Past, Present, and Future of Donor Iron Deficiency

Donating blood is an essential community service that saves lives. Because donors are healthy volunteers, several safety precautions are put in place to maintain their well-being. For example, there are restrictions on how often one can donate different types of blood products, to ensure that the donor has adequate time to recover.

Blood Product Donated	Donation Interval
Whole Blood	56 days/8 weeks
1 unit of red blood cells	56 days/8 weeks
2 units of red blood cells	112 days/16 weeks
Platelets	7 days/1 week
Plasma	48 hours/2 days (no more than twice in 7 days)

One common issue of donor safety is iron depletion or deficiency. A donation of one unit of whole blood contains about 250 mg of iron, or about 25% of the iron stores in a typical adult male. For menstruating individuals, this percentage is higher. Loss of iron stores leads first to iron depletion, which is defined as iron levels <26 ng/dL, then to iron deficiency, which is defined as iron levels <19 ng/dL. If iron deficiency is not corrected, it can reduce production of red blood cells and lead to anemia, which is defined as hemoglobin levels < 13.5 g/dL in males and <12.0 g/dL in females.

Blood donation centers routinely test hemoglobin levels prior to blood donation. This can uncover anemia and an anemic donor will be deferred for donor safety. However, iron levels are generally determined with a ferritin level, which is not routinely performed at donor centers. Studies show that while anemia is present in 4.2% of all donors and 6.2% of female donors, iron deficiency is more prevalent at 13.6% of all donors, and 22.6% of female donors [1].

As transfusion medicine physicians, we care about the iron levels of our donors for two main reasons. First, we want to maintain the well-being of our healthy volunteer donors. Iron is an essential nutrient and evidence suggests it is critical not just for the production of red blood cells, but also for brain maturation and development as well as healthy pregnancies [2]. Second, we want to act as good stewards of our blood supply. Approximately 8-12% of all potential blood donations are deferred due to iron deficiency, and mitigating iron deficiency could reduce deferrals by 66% [2].

A great deal of research has been done to investigate iron deficiency in donors. First, the HEIRS study found that iron supplementation in the first 8 weeks after donation can help donors recover faster [3]. Second, the STRIDE study found that testing for ferritin levels at donation and providing written documentation of the result is as effective as prescribing iron supplementation [4]. Finally, the CHILL study found that adolescent donors are more at risk of iron deficiency than their adult counterparts [5].

Currently, the AABB recommends that blood donation centers adopt the following three strategies to mitigate iron deficiency in their donors. First, that they provide educational materials about iron deficiency and discuss its impacts, particularly in at risk subgroups of donors like adolescents and individuals who menstruate. Second, that they provide direct intervention either to all donors or to at risk subgroups by testing for ferritin levels, providing iron tablets or vouchers for iron supplements, or spacing out donation intervals to allow for adequate recovery. Finally, that donor centers implement monitoring of donor iron deficiency after implementing one or both of the above strategies.

There remain some unanswered questions in the field of donor iron deficiency. First, what dose of iron supplementation is appropriate? In the original HEIRS study, donors were supplemented with daily iron doses. In the time since that study, evidence has emerged that daily iron dosing actually inhibits the absorption of iron by triggering the release of hepcidin [6, 7], and current recommendations are to dose iron every other day or even three times per week.

Another unanswered question is the risk of iron supplementation itself. Several recent studies have found a link between iron supplementation and increased risk of bacteremia and bacterial seeding [8]. However, these studies were done on healthy donors taking iron supplements and did not include those with iron deficiency in the study population. Whether these results can be extrapolated to iron deficient donors remains to be seen. To date, studies of donor iron deficiency have not tracked infection, hospitalization, or death as an outcome of donor iron supplementation.

In summary, blood donation can lead to iron deficiency, and iron supplementation of donors is a cost-effective intervention to maintain donor health and the blood supply. However, there may be room for improvement in the current guidelines and further studies would certainly be indicated.

References:

1.       Salvin, H.E., Pasricha, S.R., Marks, D.C. and Speedy, J., 2014. Iron deficiency in blood donors: a national cross‐sectional study. Transfusion, 54(10), pp.2434-2444.

2.       Smith GA, Fisher SA, Doree C, Di Angelantonio E, Roberts DJ. Oral or parenteral iron supplementation to reduce deferral, iron deficiency and/or anaemia in blood donors. Cochrane Database of Systematic Reviews. 2014(7).

3.       Kiss JE, Brambilla D, Glynn SA, Mast AE, Spencer BR, Stone M, Kleinman SH, Cable RG; National Heart, Lung, and Blood Institute (NHLBI) Recipient Epidemiology and Donor Evaluation Study–III (REDS-III). Oral iron supplementation after blood donation: a randomized clinical trial. JAMA. 2015 Feb 10;313(6):575-83. doi: 10.1001/jama.2015.119. PMID: 25668261; PMCID: PMC5094173.

4.       Mast AE, Bialkowski W, Bryant BJ, Wright DJ, Birch R, Kiss JE, D'Andrea P, Cable RG, Spencer BR. A randomized, blinded, placebo-controlled trial of education and iron supplementation for mitigation of iron deficiency in regular blood donors. Transfusion. 2016 Jun;56(6 Pt 2):1588-97. doi: 10.1111/trf.13469. Epub 2016 Jan 26. PMID: 26813849; PMCID: PMC4905782.

5.       Patel, E. U., White, J. L., Bloch, E. M., Grabowski, M. K., Gehrie, E. A., Lokhandwala, P. M., Brunker, P., Goel, R., Shaz, B. H., Ness, P. M., & Tobian, A. (2019). Association of blood donation with iron deficiency among adolescent and adult females in the United States: a nationally representative study. Transfusion, 59(5), 1723–1733. https://doi.org/10.1111/trf.15179

6.       Moretti, D., Goede, J. S., Zeder, C., Jiskra, M., Chatzinakou, V., Tjalsma, H., ... & Zimmermann, M. B. (2015). Oral iron supplements increase hepcidin and decrease iron absorption from daily or twice-daily doses in iron-depleted young women. Blood, The Journal of the American Society of Hematology, 126(17), 1981-1989.

7.       Nicole U Stoffel, Colin I Cercamondi, Gary Brittenham, Christophe Zeder, Anneke J Geurts-Moespot, Dorine W Swinkels, Diego Moretti, Michael B Zimmermann. Iron absorption from oral iron supplements given on consecutive versus alternate days and as single morning doses versus twice-daily split dosing in iron-depleted women: two open-label, randomised controlled trials. The Lancet Haematology, Volume 4, Issue 11, 2017, Pages e524-e533, https://doi.org/10.1016/S2352-3026(17)30182-5.

8.       Cross, J. H., Bradbury, R. S., Fulford, A. J., Jallow, A. T., Wegmüller, R., Prentice, A. M., & Cerami, C. (2015). Oral iron acutely elevates bacterial growth in human serum. Scientific reports, 5, 16670. https://doi.org/10.1038/srep16670