EDITORIAL Accepting hereditary hemochromatosis blood donors: ask not why, ask why not
H
ereditary hemochromatosis (HH) is an inherited disorder of iron metabolism, treated by regular therapeutic phlebotomy to prevent iron accumulation and organ damage. Recognized as a potential source of blood for allogeneic transfusion for years,1 therapeutic donations from persons with HH are accepted in many countries but still resisted in others because of lingering concerns about safety, operational compliance, or cost.2 Safety concerns historically stem from the possibility of creating an incentive to donate blood for free rather than to pay for therapeutic phlebotomy, possibly encouraging HH donors to deny risk factors for infectious diseases. In the Final Rule that became effective in May 2016, the US Food and Drug Administration codified the requirements for HH donors in the Code of Federal Regulations (CFR), thus eliminating the need for a variance to collect whole blood more frequently than every 8 weeks (or double red blood cells more frequently than every 16 weeks) and distribute units without special labeling from HH donors who meet all eligibility requirements. Notably, the CFR retains the requirement for obtaining a prescription for therapeutic phlebotomy from a licensed health care provider and performing therapeutic phlebotomy free of charge [21 CFR 630.15(a)(2)]. Therefore, the question of the safety of HH blood in this context is a timely one for blood collectors and transfusion services. In this issue of TRANSFUSION, Hoad and coworkers3 address the issue of infectious risk in blood donated from HH donors in a retrospective cohort study of all whole blood donations at the Australian Red Cross Blood Service in a 3-year period comparing therapeutic HH donors and voluntary whole blood donors. The authors examined postdonation notification of infectious illnesses, bacterial contamination screening results, and positive tests for blood-borne viruses in therapeutic and voluntary nontherapeutic whole blood donors. The strengths of the study are its impressive scale, including more than 100,000 donations from almost 12,000 HH donors and more than 2.5 million donations from more than 460,000 voluntary donors. Importantly, this institution provided free doi:10.1111/trf.13919 Published 2016. This article is a U.S. Government work and is in the public domain in the USA. TRANSFUSION 2016;56;2907–2909
phlebotomy to HH donors who were not eligible to donate for transfusion, as a safety measure to remove any perceived incentive to deny risk factors about transfusion-transmissible infection (TTI). Furthermore, the study included donors in the induction phase (ironlowering phase) as well as those in the maintenance phase of therapeutic phlebotomy, which is not a universal practice. The authors report a lower risk of TTI in therapeutic HH donations intended for transfusion compared to voluntary donations and no significant difference in TTI rates when donations destined for product discard due to self-declared risk factors are included in the analysis. In addition, bacterial contamination of pooled platelet collections and self-reported postdonation illness are not different among HH donors compared to voluntary whole blood donors. Most HH donations are from repeat donors, and the authors did not adjust their analysis for first-time donation status, which they identified as a limitation, but is appropriate for a pragmatic comparison of the safety of HH donors compared to the general voluntary pool. The study supports the conclusion that therapeutic HH donors undergoing depletion and maintenance therapeutic phlebotomy are a safe and acceptable source of donated whole blood with a low infectious disease risk profile. These safety data directly assuage the niggling concern about collecting blood from HH donors that has been a source of debate for some time. Since the molecular basis of the disease was elucidated in 1996, it has been posited that the condition itself poses no harm to the recipient. The question concerns the motives of the HH donor to give blood and the possibility of incentive to withhold information from blood establishments about infectious risk factors.4 Recalling that it was the discontinuation of remuneration for blood donation that first significantly reduced transmissiontransmitted hepatitis, some blood establishments still might be reluctant to accept blood from “motivated” donors. However, the incentive in the case of HH donors is for phlebotomy, not necessarily for allogeneic blood donation. As long as the availability of therapeutic phlebotomy is kept independent from the disposition of the blood, by providing phlebotomy free of charge to eligible and ineligible HH donors alike, the point becomes moot. The National Institutes of Health (NIH) experience, like the experience of the Australian Red Cross and Volume 56, December 2016 TRANSFUSION 2907
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others, is that that these donors are safe and they contribute substantially to the supply. NIH has been collecting blood from HH donors for transfusion and for research purposes since 2001. Currently, HH donors comprise approximately 7% of the donor base but provide 11% of the allogeneic blood supply. Hoad and colleagues likewise document in this report substantial contribution of therapeutic donors as 2.72% of their donor base but 4.44% of all whole blood donations. In the 16-year NIH experience, HH donors have had no incident seroconversions for agents of transfusiontransmissible disease.5 This observation is not surprising, since HH donors are more likely to be frequent long-term donors, who have been shown to have a lower risk of TTI than first-time donors.6 There is perhaps another moral question on the flip side that is less often considered: the issue of wasting a valuable resource given its proven suitability,7 particularly in the face of perennial blood shortages. Other authors have demonstrated the financial feasibility and benefit of collecting HH blood and estimated how much suitable blood is wasted by not utilizing blood from HH donors for transfusion.8 Hoad and colleagues also raise the ethical principle of “do no harm,” considering that HH donors are much less susceptible to blood donation-related iron deficiency and related adverse consequences than non-HH donors. Furthermore, most HH donors are middle-aged men (mean, 50 years) who have lower rates of immediate complications after blood donation compared to the rates of syncope and related injuries among 16- to 18-year-old blood donors at high schools. Yet, some US blood centers have raised concerns about operational issues and medical oversight of HH donors, as obstacles to launching or maintaining HH donor programs. Although not directly addressed in the current study, aspects of the Australian program and other programs are noteworthy in this regard. Hoad and colleagues describe that HH donors must meet the donor health eligibility requirements applied to voluntary whole blood donors, to protect their safety. They also use an electronic referral mechanism for HH patients, allowing a referring physician to enter patient details and receive a real-time response regarding eligibility. This system likely ensures compliance and facilitates collaboration with the treating physician, since the blood center is providing the prescribed course of therapeutic phlebotomy, but not assuming responsibility for the individual’s ongoing medical care. Finally, all blood centers must have robust systems for physical quarantine and electronic controls to manage unsuitable units and postdonation information, at all stages of manufacturing, so concerns about regulatory compliance should be settled and easily addressed in standard operating procedures. 2908 TRANSFUSION Volume 56, December 2016
An additional benefit of the HH donor program at NIH is that it can be extended to donors who are temporarily deferred from allogeneic donation (e.g., due to travel) who provide a good resource for blood for in vitro research. The HH donor program is important for donor satisfaction and community relations. HH donors are glad to have their blood used either for allogeneic transfusion or for research, rather than have it discarded.3,9 An added incentive for blood centers as yet unquantified is the self-perpetuating recruitment and community outreach—we estimate that each HH donor brings in a few more to our program each year. In summary, the results of the study by Hoad and colleagues support the assertion that eligible HH donors are a safe source of blood for transfusion. The HH blood donor pool is a willing but underutilized resource for clinical and research purposes. The expectation now is not for a few blood services to justify why they have successful HH donor programs but for the rest to examine why they do not and rectify this deficiency. CONFLICT OF INTEREST The authors have disclosed no conflicts of interest. The views expressed are the authors’ own and do not represent the National Institutes of Health, the Department of Health and Human Services, or the U.S. Federal government.
Kamille A. West, MD e-mail:
[email protected] Anne F. Eder, MD, PhD Department of Transfusion Medicine Blood Services Section National Institutes of Health Clinical Center Bethesda, MD
REFERENCES 1. Barton J, Grindon A, Barton N, et al. Hemochromatosis probands as blood donors. Transfusion 1999;39:578-85. 2. Pauwels NS, De Buck E, Compernolle V, et al. Worldwide policies on haemochromatosis and blood donation: a survey among blood services. Vox Sang 2013;105:121-8. 3. Hoad V, Bentley P, Bell B, et al. The infectious disease blood safety risk of Australian hemochromatosis donations. Transfusion 2016;56:2934-40. 4. Pennings G. Demanding pure motives for donation: the moral acceptability of blood donations by haemochromatosis patients. J Med Ethics 2005;31:69-72. 5. Leitman SF, Browning JN, Yau YY, et al. Hemochromatosis subjects as allogeneic blood donors: a prospective study. Transfusion 2003;43:1538-44. 6. Dorsey KA, Moritz ED, Steele WR, et al. A comparison of human immunodeficiency virus, hepatitis C virus, hepatitis B virus and human T-lymphotropic virus marker rates
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for directed versus volunteer blood donations to the American Red Cross during 2005 to 2010. Transfusion 2013;53:1250-6. 7. De Buck E, Pauwels NS, Dieltjens T, et al. Is blood of uncomplicated hemochromatosis patients safe and effec-
8. Gribble DM, Chaffin DJ, Bryant BJ. Cost-effectiveness of FDA variance for blood collection from individuals with hereditary hemochromatosis at a 398-bed hospital-based donor center. Immunohematology 2009;25:170-3. 9. Marrow B, Clarkson J, Chapman CE, et al. Facilitation of
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