Paul C. Adams

Transferrin saturation (TS) has been recommended for screening for hemochromatosis ( 1). It is widely available, and results may be increased even in young adults with hemochromatosis. The TS assay is a two-step assay with serum iron in the numerator and total iron-binding capacity, unsaturated iron-binding capacity (UIBC), or serum transferrin in the denominator. Serum iron/(serum iron + UIBC) equals the TS. In a previous study, we compared UIBC to TS as a screening test for C282Y hemochromatosis in a population of asymptomatic voluntary blood donors ( 2). Because blood donation could potentially affect iron status, we have reevaluated TS and UIBC in referred hemochromatosis patients and used first-time blood donors as control cases (n = 386, all wild type by C282Y genotyping).

Early diagnosis and treatment of hemochromatosis is essential to prevent organ damage. Screening strategies to detect early hemochromatosis include testing for iron overload and/or genetic testing. Voluntary blood donors numbering 5,211 were screened with unbound iron-binding capacity (UIBC), transferrin saturation (TS), and genetic testing for the C282Y mutation of the HFE gene. The study found 16 C282Y homozygotes (1 in 327), 69 compound heterozygotes, 371 simple heterozygotes, and 4,755 normals. There were 5 men and 11 women homozygotes with a mean age of 42, range 28 to 57. Mean UIBC (24 ± 7 μmol/L) and TS (48% ± 17%) in homozygotes were significantly different from compound heterozygotes, simple heterozygotes, and normals (ANOVA). Only 3 homozygotes had an elevated serum ferritin. Family studies found an additional 4 iron-loaded homozygotes. Optimal thresholds were ≤28 μmol/L for UIBC and ≥46% for TS. Receiver operating characteristic (ROC) curve analysis showed an area under the curve for UIBC of 0.93 (0.85-1.0, 95% confidence interval), and for TS of 0.83 (0.7-0.95). Screening with UIBC to preselect those for genotyping is a cost-efficient strategy for population screening for hemochromatosis.

A 19 year old man underwent orthotopic liver and intestinal transplantation in January 1997 for the treatment of short bowel syndrome secondary to a mid gut volvulus with resection and cholestatic liver disease resulting from total parenteral nutrition. The organ donor was an 18 year old woman posthumously discovered to be a C282Y homozygote for haemochromatosis.

Hemochromatosis heterozygotes may be predisposed to end-stage liver disease from other causes. The aims of this study were to determine the prevalence of the hemochromatosis mutation, C282Y, in end-stage liver disease and to determine if transplantation of C282Y heterozygous livers adversely affected survival. The C282Y status of patients who underwent hepatic transplantation and, whenever possible, their donors, was determined and correlated with hepatic iron status. Survival was compared in patients who received livers from heterozygotes and normals. Prevalence of C282Y in recipients was compared with 5,211 voluntary blood donors. Twenty-six C282Y heterozygotes were detected among 304 transplant recipients (8.6%) compared with a prevalence of 8.4% in blood donors. Six of 26 heterozygous recipients (23%) had ≥2+ iron staining in their explanted livers compared with 40 of 277 wild-type livers (14%) (P= ns). There was no significant difference in mean hepatic iron concentration between C282Y heterozygotes and wild-type explanted livers with ≥2+ iron staining. Seven of 31 patients (23%) with alcoholic liver disease were C282Y heterozygotes. Twenty-four heterozygotes were detected in 141 donors (17.0%). Survival did not differ between recipients who received heterozygous or normal livers. The prevalence of C282Y heterozygotes in patients requiring liver transplantation does not differ significantly from the general population. Heterozygotes are not at increased risk of developing end-stage liver disease. Transplantation of C282Y heterozygous livers is a safe, effective practice.

BACKGROUND: Hereditary hemochromatosis patients are excluded in many countries as voluntary blood donors. In 1991, changes in the Canadian Red Cross policy allowed healthy hemochromatosis patients to become voluntary donors.STUDY DESIGN AND METHODS: The medical histories of 208 hemochromatosis patients were evaluated for eligibility for blood donation from a large prospective database of hemochromatosis patients. A survey that determined the success or exclusion of 81 patients for blood donation and the reasons for their exclusion based on Canadian Red Cross donor exclusion criteria was analyzed.RESULTS: Of 208 hemochromatosis patients, 140 (67%) were eligible for blood donation. Criteria for exclusion were other illnesses excluded by Canadian Red Cross criteria and the use of contraindicated medications. Fifty-one per cent of patients had attempted to donate blood, with only 7% being successful.CONCLUSIONS: A large number of potential blood donors are excluded from blood donation inappropriately despite changes in eligibility criteria to the contrary. Further public and health education is needed to increase awareness and, thus, increase blood donation by potential donors.