Introduction

Hereditary hemochromatosis with serum ferritin (SF) greater than 1000µg/L at diagnosis has been associated with symptoms and end-organ damage from iron overload. However, clinical manifestation of iron overload is much less frequently observed when only a moderate iron overload of SF 1000µg/L or less is present at diagnosis. Data to guide optimal management with venesection of patients with moderate overload is currently limited and many clinical guidelines do not distinguish the degree of iron overload at presentation in their management recommendations. Since 2013, patients with hemochromatosis who present to our center with a SF of less than 1000µg/L without end organ dysfunction have been venesected to a target of <100µg/L before discharge without maintenance venesections. Patients and their primary care clinicians are advised to re-refer if iron reaccumulates to SF ≥500µg/L or if end-organ damage occurs. Here we present our experience in this practical approach in managing patients with moderate iron overload.

Method

Patients referred to our center for management of HFE mutated haemochromatosis between 1 January 2013 and 31 December 2017 were included (recent cohort). These patients were discharged after initial iron reduction. A second cohort of patients managed between 1 December 2001 to 31 December 2003 was also included for comparison (historic cohort). This historic cohort initially received maintenance venesections before being discharged in 2013, following a change in our policy. Patients were identified using the departmental electronic database and data was extracted from the patient electronic record. Time to re-referral was measured from the date of last venesection prior to discharge to the date of re-commencing venesection or referral to other services for iron related complications. Patients who had not been re-referred for resuming venesection or to other services for iron-overload complications were censored on 1 July 2020.

Result

A total of 109 patients were included for analysis (historic cohort: 54; recent cohort: 55). The median age was 45 (range: 45 - 81), and 74 (67.9%) patients were male. Homozygote C282Y mutation was the most common genotype (74.3%), followed by compound heterozygotes (C282Y/H65D or C282Y/S63C, 23.9%). The median SF prior to venesection was 539µg/L (range: 146 - 968), and a median of 8 venesections were required initially to achieve a SF of <100µg/L (range: 1-27). There was no significant difference between the two cohorts in baseline patient characteristics apart from gender, where the proportion of male patients was lower in the historic cohort (56% vs 80%, p = 0.006). The median time to re-referral was 151.5 months and there was no difference between the two cohorts (p = 0.507). The estimated rate of re-referral at 5 and 10 year was 36% and 44%, respectively. Compound heterozygotes had a lower rate of re-referral compared to homozygotes C282Y, albeit not statistically significant (p = 0.069). Age, gender, presenting SF (<500µg/L vs >500µg/L), and number of initial venesections needed for de-ironing (quartiles) were not predictive of re-referral.

Conclusion

Hereditary hemochromatosis patients who present with only a moderate iron overload at the time of diagnosis could be discharged to primary care following initial iron reduction. A significant proportion of patients do not accumulate significant levels of iron following cessation of venesection. The rate and pattern of iron re-accumulation was similar irrespective of whether patients received a period of maintenance venesection prior to discharge.

Disclosures

Chan:Amgen: Other: TRAVEL, ACCOMODATIONS, EXPENSES (paid by any for-profit health care company); Celgene: Other: TRAVEL, ACCOMODATIONS, EXPENSES (paid by any for-profit health care company); Roche: Other: TRAVEL, ACCOMODATIONS, EXPENSES (paid by any for-profit health care company); AbbVie: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding, Speakers Bureau.

Author notes

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Asterisk with author names denotes non-ASH members.