are startled to learn after an initial diagnosis in that family, that many other family members also have HH! If both parents are double gene, then all of their children will also have the double gene.
Q: I had the DNA test and found out that I have the double gene mutation. My husband, who has always been in good health, was tested and we were shocked to learn that he is a "silent carrier" of the single HH gene. We know now that our four children have inherited various combinations of our HH genes from us; two now have been diagnosed with hemochromatosis and two are also silent carriers. Now all of our young grandchildren are being DNA tested by their pediatricians. We feel very guilty about passing these genes on to our children and grandchildren...do others feel this way, too?
A: As we proceed into an era of genetic testing, it is important to remember that NO ONE is free of genetic defects. In fact, we can estimate at this time that everyone has at least three or four genetic defects which may or may not manifest during our lifetimes. As genetic testing becomes more "mainstream" more and more people, like you, will learn what their genetic status is for various genetic diseases. When you consider that people for many generations have died of diabetes, cancer, etc., we can assume that many of these cases were actually due to a gene carried in the family or a "genetic predisposition" for a particular disease that has been passed from generation to generation. Genetic testing is no longer in the realm of "science fiction" and is quickly becoming a powerful tool for doctors to monitor patients and provide therapies which may delay, or even prevent, as in the case of HH, lethal symptoms of a disease. The good news is that hereditary hemochromatosis is a genetic disease whose symptoms, organ damage, and premature death can be completely prevented! Therefore screening and early diagnosis are the keys to full life expectancy! You have nothing about which to feel guilt; you are getting your family members screened; and, if appropriate, into treatment. By becoming educated about hereditary hemochromatosis, you are saving lives--now and for generations to come!
Q: My family and friends have never heard of hereditary hemochromatosis and my doctor admits he knows little about it. Why doesn't anyone know anything about HH if it is so common? I feel all alone.
A: Although it is the most common genetic disease in the U.S.A., because there is no routine screening for HH at this time, most cases go undiagnosed. HH is all around you--your families and your friends--they just don't know it. You can help increase awareness in your family, in your community and save lives yourself. You can encourage your doctor to attend read the AHS web page and to attend HH symposiums and CME seminars held around the country. You are not alone; there are thousands of HH patients all over the country who feel as you do. If you have a computer, you can link up with other HH patients via the Internet or the online discussion group, "Families HHelping Families" on the AHS web site.
Q: What is the American Hemochromatosis Society (AHS) and what is its mission?
A: The American Hemochromatosis Society (AHS) is the leading non profit organization for information on genetic testing for iron overload/hereditary hemochromatosis, and information and support for pediatric hereditary hemochromatosis. AHS was founded on March 30, 1998 by Sandra Thomas, a carrier of the HH mutation and whose mother, Josephine Bogie Thomas, was a victim of HH and was diagnosed in 1983 and died from complications of the disease on May 13, 1999. AHS originally was based in Delray Beach, Florida, and is now based in Lake Mary, near Orlando, Florida. It is a 501(c)3 non-profit organization whose mission is to ban genetic discrimination, promote genetic testing for HH of the American population, and emphasize a focus on pediatric hereditary hemochromatosis and neonatal hemochromatosis. More than 1.5 million Americans who have iron overload/hereditary hemochromatosis and another 32 million Americans who are "silent carriers" of the single mutation, will need to be served with information and support...AHS will be there for them. AHS serves both physicians and patients.
Q: Are there any books about iron overload that AHS offers?
A: Yes! A list of books on HH by various authors appears on the AHS web page and AHS president, Sandra Thomas, is currently writing a book about hereditary hemochromatosis. An educational slide presentation and video are in production. AHS also has free educational materials which can be mailed to patients and their families. Please send a self addressed business envelope with two stamps.
Q: How can I get more information from the American Hemochromatosis Society (AHS) on iron overload/hemochromatosis by email and the Internet?
A: You can email Sandra Thomas, President, American Hemochromatosis Society, at: mail@americanhs.org The web page address is: www.americanhs.org AHS has it's own discussion group called, "Families HHelping Families". See the web site for more information on how to join this group.
Q: How can I get more information from AHS on iron overload/hemochromatosis by mail? How can I make a donation to AHS?
A: For free information by mail write to the AHS directly (Please, enclose a self-addressed envelope with two stamps):
American Hemochromatosis Society, Inc. (AHS) (non-profit)
Sandra Thomas, President/Founder,
4044 W. Lake Mary Blvd., #104, PMB 416,
Lake Mary, Florida 32746-2012 USA
Telephone: 407-829-4488
Toll-free Info Line: 1-888-655-IRON (4766)
(Due to the volume of mail, please allow four to six weeks for delivery)
If you would like to make a memorial donation or a donation in someone's honor, please indicate that information with your donation. AHS is a 501c3 non profit organization and all donations are gratefully received. Please make your check payable to: AHS.
http://www.americanhs.org/faq.htm
Please note: This information has been compiled with the advice of leading doctors/researchers as well as HH patients themselves. This information is based on the following premise that this is the information we would give to a family member, where "money was no object", and the latest information on health options was wished. Through this premise, the most thorough and aggressive health care can be suggested. Each patient should confer with his/her physician about their own health care. If a physician does not regularly treat HH patients, he/she should consult with a medical expert. AHS can provide such experts. Sandra Thomas, President, American Hemochromatosis Society
Q: What is iron overload, hemochromatosis?
A: Hemochromatosis (pronounced: He-mo-chro-ma-toe-sis) is a genetic condition of abnormal iron metabolism that permits absorption of too much iron from an ordinary diet. Hereditary hemochromatosis is an autosomal recessive disorder. It is NOT a blood disease. It is also known as iron overload or iron storage disease. It is possible for someone who has never had an iron pill in his/her life to have iron overload.
Q: Can iron overload be acquired?
A: Yes, iron overload can be acquired. The genetic form is known as primary hemochromatosis, hereditary hemochromatosis (HH) or (HHC), or genetic hemochromatosis (GH) and idiopathic hemochromatosis (from an unknown origin), a term which is rarely used anymore. The acquired form (through massive doses of iron pills or blood transfusions) is known as secondary hemochromatosis, acquired hemochromatosis, or transfusional iron overload.
Q: How common is iron overload/hemochromatosis?
A: Frequency (incidence in the general population) of the abnormal gene is: 1 in 100-200 people has hemochromatosis (double gene mutation known as a homozygote) and 1 in 8-10 people is a carrier of hemochromatosis (single gene mutation known as a heterozygote or "het" for short). That's approximately 32 million Americans who are carriers and 1.5 million Americans have the double gene which can lead to full blown hemochromatosis. Recent studies in Ireland, show a frequency of 1 in 4 as carriers of the single mutation and 1 in 64 as double gene mutation. Because of this high frequency, routine screening for hereditary hemochromatosis is medically indicated.
Q: Who is affected by iron overload/hemochromatosis?
A: Most affected people DO NOT KNOW they are accumulating dangerous stores of iron. Tragically underdiagnosed, no race, age, or gender is immune. (Premenopausal women do have iron overload as well as young children) The American Hemochromatosis Society (AHS) has made an official position statement and issued guidelines for diagnosis, treatment, and management of iron overload/hereditary hemochromatosis, including recommendations that all Americans age 2 years and older be routinely and universally screened for iron overload as well as genetic screening. All ethnic groups can be affected, but those with an Irish/Scottish/Celtic/British heritage have an even higher prevalence of the HH mutation. Hispanics and Afro Americans also have iron overload.
Q: How serious is iron overload, hemochromatosis?
A: The excess iron injures body organs and KILLS unless detected in time for adequate iron storage removal. It is a very serious disease, but quite benign if detected early before organ damage has occurred. That is why routine screening is so important. HH is a lethal but treatable disease. Don't let anyone tell you that iron overload/HH is "nothing to worry about". The higher the ferritin level, the potential for serious organ damage is increased. An early diagnosis offers the patient a normal life span.
Q: Is there anything that can be done to treat or prevent iron overload?
A: Yes. Hereditary hemochromatosis is one of the few genetic diseases which has a prevention plan so that all organ damage and premature death can be completely prevented. When the excess iron IS detected EARLY and is ADEQUATELY removed, the individual can enjoy a normal life span in normal health. The motto of the American Hemochromatosis Society is: "Prevention through Genetic Testing".
Q: What are the symptoms of iron overload, hemochromatosis?
A: Patients can have iron overload and NOT have symptoms (asymptomatic) and that is the best time to diagnose the patient. Many doctors have been taught to look for "signs and symptoms" of HH but by the time symptoms appear, it is often too late to save the patient's life. Iron overload and storage in vital body organs can damage and may cause:
chronic fatigue (the most common complaint by patients);
cirrhosis/cancer of the liver (with or without a history of alcohol use);
arthritis/joint pain;
impotence/sterility/infertility; early menopause/irregular menses;
hair loss; hair thinning
diabetes (bronze diabetes, a darkening, graying of the skin not caused by sun exposure);
cancer (cancer thrives on iron); (especially primary liver cancer)
abdominal pain/swelling;
weight loss;
frequent colds/flu/infections, compromised immune system;
headaches;
hypothyroidism; (low thyroid)
heart irregularities/heart failure/heart attack (especially in younger men);
cirrhosis of the liver (with or without a history of alcohol use);
hepatoma/liver cancer (the leading cause of death in HH);
premature death.
Anyone with any combination of these symptoms, or a family history of these symptoms, should be tested for HH immediately. But remember, two important facts:
1.) There can be numerous generations of "silent carriers" of the mutation who never become ill and live to old age thereby giving a "false security" that HH doesn't "run in the family"
2.) Some patients do not have symptoms until they are end stage and their lives cannot be saved. Early detection should be achieved through:
1.) Knowledge of genetic risk through DNA Testing
2.) Annual screening with serum iron, TIBC, and serum ferritin to assure that iron storage is not taking place.
Q: I went to the blood bank and they told me I was anemic; how could I have iron overload at the same time?
A: Blood banks do NOT screen for iron overload/hemochromatosis. They are basing their comments on the hematocrit or hemoglobin readings that they take prior to a blood donation (the finger prick test) and these are not the correct tests for iron overload storage! Yet blood banks continue to give out false information to their clients, telling them that they have low "iron" or even in some cases that their iron is high! The iron-overloaded person may be anemic at the same time. There are several types of anemia that are iron-loading! Hematocrit and hemoglobin are NOT tests for iron overload/hemochromatosis; ask your physician to test you with transferrin saturation (TS) which is calculated by dividing the serum iron by the TIBC (total iron binding capacity) and serum ferritin to confirm or rule out iron overload.
Q: How can I know if I have iron overload/hemochromatosis? What tests should be performed? I hear that there is a DNA genetic test kit for hemochromatosis, is that true?
A: A simple series of blood tests which can be performed by any doctor or lab can indicate iron levels. They must be proper iron measures: Total Iron Binding Capacity (TIBC) together with Serum Iron. Divide TIBC into Serum Iron to get the percentage of transferrin saturation. It is important that the serum ferritin is also performed at the same time and it should be done, if possible, while fasting. Refrain from iron pills for a week prior to the tests. A new test, serum ferritin-iron assay will also be available in the near future. The discovery of the hemochromatosis gene was announced in August 1996 by Mercator Genetics Inc. of Menlo Park, California (which was purchased by Progenitor in 1997. Bio-Rad Laboratories of Hercules, CA bought the patent from Progenitor. Bio-Rad currently holds the patent to the HFE mutation). The new genetic DNA test (HLA-H now known as HFE or HFe) has been commercially commercially available from many labs around the nation since 2/1997, including SmithKline Beecham Clinical Laboratories currently known as Quest Diagnostics on a nationwide basis. Many university labs and other smaller independent genetics labs across the nation now offer the DNA testing for HH. In the early years, many of them only tested for the one mutation (845A also known as Cys282tyr), but today most labs test for BOTH HH mutations (845A and 187G also known as cys282 and his63). There is a 3rd gene mutation, 65S, but it is not included in most labs' testing protocols. Several labs also test for both gene mutations and offer a handy "cheek brush" tissue collection kit which you can get through the mail and perform in the privacy of your own home: Kimball Genetics in Denver, Colorado (1-800-320-1807 or 303-320-1807 in Denver or outside of the U.S.A.) The "cheek brush" method (no needles/blood/pain) is great for kids and adults. More info on how to order these tests is available from the AHS office at 407-829-4488. If you wish to get genetic DNA testing without using a doctor or having the results on your medical records, you may contact HealthCheckUSA (www.healthcheckusa.com) or call on their toll free number: 1-800-929-2044, to order the Kimball Genetics Lab DNA test kit. The results are private and confidential and are mailed directly to the patient, thusly protecting the patient's medical information. You may contact the lab directly for current prices. Genetic counselors are available to patients as part of the cost of the testing. The American Hemochromatosis Society strongly urges patients and their family members (male and female) to be genetically tested, including children, teens, young adults and seniors. If you have a question about your genetic testing, feel free to contact the AHS office directly for more information.
Q: I had the blood tests for iron overload and my doctor says I am "fine"; do I need to worry about it now?
A: First of all, always get copies of your medical lab reports for your home medical file and review them yourself. Make sure that the serum iron, TIBC, and serum ferritin tests are on the report and double check to make sure that you fall into the "safe zone" set by AHS--a ferritin under 150 and a saturation percentage of under 40%. Some labs have very "high" normal levels and you might not really be in a safe zone. Many patients have contacted us who have iron studies in the "danger zone" but their doctors have told them that they are fine. It is prudent to find out for yourself. The same philosophy applies to the DNA test--make sure you get copies of the report for your own files and know if you have the single or double mutation and which of the two mutations you carry (you can even carry one of each mutation which would make you known as a compound heterozygote).
Q: I've had the iron profile tests, read them myself and they were within the normal range; do I need to be retested ever again and/or have the DNA genetic test, especially since I feel fine?
A: Yes. Even if your first test was negative, ideally, you should be monitored annually by your physician. Also, by having the DNA test, you can discover if you have the single or double gene for hemochromatosis and determine your risk factor of developing full blown hemochromatosis or passing a mutation to offspring. A very small percentage (about 12% to 15%) of patients who are clinically iron overloaded (have high TS and serum ferritin levels) may have a negative result on the genetic test. Scientists believe that these persons have still another HH mutation (which has yet to be discovered and a test for it developed) which is causing this iron storage. For this reason, it is always wise to test using the transferrin saturation and serum ferritin annually to be on the safe side.
Q: What iron levels are considered "suspicious" for iron overload/hemochromatosis?
A: A percent of saturation of more than 40% and/or a serum ferritin of more than 150 are considered suspicious for iron overload/hemochromatosis. It is important to note that in some patients, the percent of saturation can be quite high while the ferritin rather low (this is often the case in children or young adults in their 20's) or conversely, with normal percent of saturation and a high serum ferritin. Genetic testing can, in most cases, confirm the diagnosis so that treatment can begin. Ask your doctor about liver function tests, if these are also elevated, that is another possible sign of HH.
Q: How is a diagnosis for iron overload/hemochromatosis confirmed?
A: Confirmation of a diagnosis is based on a combination of several factors; these will vary from doctor to doctor on which ones are used:
a.) Elevation of iron tests such as transferrin saturation and serum ferritin
b.) Elevation of liver enzymes (abnormal liver function tests)
c.) Symptoms (diabetes/heart disease/arthritis/impotence/infertility/bronzed skin, liver disease)
d.) Liver biopsy showing hepatic iron index (HII) and such liver diseases as cirrhosis/cancer
e.) DNA genetic test (results are available between 1 to 14 days depending on the lab used)
f.) CT/MRI/Ultrasound of the liver showing deposition of iron in the liver or hepatoma(s) (liver tumors).
g.) Quantitative phlebotomy (a trial series of six weekly phelobotomies to confirm diagnosis; if the hematocrit remains 35% or greater immediately prior to each phlebotomy. Six weeks of weekly bloodletting is another way to confirm iron overload, hemochromatosis)
h.) Alpha Fetoprotein bloodwork ruling out liver cancer due to HH.
i.) EKG to rule out heart damage from HH.
j.) Family history of iron overload, especially parents/siblings, who should also be screened with transferrin saturation and serum iron and genetic tests for comparison. If no family history of diagnosed hemochromatosis, check family medical history for symptoms of undiagnosed HH, such as heart disease, early heart attacks especially in men (in their 30's), liver cirrhosis/cancer, diabetes, arthritis, impotence, infertility, chronic fatigue syndrome, etc.
Q: What will a CT/MRI or Ultrasound (US) show?
A: A CT or MRI of the abdomen will only tell you that the liver is very "dense" due to iron content. They do not give you any details such as if there is cirrhosis or not or if there is scar tissue, etc. The density can be measured and it has a very good correlation with the amount of iron in the liver. Both CT and MRI are very good to detect hepatomas (cancerous tumors of the liver) very early and very well. They also help to tell us if they can be surgically removed or not. Ultrasound is another technique that can be used as well and is less expensive than the CT or MRI and uses no radiation like the CT. In fact, an ultrasound with an ACUSON would be advisable in order to maximize any chances of finding an early lesion that might be confined to one lobe and therefore potentially resectable (operable). If you have an "early" stage diagnosis (ferritin less than 500), you probably would not need to have a CT or MRI of the liver, unless liver disease is indicated in some other way.
Q: My doctor says I must have a liver biopsy to confirm a diagnosis of hemochromatosis and won't treat me until I have it. My brother has HH and he didn't have a liver biopsy and began treatment immediately after diagnosis which was successful. What does this mean?
A: A liver biopsy has been used as the "gold standard" by many physicians for decades to confirm a diagnosis of hemochromatosis. It will show your "hepatic iron index" (HII) or how much actual iron is in your liver tissue, a popular storage site for iron in the hemochromatosis patient. In the past, a patient was determined to be a "carrier" or a double gene mutation patient based on how much iron was in their liver. This was, of course, "educated guessing" because a liver biopsy is NOT a genetic DNA test and cannot in any way tell you if you have either of the mutations now known to affect iron metabolism in HH patients. With the advent of the DNA genetic test, doctors are now able to definitively determine a patient's genetic status with or without the liver biopsy, making using the liver biopsy as a means of diagnosis rather obsolete in most cases. The liver biopsy is an invasive procedure and does have morbidity and mortality (injury and death) in a small percentage of procedures. The chance of internal bleeding during or after this procedure has, in some cases, resulted in death of the patient. The advantage of the liver biopsy is that it alone can determine if a patient has cirrhosis of the liver and/or other liver diseases and to what extent. The determination of liver cirrhosis helps the doctor to make a more accurate prognosis for the patient since liver cirrhosis may (not always, but may) lead to liver cancer (hepatoma) at a later date. This prognosis, however, does not alter the treatment plan for HH. Patients with liver cirrhosis can be followed carefully to watch for any medical problems and annually tested with the alpha fetoprotein blood testing to detect early cancer of the liver when it might be surgically removed. The liver biopsy alone is not a good test to detect liver cancer as the sample may be benign but another section of the liver may have a tumor, hence the importance of having an ultrasound, CT, or MRI of the liver to rule out hepatoma in all HH patients. The liver biopsy should be discussed in detail with the physician before deciding to have this procedure done. Also, in the cases of early diagnosis (lower iron levels, no elevated liver enzymes, patient is asymptomatic (no symptoms), young or a child, many physicians now feel that the liver biopsy is not necessary as the liver is probably not damaged and the confirmation of hemochromatosis can be made through the new DNA genetic test. The treatment is the same for the patient whether or not liver cirrhosis is present. The liver biopsy is also an expensive procedure, making it a problem for patients without health insurance.
Q: What are my chances of having liver cancer as a result of having hemochromatosis?
A: If you start phlebotomies before cirrhosis of the liver starts, then the chances of a liver cancer (hepatoma) are not any higher than in the rest of the population. You can detect the beginning of liver cancer by checking the blood periodically with a test called alpha-fetoprotein. Annual or bi-annual ultrasounds of the liver are also advisable in patients with cirrhosis or suspected cirrhosis of the liver. Persons with HH should have the alpha fetoprotein test done two or three times a year. Even in persons without confirmed cirrhosis, the alpha fetoprotein test should be performed just in case. It is an extra security measure. If a hepatoma is found early, it can be removed with a partial liver resection. In some cases, there can be a cure.
Q: Is there a treatment for iron overload?
A: Yes. Hemochromatosis is considered the "Good News Disease" because you can do something about it! There is a treatment--a very easy, simple and effective one! The treatment of choice is bloodletting, medically known as "phlebotomy" (fla-bot-o-me). It is identical to a blood donation at a blood bank. When iron overload is discovered, it is imperative to unload the excess iron as FAST AS SAFELY POSSIBLE by being bled weekly or twice weekly. The patient should try to reduce the serum ferritin to less than 20 within 18 months of diagnosis. The duration of weekly treatments (known as the aggressive treatment phase) will be determined by the amount of iron stored in the body based on blood test results and/or liver biopsy. If the iron overloaded patient is also severely anemic, an iron chelator, Desferal, must be used instead of bleeding. A new oral chelator has been developed called, ExJade, made by Novartis. You can learn more about it at: http://www.exjade.com/index.jsp
Q: If there is a drug I can take for iron overload, wouldn't it be better to use that, instead of giving blood all of the time?
A: Drug chelation (Desferal) for iron overload is not a simple pill or shot that will remove iron from the body. Desferal must be administered through injection or a "pump" over many hours each day and the drug also has side effects. It is also not as effective or as fast as bloodletting/phlebotomy, so those iron overloaded patients who are able to be bled are considered to have a great medical advantage over those who must be treated with the drug. There is a new drug called, ExJade, which is a pill. These methods do have side effects, yet, there is a lot of hope that ExJade, an oral chelator, will gain popularity, especially among those patients with transfusional iron overload and iron loading anemias, who cannot be bled or have therapeutic phlebotomy (bleedletting).
Q: What is the cost of treatment? Will my insurance pay for this?
A: Treatment, known as phlebotomy or bloodletting, which is identical to a blood donation at a blood bank, ranges in cost (in U.S. dollars) per treatment as follows: a.) Blood bank (community blood bank)=$30.00 to $200.00 per treatment b.) Doctor's office=$200.00 to $400.00 per treatment c.) Hospital/outpatient=$400.00 to $1400.00 per treatment You will have to check with your individual insurance company to determine coverage. Although the blood banks are the least expensive, insurance usually does not cover phlebotomy cost at a blood bank (Medicare does not cover blood bank treatments, yet will cover treatment by a doctor), however, it will cover phlebotomy treatment at the much high rates in the doctor's office or hospital. It is odd that insurance would not cover the least expensive procedure and hopefully this will change in the future. The new oral chelator, ExJade, is made by Novartis. Patients interested in more information about ExJade should contact the company and ask about pricing and possible assistance with the cost of the medication.
Q: How often should I be treated?
A: You should have a phlebotomy/bloodletting, at least once a week, as long as your hematocrit remains at 35% or greater before each treatment. Some patients are treated twice a week or even three times a week when severely iron overloaded.
Some patients who have other medical problems, or are elderly, may have their
treatment schedules adjusted to every ten to 14 days initially during the "aggressive"
phase of treatment. When the iron stores are depleted, and the ferritin has reached 20,
then the treatments can be done much less often, 1 to 4 times a year.
Q: How long do I have to have the treatments done?
A: Weekly treatments (the "aggressive treatment phase") should continue as long as your hematocrit remains 35% or greater before each treatment and until your serum ferritin is below 20. At that point, you begin maintenance treatments, about three or four times a year, which should be performed for the rest of your life. The serum ferritin level should be maintained below 20 for the rest of your life. Some patients have reported that when they completed their aggressive phase and were iron depleted that they then stopped and weren't bled again for many years. This is incorrect. You must continue to be bled three or four times a year (the number of times may vary from patient to patient) or the iron stores will build up again placing your health in danger.
Q: How many phlebotomies will I need to have a normal iron level again?
A: The number of phlebotomies varies from patient to patient depending on how high the initial iron overload is. A patient with early diagnosis may only have to give a dozen phlebotomies before going on a maintenance program for life; other patients, in advanced stages of hemochromatosis, may require 80 to 100 phlebotomies or more to "de-iron" themselves ("de-iron" is a term used to denote a patient who has reached a serum ferritin of 20 or a target goal set by his/her physician which is usually a serum ferritin below 150). You can expect each phlebotomy to reduce the ferritin approximately 30 points each time. So, a ferritin of 3000 might require 100 phlebotomies to reach the target goal. A ferritin of 300 might only require 10 phlebotomies to reach the target goal.
Q: My ferritin was 3,000 at diagnosis and was dropping steadily approximately 30 points per treatment, phlebotomy, but suddenly dropped 500 points. My doctor and I don't understand how this could have happened?
A: Serum ferritin is a test which not only determines iron in the body but also inflammation. A body with excess iron is usually inflamed, to varying degrees from patient to patient. As the toxic levels of iron are removed from the body, the inflammation is also reduced, and in some cases, much of the high number in the serum ferritin test reflects inflammation and when the iron is removed, it "relieves" the body of this "irritant" which is reflected in a sudden drop in the ferritin level. It may later even out and drop more steadily, or drop suddenly again on several different occasions. Sudden drops in ferritin do not always happen, however, if they do, it can be considered normal during the treatment of the HH patient.
Q: How will I feel after so many phlebotomies? Are their side effects?
A: The reactions or side effects of phlebotomies differ from patient to patient. For patients who have a history of blood donation in their community, treatment is no different, since it is identical to a blood donation at your local blood bank. The only difference is that it is done more often (weekly) than voluntary blood donation (usually every 56 days) and therefore patients often report being fatigued and weak after numerous treatments, however, they are necessary to prevent damage to the patient or prevent additional damage to the patient, and to prevent death. If you are in "aggressive treatment" (at least weekly) you "may" experience varying degrees of tiredness and fatigue. For advanced patients undergoing vigorous weekly treatments for extended periods of time, some have reported that they have had to stop working or get assistance from family or friends with household chores and child care. Family members and friends should be informed that treatment is necessary to save the patient's life and understand that physical and emotional support are essential for the patient's successful completion of initial treatment. Other patients actually report feeling "invigorated" after each treatment with a few days of tiredness after each treatment and then back to normal. Be sure to discuss any side effects that you experience with your physician.
Q: Is hemochromatosis reversible through phlebotomy or must a patient undergo phlebotomy on a regular basis for the rest of his life? Does phlebotomy eventually ease the symptom so that this treatment may stop?
A: The symptoms of iron overload/hemochromatosis sometimes can be improved or even reversed (i.e., a woman infertile from hemochromatosis and told to adopt a child was diagnosed, treated and now has a biological child). Treatment, however, should continue, for the rest of the patient's life, usually at a rate of three or four phlebotomies per year, although this rate can differ slightly from patient to patient. Aggressive, weekly phlebotomy will eventually remove the stored iron in the body, however, the iron will once again accumulate if regular phlebotomy is not maintained for the rest of the patient's life. Remove that stored iron as safely and quickly as possible and keep it out with regular phlebotomy for the rest of your life! Remember, once you are "de-ironed", don't stop! Bloodletting is for life and if you don't regularly have blood removed, the iron will simply build up again and store in vital organs. Note: if iron overload is due to "acquired hemochromatosis" through iron pill ingestion for instance, then once deironed, the treatments can stop permanently.
Q: I have a fear of needles; isn't there any other way to be treated?
A: First of all, if you have a fear of needles, you are not alone. Phlebotomy (bloodletting) is the safest and most effective way to treat iron overload and prevent the damage and premature death of the patient. Phlebotomy is much more effective than drug treatment which is cumbersome and has side effects. Yes, there are needles, but there are some "tricks" that you can use. Some nurses use lidocaine on the arm (EMLA creme) before the procedure to make needle insertion more comfortable; some patients put hot compresses on the arm to help make it more "ready" for the treatment followed by a cold pack afterwards; others put vitamin E on the arm where the needle will go several hours before the procedure (do this to both arms since you don't know each time which arm will be used).
Getting a phlebotomist (nurse or person who does the bloodletting procedure) with whom you can work well and feel comfortable is very important, too. If you find such a person, request him/her each time, learn their schedule, and you will probably have a better experience with your treatment. If a nurse or technician makes you feel uncomfortable, physically or mentally, then get someone else if at all possible. You want to be relaxed for the procedure. There is also a "butterfly" needle which some patients have reported as much more comfortable than the regular needles used for blood donation. Ask questions and use these suggestions, it will make it much easier in the long run.
All in all, you will get "used" to the weekly bloodletting and find that usually it is just as simple as donating a unit of blood. And, remember, phlebotomies certainly are preferable to the alternative--organ damage and serious health conditions (which involve many needles), not to mention premature death, that would result from no treatment at all. Discuss your fears with your physician and the phlebotomist so that they can work with you to make this experience as comfortable and pleasant as possible. If your fear of needles and/or blood is extreme, some patients have been able to comply using sedatives and tranquilizers prior to the procedure. Remember, this procedure is identical to a blood donation, a common, everyday medical procedure performed by many community minded citizens around the country on their "lunch break". Most patients do not have any problems or unusual fears concerning this procedure, but if you do have a great fear, it is imperative that the medical team know about it so that you can work out a plan that will allow you to be treated. And, remember, you are not alone in your fear of needles, which is very common. Compliance with the treatment plan is essential for a good outcome. Many patients who have had a fear of needles, have overcome this fear and completed their treatments successfully and gone on to counsel other patients who feel as they used to about the treatment! Remember, if you DON'T get treated, you will have far more needles than you could imagine from the resulting illnesses such as diabetes, liver transplant, etc. The sooner you start treatment, the fewer phlebotomies you will need overall. The prescription should read: "Dx: Hemochromatosis--Phlebotomize patient as long as hct. is greater than 35%" This prescription should be good for one year and renewed annually.
Q: Is the blood I give during my treatment used as donor blood? The blood bank said they were going to discard it? Is there something wrong with my blood? I thought HH wasn't a "blood disease" or infectious?
A: Some blood banks do use the hemochromatosis blood as donor blood, but most blood banks in the U.S. do not. There is nothing wrong with hemochromatosis blood; HH is not a blood disease, nor is it infectious. HH blood can be used as donor blood as long as it meets the standards and tests of the blood bank (i.e. free from HIV, hepatitis, etc.). HH blood is not contagious or infectious in any way. The FDA was petitioned by the late Victor Herbert, MD JD, of Mt. Sinai School of Medicine in New York City, NY, to use hemochromatosis blood as donor blood. Although the FDA did not immediately change their policy, more petitions followed. In the past, the blood bank was using what many consider to be an "outdated" policy which says that any patient who gives blood for a "medical reason" is a "motivated donor" and they feel that motivated donors' blood is not as "safe" as other blood donations because donors might donate (in order to save their own lives due to the medical condition) when they personally know that they shouldn't (i.e. they have HIV, hepatitis, etc.). The blood bank feels that people who are "motivated donors" will not tell them about HH so that they can donate blood for free to avoid the cost of phlebotomies.
Leading doctors around the country have urged the AABB and the Red Cross to change their policies concerning HH patients, who are shown to be just as safe as the general public when donating blood. In 1999, the FDA approved the use of hemochromatosis blood as donor blood. Any blood bank can apply for a "variance" to use HH blood as donor blood. The FDA did not issue a mandate that all blood banks had to use HH blood as donor blood, but did give them the option to do so if they decided to do so. More than fifty blood banks around the USA accept and use HH blood as donor blood. If you want your local blood bank to use HH blood as donor blood, you can contact the blood bank director and discuss how their policy might be changed in the future. You can find a list of these blood banks on the AHS web site or the FDA web site (www.fda.org) . Of course, there are many patients who have hemochromatosis and know it and who donate blood without telling the blood bank. There are also many patients who have hemochromatosis and don't know it and are donating blood to the blood bank. Most blood banks do not test donors for iron overload or hemochromatosis. The American Hemochromatosis Society feels that HH patients are very "special" since they are "super donors".
Q: Is there a special diet I should eat or foods I should avoid?
A: Basically, iron in the diet is not going to make much difference in relation to your treatment, however, it is wise to check the labels of processed foods for their iron content. For instance, certain breakfast cereals contain 100% RDA of iron as do other products. Avoid alcohol and vitamin C which enhance iron absorption, cooking in cast iron cookware, and never take iron pills or supplements containing iron. Hemochromatosis patients should not eat raw seafood or shellfish (cooked is fine) due to a bacteria (vibrio vulnificus) which can kill the patient within hours of ingestion (due to a compromised liver which many HH patients have) unless emergency treatment of antibiotics (tetracycline) is administered. (Note: this can also happen to fishmen who handle and clean fish). Drink tea and coffee with your meals which will help block the iron in the foods you do eat. For more details on diet, you can purchase "The Hemochromatosis Cookbook" by Cheryl Garrison available through any major book store, amazon.com, or the Iron Disorders Institute (IDI).
Q: Is iron overload/hereditary hemochromatosis "curable"?
A: Iron Overload is not curable if it is genetic hemochromatosis, hereditary hemochromatosis (HH). The patient will need to be monitored and treated for the rest of his/her life. However, iron overload is curable in the case of acquired hemochromatosis such as massive doses of iron pills, etc. Once the patient is "de-ironed", he/she will not need to be treated anymore. For HH, we hope that research in the future will find a cure for this condition, until then, treatment and early diagnosis, offer the next best thing to a cure. In fact, HH can be prevented with early genetic screening and detection of the high risk gene mutations. In such cases, patients can be genetically screened, identified, and monitored, so that they will never have high iron at any time in their lives, thusly preventing organ damage and premature death. Of course, someday, we hope that there will be a complete cure for hereditary hemochromatosis.
Q: If hemochromatosis is a genetic disease, should other family members be tested? Which ones and when?
A: ALL blood relatives (not just the immediate family) of the iron-overloaded individual should be strongly warned to be screened immediately with the iron profile of serum iron, TIBC, and serum ferritin) and the new DNA genetic test. All should be monitored annually for the rest of their lives. This includes men, women (pre and post menopausal) and minor children. If the HH patient has children, the spouse should also be tested. Actually, everyone in our society should be tested, but especially family members. Due to the lack of public awareness and physician education about hemochromatosis, most family members are not screened and many diagnoses are missed as a result.
Q: I told my family members that I had hereditary hemochromatosis and what tests to have done, but they won't listen to me; they say that their own doctors tell them "not to worry". I am worried; what can I do?
A: Family compliance with screening is often very challenging to the first member of the family to be tested. Try to find several members who are willing to have the DNA test at least. If those tests are confirmed, often other members will take new "interest" and comply when they see the DNA test results in black and white. Another possible tactic is to have your doctor contact your family members' doctors, either by telephone and/or letter and urge their doctors to screen them with the proper blood tests and DNA tests. Another possible tactic is to obtain DNA test kits from a lab and mail them to family members or bring the kits to a family reunion, wedding, holiday gathering, and distribute them at that time and explain the importance of the test. Finally, if the family members have children, urge them to have the DNA testing if not for themselves, to do it for the sake of their children. People often will be tested when their children's and grandchildren's health is at stake. Home testing is also another way to encourage family members to be tested. By genetically testing family members at home, and avoiding the medical setting of the doctor's office, many family members will be tested. We recommend HealthCheckUSA (www.healthcheckusa.com) for genetic testing. It is fast, simple, and painless. A DNA test kit can be mailed directly to your home and is suitable for adults, children, and infants.
Q: My pediatrician says I don't need to worry about my children between the ages of 2 years and 18 years old having iron overload. He says it's an "adult onset" disease; is this true?
A: No! Pediatric hemochromatosis is very real and more and more cases are being identified every day. Sandra Thomas, President of the American Hemochromatosis Society, has founded the "Children HHelping Children" Screening & Awareness Project to screen, diagnose, and treat children under the age of 18 years with iron overload/hereditary hemochromatosis. All children should have the DNA test ideally at birth to ascertain their possible risk for HH and also have the TS and serum ferritin tests after the age of two years to see if they are clinically iron overloaded at that current time. If necessary, phlebotomy treatment should be started in the child if he/she is loading too much iron, but you should make sure you are using a doctor who is familiar with pediatric hemochromatosis. Children with iron overload often have cardiac symptoms as well as liver disease. They have high saturations and fairly normal serum ferritin readings. More research is needed to establish standardized protocols for pediatric hemochromatosis, but it is imperative that you know your child's genetic risks for HH to make sure that your child can have a normal life expectancy through preventive measures. Some of these cases may be "juvenile hemochromatosis". Only an expert in hemochromatosis will be able to truly identify the children at risk and those who have developed the disease during childhood. Liver biopsies are not recommended for children unless evident liver disease is present. A non invasive test with a ferritometer can measure the amount of iron in the liver if this measurement is needed.
Q: If I have the double gene mutation (homozygous) for hemochromatosis but am not clinically iron overloaded (have high iron levels on lab results) at this time, can I develop iron overload later, such as in 2, 5, or 10 or more years later?
A: Yes, patients with the double gene may develop iron overload at some later time in their lives, therefore, they should be annually monitored by their physician for transferrin saturation and serum ferritin. It is important to note that anyone can develop clinical iron overload, whether they have one, two, or no mutations for HH.
Q: If I have the single gene mutation (heterozygote) and am a "silent carrier" for hemochromatosis, will I become iron overloaded?
A: Most carriers do not become ill (have symptoms or elevated iron levels) during their lifetime, however, they should avoid the same things that the double gene person does. Carriers are at higher risk than non-carriers for loading excess iron and can become iron overloaded so they should be annually monitored by their physicians. Carriers of the single mutation, known as "silent carriers" should also refrain from heavy alcohol consumption and/or massive vitamin C supplementation (you may drink orange juice but do not take mega doses of vitamin C pills), and vitamins containing iron. Single gene carriers are at risk of loading high iron and should annually monitor their iron levels with serum iron, TIBC, and serum ferritin tests.
Q: No one in my family has ever been diagnosed with hemochromatosis or had any of the symptoms; how could I possibly have this disease?
A: Many patients who have full blown hemochromatosis (the double gene mutation/homozygote) have family members who have it also but do not know it or who have died from hemochromatosis but it was never diagnosed as iron overload. Also, it is possible that all of the family members in the family (living or deceased) have also been asymptomatic single gene mutation "silent carriers", lived to old age and no one had the double gene until you, the double mutation patient, were born and your diagnosis of the double gene mutation was discovered. Therefore, those people who say they are the "only" member of the family are incorrect. There are definitely carriers in the family, all double gene patients' mothers and fathers MUST have been at least single gene/heterozygote carriers, and either or both parents could be double gene/homozygotes as well. Many patients ask if they got HH from their mother's or father's side of the family. The answer is that they got it from BOTH sides of the family; HH is an autosomal recessive mutation, therefore, you must inherit one mutated gene from your mother and one from your father, for you to have the double mutation. Many families are startled to learn after an initial diagnosis in that family, that many other family members also have HH! If both parents are double gene, then all of their children will also have the double gene.
Q: I had the DNA test and found out that I have the double gene mutation. My husband, who has always been in good health, was tested and we were shocked to learn that he is a "silent carrier" of the single HH gene. We know now that our four children have inherited various combinations of our HH genes from us; two now have been diagnosed with hemochromatosis and two are also silent carriers. Now all of our young grandchildren are being DNA tested by their pediatricians. We feel very guilty about passing these genes on to our children and grandchildren...do others feel this way, too?
A: As we proceed into an era of genetic testing, it is important to remember that NO ONE is free of genetic defects. In fact, we can estimate at this time that everyone has at least three or four genetic defects which may or may not manifest during our lifetimes. As genetic testing becomes more "mainstream" more and more people, like you, will learn what their genetic status is for various genetic diseases. When you consider that people for many generations have died of diabetes, cancer, etc., we can assume that many of these cases were actually due to a gene carried in the family or a "genetic predisposition" for a particular disease that has been passed from generation to generation. Genetic testing is no longer in the realm of "science fiction" and is quickly becoming a powerful tool for doctors to monitor patients and provide therapies which may delay, or even prevent, as in the case of HH, lethal symptoms of a disease. The good news is that hereditary hemochromatosis is a genetic disease whose symptoms, organ damage, and premature death can be completely prevented! Therefore screening and early diagnosis are the keys to full life expectancy! You have nothing about which to feel guilt; you are getting your family members screened; and, if appropriate, into treatment. By becoming educated about hereditary hemochromatosis, you are saving lives--now and for generations to come!
Q: My family and friends have never heard of hereditary hemochromatosis and my doctor admits he knows little about it. Why doesn't anyone know anything about HH if it is so common? I feel all alone.
A: Although it is the most common genetic disease in the U.S.A., because there is no routine screening for HH at this time, most cases go undiagnosed. HH is all around you--your families and your friends--they just don't know it. You can help increase awareness in your family, in your community and save lives yourself. You can encourage your doctor to attend read the AHS web page and to attend HH symposiums and CME seminars held around the country. You are not alone; there are thousands of HH patients all over the country who feel as you do. If you have a computer, you can link up with other HH patients via the Internet or the online discussion group, "Families HHelping Families" on the AHS web site.
Q: What is the American Hemochromatosis Society (AHS) and what is its mission?
A: The American Hemochromatosis Society (AHS) is the leading non profit organization for information on genetic testing for iron overload/hereditary hemochromatosis, and information and support for pediatric hereditary hemochromatosis. AHS was founded on March 30, 1998 by Sandra Thomas, a carrier of the HH mutation and whose mother, Josephine Bogie Thomas, was a victim of HH and was diagnosed in 1983 and died from complications of the disease on May 13, 1999. AHS originally was based in Delray Beach, Florida, and is now based in Lake Mary, near Orlando, Florida. It is a 501(c)3 non-profit organization whose mission is to ban genetic discrimination, promote genetic testing for HH of the American population, and emphasize a focus on pediatric hereditary hemochromatosis and neonatal hemochromatosis. More than 1.5 million Americans who have iron overload/hereditary hemochromatosis and another 32 million Americans who are "silent carriers" of the single mutation, will need to be served with information and support...AHS will be there for them. AHS serves both physicians and patients.
Q: Are there any books about iron overload that AHS offers?
A: Yes! A list of books on HH by various authors appears on the AHS web page and AHS president, Sandra Thomas, is currently writing a book about hereditary hemochromatosis. An educational slide presentation and video are in production. AHS also has free educational materials which can be mailed to patients and their families. Please send a self addressed business envelope with two stamps.
Q: How can I get more information from the American Hemochromatosis Society (AHS) on iron overload/hemochromatosis by email and the Internet?
A: You can email Sandra Thomas, President, American Hemochromatosis Society, at: mail@americanhs.org The web page address is: www.americanhs.org AHS has it's own discussion group called, "Families HHelping Families". See the web site for more information on how to join this group.
Q: How can I get more information from AHS on iron overload/hemochromatosis by mail? How can I make a donation to AHS?
A: For free information by mail write to the AHS directly (Please, enclose a self-addressed envelope with two stamps):
American Hemochromatosis Society, Inc. (AHS) (non-profit)
Sandra Thomas, President/Founder,
4044 W. Lake Mary Blvd., #104, PMB 416,
Lake Mary, Florida 32746-2012 USA
Telephone: 407-829-4488
Toll-free Info Line: 1-888-655-IRON (4766)
(Due to the volume of mail, please allow four to six weeks for delivery)
If you would like to make a memorial donation or a donation in someone's honor, please indicate that information with your donation. AHS is a 501c3 non profit organization and all donations are gratefully received. Please make your check payable to: AHS.
http://www.americanhs.org/faq.htm
http://www.americanhs.org/testing.htm
Warning: The doctors on the Board of Directors of The American Hemochromatosis Society state that transferrin saturation percentage greater than 40% and serum ferritin greater than 150ng/mL could indicate clinical iron overload/iron storage in the body and treatment with phlebotomy (bloodletting) should be considered regardless of DNA test results. This means that patients' treatment should not be based on genetic test results alone whether positive or negative. The DNA test is a powerful tool to help us find people at risk; 85-98% of patients with clinical iron overload have the hemochromatosis mutations, however, the most important point to remember is that excess iron needs to be evaluated and treated. William Crosby, MD, (see photo above) the late well known hemochromatosis physician and researcher, declared that if a patient has demonstrated excess iron then they are in danger of organ damage and premature death. Patients should be aggressively (usual rate is weekly or twice weekly depending on the stage of the disease) treated with phlebotomy (bloodletting identical to blood donation) for excess iron! Treatment frequency can be adjusted for individual patients with special circumstances (elderly, other medical problems, etc.)
Do you or anyone in your family (living/deceased) have (or have a family history of) these symptoms or risk factors?
Arthritis
Joint pain/Replacement
Diagnosis of Fibromyalgia/Chronic Fatigue Syndrome (CFS)
Anemia
Hypothyroidism (low thyroid function)
Impotence/ED/Early menopause / Irregular periods
Infertility /hysterectomy/have never had children
Diabetes mellitus /High blood sugar
Darkening or "tanning" of the skin without exposure to the sun
Heart Disease/Heart Attack
Stroke
Irregular heartbeat
Bypass surgery
Hair loss/Hair thinning
Weight loss
Set off airport metal detectors for no apparent reason
Ancestry of Celtic (Irish/Scottish/Welsh) British/Northern European origin
Liver disease/hepatitis/cirrhosis/primary liver cancer/elevated liver enzymes
Enlarged liver/yellow skin & yellow eyes (jaundice)
Dark urine
Red palms of the hands/Abdominal pain
Liver and/or heart transplant.
Warning: The doctors on the Board of Directors of The American Hemochromatosis Society state that transferrin saturation percentage greater than 40% and serum ferritin greater than 150ng/mL could indicate clinical iron overload/iron storage in the body and treatment with phlebotomy (bloodletting) should be considered regardless of DNA test results. This means that patients' treatment should not be based on genetic test results alone whether positive or negative. The DNA test is a powerful tool to help us find people at risk; 85-98% of patients with clinical iron overload have the hemochromatosis mutations, however, the most important point to remember is that excess iron needs to be evaluated and treated. William Crosby, MD, (see photo above) the late well known hemochromatosis physician and researcher, declared that if a patient has demonstrated excess iron then they are in danger of organ damage and premature death. Patients should be aggressively (usual rate is weekly or twice weekly depending on the stage of the disease) treated with phlebotomy (bloodletting identical to blood donation) for excess iron! Treatment frequency can be adjusted for individual patients with special circumstances (elderly, other medical problems, etc.)
Do you or anyone in your family (living/deceased) have (or have a family history of) these symptoms or risk factors?
Arthritis
Joint pain/Replacement
Diagnosis of Fibromyalgia/Chronic Fatigue Syndrome (CFS)
Anemia
Hypothyroidism (low thyroid function)
Impotence/ED/Early menopause / Irregular periods
Infertility /hysterectomy/have never had children
Diabetes mellitus /High blood sugar
Darkening or "tanning" of the skin without exposure to the sun
Heart Disease/Heart Attack
Stroke
Irregular heartbeat
Bypass surgery
Hair loss/Hair thinning
Weight loss
Set off airport metal detectors for no apparent reason
Ancestry of Celtic (Irish/Scottish/Welsh) British/Northern European origin
Liver disease/hepatitis/cirrhosis/primary liver cancer/elevated liver enzymes
Enlarged liver/yellow skin & yellow eyes (jaundice)
Dark urine
Red palms of the hands/Abdominal pain
Liver and/or heart transplant.
Mrs. Peel said:
Me too. Well, I drink the black tea all day until 5 pm. I think that it's just a case of slow creep. What is interesting is that they say that iron can be elevated in concert with inflammation and when you take the iron down, the inflammation goes down too. With my levels, I'll probably have to do 30 "decantings". I just want it down. Like now.
I got my ferritin levels before the blood donation. It is 282 and result sheet says 30-400 as normal range.That is not normal based on the above research. I am also doing dna test and see what comes out and avoiding LPC for now. Though I occasionally drink tea that little caffine with lunch, I will have to make it regular and see how it helps chronic anxiety and hyper sensitivity to stress I am suffering from.
Thank you for the information. I've never had my ferritin levels checked and am staring at a blood order work form which has not been attended to yet. Just checking, it does not even appear that this test is listed in print, yet the physician (who knows I smoke 
) wrote ferritin, TSH (hyperthyroid) and other things not mentioned in the above post, so will call before doing this blood work to ensure the proper things are measured.
) wrote ferritin, TSH (hyperthyroid) and other things not mentioned in the above post, so will call before doing this blood work to ensure the proper things are measured.
I got my tests back. My ferritin is at 44.8, and my iron at 139. So, I guess it's pretty ok for now. My father had the genetic test done, and he definitely has hemochromatosis (heterozygote). So, I'll keep checking my levels, just in case. I'm still going to do a course of DMSA, probably, to lower the iron a bit, and have the transferrin tested. These doctors don't prescribe a blood test to check the three parameters, unless you know what you are doing and ask specifically. So, for those wanting the test done, make sure you ask for serrum iron, ferritin and transferrin to be tested at once.
Nancy2feathers
The Living Force
My Ferritin level came back 98. Reference range by the chart I have is 11-264. So at 98 is decanting recommended? Iron=114, dTIBC=259, %SAT=44.
From: http://www.irondisorders.org/phlebotomy
Iron is removed therapeutically from the body in two ways, by blood donation (phlebotomy) or chelation therapy (pharmacological removal). The therapeutic approach used, the amount of iron removed, follow-up testing of iron levels, dietary and behavioral changes made will all differ according to the patient’s iron levels, general health, age and ability to tolerate the chosen approach.
Phlebotomy definition:
A phlebotomy is blood removal; when used as a treatment, it is called therapeutic phlebotomy (TP). The procedure is identical to blood donation, except that TP requires a doctor’s prescription.
Physicians prescribe therapeutic phlebotomies for patients who have too much iron stored in their bodies and whose hemoglobin levels are sufficient to tolerate blood removal.
Each blood donation, or phlebotomy treatment, removes about 500cc of blood and reduces the amount of iron in the body by about 250 milligrams.
Phlebotomy Phases of Therapy: induction, transition, and maintenance
Induction is when therapy is initiated. Transition is the phase in which iron reduction is taking place to return iron levels to a normal healthy range. Once iron levels reach satisfactory and healthy levels, a patient enters the maintenance phase.
Induction:
Key to successful iron reduction without generating symptoms or accelerating disease depends on several important factors. The single most important factor is how the doctor writes the order for phlebotomy. Besides this critical first step other important factors are patient compliance with scheduled phlebotomies, diet and behavior modifications and continued education.
With few exceptions Iron Disorders Institute Advisory Board recommends a pre-treatment hemoglobin of 12.5g/dL. Exceptions will include some females or patients with liver or blood diseases.
For most hemochromatosis patients, an order might be written as follows: "Phlebotomize 500 cc once a week** if Hgb=or >12.5g/dL" (38% hematocrit)
**period of time should reflect frequency desired.
Transition:
During this phase iron levels may be erratic or fall predictably. The frequency of phlebotomies may change from twice weekly, to weekly or monthly. Generally when a patient’s serum ferritin is less than 500ng/mL, the frequency of phlebotomy can be slowed to once a month. Each person is different and responds to treatment in a unique way. Much depends on age, the extent of iron saturation, serum ferritin levels, hemoglobin response, one's physical condition including symptoms, and the speed with which an individual unloads iron. Also, compliance with therapy schedules and care with diet will impact this phase tremendously.
The goal of the transition period is the safely usher the patient from therapeutic phase into the maintenance phase. During this period, if iron levels are allowed to fall steadily, over time and not too rapidly, the body can reach healthy iron levels and possibly without competition from the genes that are programmed to load iron.
Maintenance:
Maintenance patients are those who have reached healthy iron ranges and who can remain within those healthy ranges by donating blood periodically.
A healthy range for ferritin is 25-150ng/mL. But patients in therapy for iron reduction should achieve a serum ferritin below 50ng/mL on at least one occasion. Thereafter, the ferritin can be maintained within the range of 25-75ng/mL.
The patient may donate blood routinely as defined by attending physician for optimum quality of health or may have periodic therapeutic phlebotomy by doctor's order. Frequency of donation or therapeutic phlebotomy will depend upon patient's Personal Health Profile as observed by patient and attending physician: age, weight, response to treatment, symptoms, rate of iron unloading and general physical condition. At anytime during treatment you experience symptoms of heart irregularities or severe abdominal pain or symptoms of anemia, alert your physician immediately.
Symptoms of anemia can often be mistaken by a patient as symptoms of iron overload. Symptoms of anemia or iron overload can include: fatigue, heart arrhythmia, headache, sensitivity to cold, shortness of breath, dizziness and restless legs syndrome. Lab tests are needed to distinguish between the two.
If excess iron has had enough time to damage critical organs, one may never restore these damaged organs to full function. Medications may be required to address these symptoms or disease that has developed.
During the maintenance phase, and so long as a patient remains symptom-free, the doctor will re-test iron levels about every 3 months. The initial three-month exam upon reaching healthy iron levels will provide a baseline or the first set of numbers after a series of phlebotomies whereby a person's pattern of un-loading can be established. These numbers are very important to the management of iron balance.
The amount of time required to reach the maintenance phase of treatment will vary. Thereafter, how often that person must have a phlebotomy to keep iron levels in a normal range will depend on compliance. Many hemochromatosis patients abandon therapy once they achieve normal iron levels. This sets them up for irreversible organ damage and the need for repeat series of therapeutic phlebotomies.
For the hemochromatosis patient maintaining iron balance is a life-long effort—timely blood donation is their “drug”.
Serum Ferritin and Phlebotomy Frequency:
In most cases the serum ferritin will drop by about 30ng/mL with each full unit of blood removed. This helps the physician to form an estimate of when the serum ferritin is will be below 1,000ng/mL.
For patients whose initial serum ferritin (SF) is greater than 1,000 ng/mL, phlebotomies can be as frequent as twice a week. The SF should be evaluated every 4-6 weeks until it is lowered below 750 ng/mL. SF above 750 but below 1,000 is still a very high and may require continued weekly phlebotomies. However, issues such as inflammation and alcohol consumption should be taken into consideration when maintaining weekly or adjusting the frequency of blood removal. A patient may need to continue on aggressive removal (at least once a week) if iron levels are dropping at a fairly steady pace. When serum ferritin falls dramatically, highly suspect are inflammation or other factors that influence serum ferritin levels.
Ferritin drops by about 30-50ng/mL with each full unit of blood removed. Ferritin levels can be distorted. Individuals who have liver damage such as cirrhosis will unload iron faster than those without liver damage. Other factors that may skew ferritin include presence of inflammation or infection and alcohol or nicotine consumption (gums, patches, chews). Checking ferritin periodically can protect against undue iron deficiency anemia caused by overbleeding.
Patients undergoing de-ironing are at risk for overbleeding that can take place in the latter part of de-ironing. Bleeding a patient until the hemoglobin is below normal and the patient has mild iron deficiency anemia is no longer the best practice. There is no known benefit to the forced-sustained anemia, a practice that was established nearly three decades ago. Iron Disorders Institute Advisory Board recommends against phlebotomy (with few exceptions) for patients whose hemoglobin is lower than 12.5g/dL.
Prior to treatment, a patient will have a serum ferritin greater than 200ng/mL (females) or 300ng/mL (males) with an accompanying transferrin-iron saturation percentage greater than 45%.
When ferritin is above 1000ng/mL phlebotomy treatments will be aggressive usually as frequent as twice weekly while tolerable and until ferritin drops below 1000ng/mL.
Once serum ferritin is below 500ng/mL, the frequency of treatment may slow down from twice weekly to once a week or even to every other week depending upon the patient's condition, behavior (eating habits) and ability to unload iron.
During de-ironing: blood contains water and other nutrients. Adequate fluid intake guards against dehydration. Patients are encouraged to take a once-a-day multi-vitamin without iron to support the loss of nutrients. Look for vitamins with minerals (except iron) and B complex.
Otherwise, serum ferritin can be checked periodically such as every 3-6 months to determine the patient's unloading pattern.
Most blood donation centers allow one donation every eight weeks. If you are a candidate for maintenance, then a periodic blood donation will suffice. If you are found to need treatment, needing more than one extraction in eight weeks, the attending physician will provide you with the necessary order for additional phlebotomies. Your gastroenterologist or hematologist may refer you back to your family physician for the maintenance phase of your therapy. Afterwards, you may resume a normal, happy healthy life with only a small adjustment to your schedule: a life-saving, blood donation every 8 to 10 weeks.
My Iron Levels
Body iron levels are determined by measuring serum ferritin, fasting serum iron and total iron binding capacity (TIBC). A patient’s transferrin saturation percentage (TS%), an important measure of the body’s capability to bind, transport and maintain safe levels of iron. TS% is calculated by dividing serum iron by TIBC multiplied by 100%. TS% is normally about 35-40%.
Serum ferritin is a measure of stored or contained iron. SF varies by age and gender.
With the exception of infants and newborns, iron overload is suspect when both serum ferritin and TS% are elevated. There are other conditions of high body iron where only the serum ferritin is elevated. These individuals can benefit from periodic blood donation as elevated serum ferritin is a possible early warning that disease is forming.
Hemoglobin indicates the amount of functional iron, that is, the iron that is carrying oxygen to tissues so that organs can function.
What is the role of hemoglobin in phlebotomy?
Hemoglobin value will determine if a person can tolerate phlebotomy to reduce iron levels. If the hemoglobin value is too low, but iron overload is present, iron chelation therapy is used to reduce excessively high iron levels.
For most hemochromatosis patients the hemoglobin levels will rebound and remain in a normal healthy range following phlebotomies or blood donation. Patients with significant iron overload can tolerate frequent treatments because their hemoglobin will rebound very quickly. As the body manufactures new blood to replace that removed, the new liquid acts like a sponge; it draws the iron out of the body tissue (stored in ferritin) to synthesize hemoglobin in the new blood. Once iron becomes part of hemoglobin it can be safely removed with the next treatment.
Hemoglobin levels prior to blood donation should be 12.5g/dL with few exceptions.
Why do I need a phlebotomy?
Phlebotomy reduces excessive and life-threatening levels of body iron. Some patients diagnosed with hemochromatosis have already built up 5 or 10 grams (or more) of excess iron in their bodies. These patients will require aggressive treatment and sometimes will be phlebotomized (or give blood) as often as once or twice a week. For individuals whose iron levels are only modestly elevated, blood can be simply donated every eight weeks without a prescription.
If serum ferritin is less than 1,000ng/mL at the time of diagnosis, the chances of liver cancer is less than 1%. But if diagnosis occurs after serum ferritin has risen above the 1,000 mark, the risk of liver cancer jumps 20-200 fold depending on the individual.
Pretreatment Lab work:
Before the phlebotomy may be done, hemoglobin or hematocrit must be checked. Usually centers have labs on site where the results are forwarded to the attending nurse or phlebotomist. With few exceptions, if the hemoglobin is too low (below 12.5g/dL) the phlebotomy should be postponed to avoid the risk of over-bleeding and unnecessary iron deficiency. Otherwise a person can become iron avid and set themselves up for increased symptoms and struggles to achieve iron balance.
Keep good records:
You may request a copy of lab work from the office manager in charge of records in the doctor's office. Obtaining lab results is highly recommended so that a journal may be compiled. Journals will become a valuable tool if you have to move to another town or seek treatment from another doctor. Knowing about your disorder and understanding the diagnostic process helps to speed recovery and avoid future health setbacks. Iron Disorders Institute provides a free copy of its Personal Health Profile in the Resource Center of the website. These forms are designed to help patients track important information that can be shared with the healthcare provider.
Where are phlebotomy treatments performed?
Phlebotomies might be performed at a blood donation center, as an outpatient in a hospital or even in a doctor's office. Your doctor will probably advise places that provide the treatment. Consider convenience of location, cost to do the phlebotomy, and how responsive the center is to your situation.
In 1999 the FDA declared hemochromatosis blood to be safe for transfusion (to give to others) so long as the hemochromatosis patient qualifies to donate blood as volunteer donors. As a result, many private blood centers and one American Red Cross center offer hemochromatosis donor programs.
The Therapeutic Phlebotomy (TP) Procedure Described:
The process varies slightly depending on the treatment site; following is a general step by step of what takes place.
After the preliminary tests for hemoglobin and hematocrit are finished, a phlebotomist prepares you for the procedure. The phlebotomist can sometimes be a nurse or doctor, but regardless, this individual is trained to perform needle sticks.
If your hemoglobin-hematocrit are sufficient and in accordance with the doctor’s order, you will be prepared for blood removal. Usually you will stretch out on a comfortable recliner chair. The attendant takes your blood pressure, temperature and heart rate (pulse). These numbers will be recorded on your medical chart for future reference.
An elastic band is tied around the upper part of the arm. This helps the vein to stand up. You may have to squeeze a soft rubber ball or make a fist several times to help the vein remain accessible. The nurse then swabs an iodine-based antiseptic on the vein and all around the area near the vein. This is to disinfect the area where the needle is to be inserted and to make certain no bacteria gets into your system during treatment.
A special needle is then inserted into the vein. You might feel a little pinch, but it lasts only a second. A piece of tape is placed over the needle to keep it stable; you just sit back and relax. The needle used is large enough for blood to flow quickly without clotting. Some patients have a fear of needles or vein access difficulties. There are ways to address these issues but they are not routine and require assistance from the healthcare provider and in some cases involve a surgeon. See Phlebotomy Problems and Issues
While the blood flows, some like to bring a headset with earphones or a good book to read during treatment. While relaxing, the blood flows from the needle, into a tube, and then into the blood bag. The blood bag sits onto a scale that measures the weight of the blood. When 500cc (about one-half pint) of blood is removed the donation or phlebotomy is complete. Some blood centers can offer Double Red Cell Apheresis (DRCA) treatment to hemochromatosis patients. DRCA removes more red blood cells but the amount is less than double.
About 250 mgs of iron are removed with each unit of blood removed. The procedure will take as few as ten minutes or as many as thirty; again, it depends on how hydrated you are, your vein access and the thickness of your blood.
After the Treatment:
After the phlebotomy, the nurse will remove the needle from your arm. You may need to keep the area bandaged or you may need to apply mild pressure if bleeding continues. You should rest for about 20 minutes following therapy. This is a precaution to insure you do not get weak or dizzy. You may be given a snack while you are resting and it is suggested you eat something after your therapy.
Your blood will be discarded unless you are enrolled in one the blood centers with an FDA variance to use hemochromatosis blood for transfusion. You can find a list of these centers on our website in the Resource Center.
Between phlebotomies:
To prepare yourself, be sure that you are getting adequate fluids. A daily multi-vitamin without iron is recommended because with treatment iron is removed but so are other nutrients. Nothing replaces a diet with variety but a daily multi can offer benefit during the phlebotomy phase. Be careful about water consumption. Gulping great amounts of water prior to therapy is not wise; you may actually cause yourself to become water intoxicated, a serious condition that can result in death. Hydrate yourself slowly over days; do not wait until the last moment.
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Problems and Issues:
Fear of needles is a powerful deterrent to iron reduction. It is a common complaint expressed by men and women alike. There are not too many alternatives for such a patient, but there are some steps that can help. Taking a light sedative (prescribed by the doctor) can relax a person sufficiently to insert the needle. Having a support person present to distract a nervous patient can be helpful. Listening to music through a headset can also be distracting. Double Red Cell Apheresis (DRCA) is a good choice for many of these patients. One stick allows nearly double the iron extraction saving the person from the anguish or anxiety of twice a week punctures.
Numbing agents such as Emla Cream can help in some cases. These creams temporarily numb the skin allowing the needle to be inserted. Check with your doctor about a prescription but first see if the blood center has any objections to the use of such a product.
Vein access is another issue. When patients require multiple and numerous blood extractions sometimes a chest port is an option to consider. Otherwise, veins in the legs can be used to remove blood.
Since scar tissue can build up significantly over time, a person whose arms are scarred might consider wearing a medical ID bracelet. This can distinguish them from individuals who may be chronic drug abusers.
Iron is removed therapeutically from the body in two ways, by blood donation (phlebotomy) or chelation therapy (pharmacological removal). The therapeutic approach used, the amount of iron removed, follow-up testing of iron levels, dietary and behavioral changes made will all differ according to the patient’s iron levels, general health, age and ability to tolerate the chosen approach.
Phlebotomy definition:
A phlebotomy is blood removal; when used as a treatment, it is called therapeutic phlebotomy (TP). The procedure is identical to blood donation, except that TP requires a doctor’s prescription.
Physicians prescribe therapeutic phlebotomies for patients who have too much iron stored in their bodies and whose hemoglobin levels are sufficient to tolerate blood removal.
Each blood donation, or phlebotomy treatment, removes about 500cc of blood and reduces the amount of iron in the body by about 250 milligrams.
Phlebotomy Phases of Therapy: induction, transition, and maintenance
Induction is when therapy is initiated. Transition is the phase in which iron reduction is taking place to return iron levels to a normal healthy range. Once iron levels reach satisfactory and healthy levels, a patient enters the maintenance phase.
Induction:
Key to successful iron reduction without generating symptoms or accelerating disease depends on several important factors. The single most important factor is how the doctor writes the order for phlebotomy. Besides this critical first step other important factors are patient compliance with scheduled phlebotomies, diet and behavior modifications and continued education.
With few exceptions Iron Disorders Institute Advisory Board recommends a pre-treatment hemoglobin of 12.5g/dL. Exceptions will include some females or patients with liver or blood diseases.
For most hemochromatosis patients, an order might be written as follows: "Phlebotomize 500 cc once a week** if Hgb=or >12.5g/dL" (38% hematocrit)
**period of time should reflect frequency desired.
Transition:
During this phase iron levels may be erratic or fall predictably. The frequency of phlebotomies may change from twice weekly, to weekly or monthly. Generally when a patient’s serum ferritin is less than 500ng/mL, the frequency of phlebotomy can be slowed to once a month. Each person is different and responds to treatment in a unique way. Much depends on age, the extent of iron saturation, serum ferritin levels, hemoglobin response, one's physical condition including symptoms, and the speed with which an individual unloads iron. Also, compliance with therapy schedules and care with diet will impact this phase tremendously.
The goal of the transition period is the safely usher the patient from therapeutic phase into the maintenance phase. During this period, if iron levels are allowed to fall steadily, over time and not too rapidly, the body can reach healthy iron levels and possibly without competition from the genes that are programmed to load iron.
Maintenance:
Maintenance patients are those who have reached healthy iron ranges and who can remain within those healthy ranges by donating blood periodically.
A healthy range for ferritin is 25-150ng/mL. But patients in therapy for iron reduction should achieve a serum ferritin below 50ng/mL on at least one occasion. Thereafter, the ferritin can be maintained within the range of 25-75ng/mL.
The patient may donate blood routinely as defined by attending physician for optimum quality of health or may have periodic therapeutic phlebotomy by doctor's order. Frequency of donation or therapeutic phlebotomy will depend upon patient's Personal Health Profile as observed by patient and attending physician: age, weight, response to treatment, symptoms, rate of iron unloading and general physical condition. At anytime during treatment you experience symptoms of heart irregularities or severe abdominal pain or symptoms of anemia, alert your physician immediately.
Symptoms of anemia can often be mistaken by a patient as symptoms of iron overload. Symptoms of anemia or iron overload can include: fatigue, heart arrhythmia, headache, sensitivity to cold, shortness of breath, dizziness and restless legs syndrome. Lab tests are needed to distinguish between the two.
If excess iron has had enough time to damage critical organs, one may never restore these damaged organs to full function. Medications may be required to address these symptoms or disease that has developed.
During the maintenance phase, and so long as a patient remains symptom-free, the doctor will re-test iron levels about every 3 months. The initial three-month exam upon reaching healthy iron levels will provide a baseline or the first set of numbers after a series of phlebotomies whereby a person's pattern of un-loading can be established. These numbers are very important to the management of iron balance.
The amount of time required to reach the maintenance phase of treatment will vary. Thereafter, how often that person must have a phlebotomy to keep iron levels in a normal range will depend on compliance. Many hemochromatosis patients abandon therapy once they achieve normal iron levels. This sets them up for irreversible organ damage and the need for repeat series of therapeutic phlebotomies.
For the hemochromatosis patient maintaining iron balance is a life-long effort—timely blood donation is their “drug”.
Serum Ferritin and Phlebotomy Frequency:
In most cases the serum ferritin will drop by about 30ng/mL with each full unit of blood removed. This helps the physician to form an estimate of when the serum ferritin is will be below 1,000ng/mL.
For patients whose initial serum ferritin (SF) is greater than 1,000 ng/mL, phlebotomies can be as frequent as twice a week. The SF should be evaluated every 4-6 weeks until it is lowered below 750 ng/mL. SF above 750 but below 1,000 is still a very high and may require continued weekly phlebotomies. However, issues such as inflammation and alcohol consumption should be taken into consideration when maintaining weekly or adjusting the frequency of blood removal. A patient may need to continue on aggressive removal (at least once a week) if iron levels are dropping at a fairly steady pace. When serum ferritin falls dramatically, highly suspect are inflammation or other factors that influence serum ferritin levels.
Ferritin drops by about 30-50ng/mL with each full unit of blood removed. Ferritin levels can be distorted. Individuals who have liver damage such as cirrhosis will unload iron faster than those without liver damage. Other factors that may skew ferritin include presence of inflammation or infection and alcohol or nicotine consumption (gums, patches, chews). Checking ferritin periodically can protect against undue iron deficiency anemia caused by overbleeding.
Patients undergoing de-ironing are at risk for overbleeding that can take place in the latter part of de-ironing. Bleeding a patient until the hemoglobin is below normal and the patient has mild iron deficiency anemia is no longer the best practice. There is no known benefit to the forced-sustained anemia, a practice that was established nearly three decades ago. Iron Disorders Institute Advisory Board recommends against phlebotomy (with few exceptions) for patients whose hemoglobin is lower than 12.5g/dL.
Prior to treatment, a patient will have a serum ferritin greater than 200ng/mL (females) or 300ng/mL (males) with an accompanying transferrin-iron saturation percentage greater than 45%.
When ferritin is above 1000ng/mL phlebotomy treatments will be aggressive usually as frequent as twice weekly while tolerable and until ferritin drops below 1000ng/mL.
Once serum ferritin is below 500ng/mL, the frequency of treatment may slow down from twice weekly to once a week or even to every other week depending upon the patient's condition, behavior (eating habits) and ability to unload iron.
During de-ironing: blood contains water and other nutrients. Adequate fluid intake guards against dehydration. Patients are encouraged to take a once-a-day multi-vitamin without iron to support the loss of nutrients. Look for vitamins with minerals (except iron) and B complex.
Otherwise, serum ferritin can be checked periodically such as every 3-6 months to determine the patient's unloading pattern.
Most blood donation centers allow one donation every eight weeks. If you are a candidate for maintenance, then a periodic blood donation will suffice. If you are found to need treatment, needing more than one extraction in eight weeks, the attending physician will provide you with the necessary order for additional phlebotomies. Your gastroenterologist or hematologist may refer you back to your family physician for the maintenance phase of your therapy. Afterwards, you may resume a normal, happy healthy life with only a small adjustment to your schedule: a life-saving, blood donation every 8 to 10 weeks.
My Iron Levels
Body iron levels are determined by measuring serum ferritin, fasting serum iron and total iron binding capacity (TIBC). A patient’s transferrin saturation percentage (TS%), an important measure of the body’s capability to bind, transport and maintain safe levels of iron. TS% is calculated by dividing serum iron by TIBC multiplied by 100%. TS% is normally about 35-40%.
Serum ferritin is a measure of stored or contained iron. SF varies by age and gender.
With the exception of infants and newborns, iron overload is suspect when both serum ferritin and TS% are elevated. There are other conditions of high body iron where only the serum ferritin is elevated. These individuals can benefit from periodic blood donation as elevated serum ferritin is a possible early warning that disease is forming.
Hemoglobin indicates the amount of functional iron, that is, the iron that is carrying oxygen to tissues so that organs can function.
What is the role of hemoglobin in phlebotomy?
Hemoglobin value will determine if a person can tolerate phlebotomy to reduce iron levels. If the hemoglobin value is too low, but iron overload is present, iron chelation therapy is used to reduce excessively high iron levels.
For most hemochromatosis patients the hemoglobin levels will rebound and remain in a normal healthy range following phlebotomies or blood donation. Patients with significant iron overload can tolerate frequent treatments because their hemoglobin will rebound very quickly. As the body manufactures new blood to replace that removed, the new liquid acts like a sponge; it draws the iron out of the body tissue (stored in ferritin) to synthesize hemoglobin in the new blood. Once iron becomes part of hemoglobin it can be safely removed with the next treatment.
Hemoglobin levels prior to blood donation should be 12.5g/dL with few exceptions.
Why do I need a phlebotomy?
Phlebotomy reduces excessive and life-threatening levels of body iron. Some patients diagnosed with hemochromatosis have already built up 5 or 10 grams (or more) of excess iron in their bodies. These patients will require aggressive treatment and sometimes will be phlebotomized (or give blood) as often as once or twice a week. For individuals whose iron levels are only modestly elevated, blood can be simply donated every eight weeks without a prescription.
If serum ferritin is less than 1,000ng/mL at the time of diagnosis, the chances of liver cancer is less than 1%. But if diagnosis occurs after serum ferritin has risen above the 1,000 mark, the risk of liver cancer jumps 20-200 fold depending on the individual.
Pretreatment Lab work:
Before the phlebotomy may be done, hemoglobin or hematocrit must be checked. Usually centers have labs on site where the results are forwarded to the attending nurse or phlebotomist. With few exceptions, if the hemoglobin is too low (below 12.5g/dL) the phlebotomy should be postponed to avoid the risk of over-bleeding and unnecessary iron deficiency. Otherwise a person can become iron avid and set themselves up for increased symptoms and struggles to achieve iron balance.
Keep good records:
You may request a copy of lab work from the office manager in charge of records in the doctor's office. Obtaining lab results is highly recommended so that a journal may be compiled. Journals will become a valuable tool if you have to move to another town or seek treatment from another doctor. Knowing about your disorder and understanding the diagnostic process helps to speed recovery and avoid future health setbacks. Iron Disorders Institute provides a free copy of its Personal Health Profile in the Resource Center of the website. These forms are designed to help patients track important information that can be shared with the healthcare provider.
Where are phlebotomy treatments performed?
Phlebotomies might be performed at a blood donation center, as an outpatient in a hospital or even in a doctor's office. Your doctor will probably advise places that provide the treatment. Consider convenience of location, cost to do the phlebotomy, and how responsive the center is to your situation.
In 1999 the FDA declared hemochromatosis blood to be safe for transfusion (to give to others) so long as the hemochromatosis patient qualifies to donate blood as volunteer donors. As a result, many private blood centers and one American Red Cross center offer hemochromatosis donor programs.
The Therapeutic Phlebotomy (TP) Procedure Described:
The process varies slightly depending on the treatment site; following is a general step by step of what takes place.
After the preliminary tests for hemoglobin and hematocrit are finished, a phlebotomist prepares you for the procedure. The phlebotomist can sometimes be a nurse or doctor, but regardless, this individual is trained to perform needle sticks.
If your hemoglobin-hematocrit are sufficient and in accordance with the doctor’s order, you will be prepared for blood removal. Usually you will stretch out on a comfortable recliner chair. The attendant takes your blood pressure, temperature and heart rate (pulse). These numbers will be recorded on your medical chart for future reference.
An elastic band is tied around the upper part of the arm. This helps the vein to stand up. You may have to squeeze a soft rubber ball or make a fist several times to help the vein remain accessible. The nurse then swabs an iodine-based antiseptic on the vein and all around the area near the vein. This is to disinfect the area where the needle is to be inserted and to make certain no bacteria gets into your system during treatment.
A special needle is then inserted into the vein. You might feel a little pinch, but it lasts only a second. A piece of tape is placed over the needle to keep it stable; you just sit back and relax. The needle used is large enough for blood to flow quickly without clotting. Some patients have a fear of needles or vein access difficulties. There are ways to address these issues but they are not routine and require assistance from the healthcare provider and in some cases involve a surgeon. See Phlebotomy Problems and Issues
While the blood flows, some like to bring a headset with earphones or a good book to read during treatment. While relaxing, the blood flows from the needle, into a tube, and then into the blood bag. The blood bag sits onto a scale that measures the weight of the blood. When 500cc (about one-half pint) of blood is removed the donation or phlebotomy is complete. Some blood centers can offer Double Red Cell Apheresis (DRCA) treatment to hemochromatosis patients. DRCA removes more red blood cells but the amount is less than double.
About 250 mgs of iron are removed with each unit of blood removed. The procedure will take as few as ten minutes or as many as thirty; again, it depends on how hydrated you are, your vein access and the thickness of your blood.
After the Treatment:
After the phlebotomy, the nurse will remove the needle from your arm. You may need to keep the area bandaged or you may need to apply mild pressure if bleeding continues. You should rest for about 20 minutes following therapy. This is a precaution to insure you do not get weak or dizzy. You may be given a snack while you are resting and it is suggested you eat something after your therapy.
Your blood will be discarded unless you are enrolled in one the blood centers with an FDA variance to use hemochromatosis blood for transfusion. You can find a list of these centers on our website in the Resource Center.
Between phlebotomies:
To prepare yourself, be sure that you are getting adequate fluids. A daily multi-vitamin without iron is recommended because with treatment iron is removed but so are other nutrients. Nothing replaces a diet with variety but a daily multi can offer benefit during the phlebotomy phase. Be careful about water consumption. Gulping great amounts of water prior to therapy is not wise; you may actually cause yourself to become water intoxicated, a serious condition that can result in death. Hydrate yourself slowly over days; do not wait until the last moment.
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Problems and Issues:
Fear of needles is a powerful deterrent to iron reduction. It is a common complaint expressed by men and women alike. There are not too many alternatives for such a patient, but there are some steps that can help. Taking a light sedative (prescribed by the doctor) can relax a person sufficiently to insert the needle. Having a support person present to distract a nervous patient can be helpful. Listening to music through a headset can also be distracting. Double Red Cell Apheresis (DRCA) is a good choice for many of these patients. One stick allows nearly double the iron extraction saving the person from the anguish or anxiety of twice a week punctures.
Numbing agents such as Emla Cream can help in some cases. These creams temporarily numb the skin allowing the needle to be inserted. Check with your doctor about a prescription but first see if the blood center has any objections to the use of such a product.
Vein access is another issue. When patients require multiple and numerous blood extractions sometimes a chest port is an option to consider. Otherwise, veins in the legs can be used to remove blood.
Since scar tissue can build up significantly over time, a person whose arms are scarred might consider wearing a medical ID bracelet. This can distinguish them from individuals who may be chronic drug abusers.
