The strategies to reduce iron deficiency in blood donors randomized trial: design, enrolment and early retention

Abstract

Background and Objectives Repeated blood donation produces iron deficiency. Changes in dietary iron intake do not prevent donation-induced iron deficiency. Prolonging the interdonation interval or using oral iron supplements can mitigate donation-induced iron deficiency. The most effective operational methods for reducing iron deficiency in donors are unknown. Materials and Methods ‘Strategies To Reduce Iron Deficiency’ (STRIDE) was a two-year, randomized, placebo-controlled study in blood donors. 692 donors were randomized into one of two educational groups or one of three interventional groups. Donors randomized to educational groups either received letters thanking them for donating, or, suggesting iron supplements or delayed donation if they had low ferritin. Donors randomized to interventional groups either received placebo, 19-mg or 38-mg iron pills. Results Iron deficient erythropoiesis was present in 52.7% of males and 74.6% of females at enrolment. Adverse events within 60 days of enrolment were primarily mild gastrointestinal symptoms (64%). The incidence of de-enrolment within 60 days was more common in the interventional groups than in the educational groups (P = 0.002), but not more common in those receiving iron than placebo (P = 0.68). Conclusion The prevalence of iron deficient erythropoiesis in donors enrolled in the STRIDE study is comparable to previously described cohorts of regular blood donors. De-enrolment within 60 days was higher for donors receiving tablets, although no more common in donors receiving iron than placebo.

Frequent blood donations alter susceptibility of red blood cells to storage‐ and stress‐induced hemolysis

“…For example, repeated phlebotomy in frequent blood donors may severely deplete iron stores and subsequently interfere with normal erythropoiesis. 5,6 Recent investigations of frequent blood donors have focused primarily on preventative care against iron deficiency anemia, [7][8][9][10][11][12] with limited understanding regarding the impact of frequent donations on RBC characteristics and resilience to cold storage.…”

The operational implications of donor behaviors following enrollment in STRIDE (Strategies to Reduce Iron Deficiency in blood donors)

“…The study was designed to evaluate an educational intervention and an iron‐supplementation intervention, each with appropriate controls. As previously described, eligible frequent whole blood or double red blood cell (DRC) donors who were not taking iron supplements were recruited at an enrollment donation. Donors agreed to continue to donate whole blood or DRCs at their previous frequency and, if assigned to the blinded pill arms, not to take any self‐administered iron supplements.…”

“…Donors in the pill groups were sent a bottle of pills and instructions after each donation. Details of the blinding method and management of side effects have been previously reported . To allow for compliance assessment, donors were asked to return unused pills or empty bottles from the previous mailing in a postage‐paid envelope.…”

“…The Strategies to Reduce Iron Deficiency (STRIDE) study was a multicenter, randomized, blinded, and placebo‐controlled study investigating the relative efficacy of two approaches for mitigating donor iron deficiency in frequent blood donors (http://clinicaltrials.gov identifier NCT02245321) . Randomization to one of five groups, representing an educational or iron supplementation intervention, allowed for comparison of alternate strategies that are operationally feasible for most blood centers.…”

Putting donor health first in strategies to mitigate donor iron deficiency

“…Thus, donors with a ferritin level of not more than 12 ng/mL have severe iron deficiency with no iron in the marrow available for synthesis of new RBCs. During our studies of frequent donors, we have routinely observed subjects who passed the Hb screen and donated 1 unit of blood, only later to find that their predonation ferritin level was not more than 12 ng/mL, confirming that Hb is a poor marker for iron deficiency in blood donors. While ferritin level of not more than 12 ng/mL is a highly specific marker for iron deficiency, it is not a particularly sensitive marker for iron deficiency.…”