5.1 Introduction

The US Food and Drug Administration (FDA) mandates that blood donors wait 56 days between whole blood donations, but this one-size-fits all inter-donation interval (IDI) may be too short for some repeat donors to replenish iron stores [139]. Observational studies show that frequent blood donation can cause or exacerbate iron deficiency, with higher incidence among teen donors and premenopausal women [21–26]. Potential donors are screened using fingerstick hemoglobin or hematocrit tests and deferred if levels are below a minimum cutoff. Such hemoglobin deferrals prevent some collections from iron deficient donors but also consume time and resources from both donor and blood center, decreasing donor satisfaction and likelihood of future donations [140]. Because fingerstick hemoglobin is an unreliable indicator of true iron stores, many donors qualify to donate despite having low or absent underlying iron stores [24]. More reliable measures of iron status include ferritin, zinc protoporphyrin, soluble transferrin receptor, and hepcidin, but these are more costly to measure and not available as point of care tests [141]. Past studies have identified several factors that increase risk of iron deficiency among blood donors. The Danish Blood Donor Study found that sex, menopause status, and donation history were the strongest predictors of iron deficiency among donors, but weight, age, vitamin use, and diet were also significant [25]. Other studies have come to similar conclusions [21–24,26].

Several interventions are available to manage iron deficiency in blood donors, which blood collectors and regulators must assess in terms of their effectiveness, cost, implementation complexity, and impact on ability to meet demand for donated blood. Many countries have longer minimum IDIs than the United States, and some require a longer IDI for female donors as compared to male donors. A large randomized trial in the U.K. found that a longer IDI reduced the frequency of hemoglobin deferrals, low- and absent-iron donations, and self-reported symptoms associated with iron deficiency [27]. Because most blood donations come from repeat donors (72% of all U.S. donations in 2015 [142]), longer IDIs could make it difficult for blood collectors to meet demand. Some blood centers test donors for ferritin, a more reliable indicator of underlying iron stores as compared to fingerstick hemoglobin, and recommend a longer IDI for donors with low ferritin. A Canadian study found that donors informed of low-ferritin results had a lower return rate and a higher ferritin on return [28], and a large U.S. blood collector has instituted ferritin testing for teenage donors [29]. At present, ferritin testing is costly and cannot be done at ‘point-of-care’, meaning that blood centers learn of pre-existing iron deficiency after the additional insult of further iron loss from blood donation. Other blood centers have experimented with providing or recommending iron supplementation to donors [30,31], and a U.S. clinical trial estimated that iron supplementation could reduce post-donation time to 80% iron stores recovery from 11-23 weeks to 4-5 weeks [31]. Ferritin testing can be used to target recommendations for iron supplementation, and one study found that the majority of low-ferritin donors preferred taking supplemental iron over lengthening their IDI [32]. However, iron supplements can induce gastrointestinal distress [33], and some blood collectors worry about liability if donors experience adverse outcomes.

One unexplored intervention is tailoring the minimum IDI based on each donor’s risk of iron-related adverse outcomes. In this analysis, we used data from the REDS-II Donor Iron Status Evaluation (RISE) study [21] to develop a prediction model that estimated how a donor’s risk of iron-related adverse outcomes would develop as a function of the time until a subsequent donation attempt. We then simulated the impact of prescribing a tailored minimum IDI based on each donor’s estimated risk and compared the estimated donation yield and number of adverse outcomes to the baseline and to alternative interventions for donors in the RISE cohort.