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Protecting the blood donor: ferritin-based intervals to improve donor health

Laura Infanti

Lancet Published: June 13, 2024

DOI: https://doi.org/10.1016/S0140-6736(24)01212-1

Strict eligibility criteria and the ageing of the general population are among the main factors limiting blood donor availability,¹ and render the retention of experienced donors and the acquisition of new volunteers a demanding task. Also, a temporary inability to give blood (eg, due to recent travel or a medical condition) can be a reason for abandoning blood donation permanently.² Blood establishments are constantly making efforts to counteract blood shortages and the overall declining trends in donations.

In this context, low haemoglobin concentration, which is the most common reason for donation deferral, is a key risk factor for the loss of active volunteers. Due to the loss of 220–250 mg of iron with each whole-blood donation, iron deficiency with or without anaemia is the most important side-effect of blood donation.³ In 2012, both WHO⁴ and the American Association of Blood Banks⁵ released recommendations for monitoring ferritin concentrations in blood donors, but ferritin concentration measurement remains only an optional tool for assessing donor eligibility.

A strong predictor of iron deficiency is the interval between donations. For healthy individuals not taking iron supplementation, recovering iron stores after the drawing of 450–500 mL of blood requires at least 180 days.⁶ Several observational studies questioned the minimal donation interval allowed by regulation as being too short for preventing iron deprivation,⁷ and the randomised INTERVAL study showed that shorter donation intervals, although increasing blood procurement, resulted in more frequent haemoglobin deferrals.⁸ Indeed, ensuring a sufficient blood supply and protecting healthy volunteers at the same time is very difficult. Thus, despite available evidence, European and US regulations permit whole-blood donations up to once every 56 days for both sexes, although at a maximum of six donations per year for male donors and four donations per year for female donors in Europe.

Monitoring of ferritin concentrations enables targeted counselling of donors regarding the type (eg, platelet or plasma instead of whole blood) and the frequency of donation for limiting iron loss.⁹

Increasing numbers of blood establishments have ferritin-based programmes of donor care,¹⁰ but corresponding national policies have been implemented in very few countries to date, and regular ferritin concentration testing requires operational and financial efforts that can overstrain the resources of most collection centres even in high-income countries. Blood establishments need feasible concepts for the management of iron deficiency, considering that ferritin concentrations as low as 10 ng/mL can be the minimal acceptable limit in blood donors.¹¹ Medical judgement is required in interpreting low ferritin concentrations in donors of different ages and by sex and in considering the possible presence of an undiagnosed associated medical condition or of important effects of iron deprivation.

In The Lancet, Amber Meulenbeld and colleagues¹² present the results of the first randomised study on the effectiveness of ferritin-guided donation intervals that was conducted nationwide in the Netherlands from September, 2017, to November, 2020. Ferritin concentration was tested at screening in first-time donors and post-donation in repeat donors at every fifth donation, triggering a postponement of the subsequent donation for 6 months if concentrations were 15–30 ng/mL or 12 months if they were below 15 ng/mL. The 138 blood donation centres in the country are grouped geographically into 29 clusters, which were randomly assigned to four groups, and the ferritin-guided policy was progressively introduced (in addition to haemoglobin-based deferral policies) across all centres in a stepped-wedged design. Controls were the sites that still followed conventional haemoglobin-based deferral policies only. In each group, cross-sectional ferritin measurements were done on frozen samples at baseline (2 months before implementation), once midway through implementation, and then 1 week and 1 year after the policy was fully implemented. The primary outcomes were concentrations of haemoglobin and ferritin, haemoglobin deferral, and iron deficiency, which were analysed in the overall population and by sex and menopausal status (with female donors younger than 45 years defined as premenopausal and female donors aged 45 years and older defined as postmenopausal). The iron deficiency symptoms and donor return within 6 months were the secondary outcomes.

Over the 38-month study period, 412 888 whole-blood donors visited a donation centre, and samples were assessed from 37 621 donations from 36 099 donors. The ferritin-guided strategy increased both ferritin and haemoglobin concentrations and lowered the proportion of donors with iron deficiency, regardless of sex and menopausal status; however, haemoglobin-based deferral only decreased in male donors, with no significant difference seen for premenopausal or postmenopausal female donors.¹² The important downside of the strategy was a steady decrease in return of donors within 6 months, which decreased by 36–38 months after implementation compared with pre-implementation in male donors (odds ratio 0·50 [95% CI 0·41–0·61; p<0·0001]) and postmenopausal female donors (0·67 [0·52–0·87; p=0·0025]), although this was not found for premenopausal female donors (1·03 [0·84–1·25; p=0·78]).

The study was rigorously designed and conducted, a large amount of qualitative data was collected, and the results have huge practical implications. A possible drawback of the evaluated strategy is a higher risk of losing donors after postponing a subsequent donation. Also, an unanswered question is whether simply extending donation intervals would sufficiently protect volunteers, which is discussed by the authors.¹² Nonetheless, this strategy shows great promise for protecting donor health. Further studies could address the efficacy of combining longer intervals and iron supplementation, which would be a more costly and laborious approach, but could more efficiently counteract donor loss due to low haemoglobin concentrations.

Notwithstanding that conducting such a large-scale trial presupposes the availability of adequate resources and a highly organised operational setting such as that of Sanquin, the blood establishment of the Netherlands, the study findings are motivating. It provides definitive evidence of a feasible and efficacious ferritin-driven strategy for protecting blood donors, which is a key factor for securing blood supply in the future. Expanding the blood donor base to increase the overall number of active donors should be the goal of blood establishments, such that donors can donate less frequently and, hopefully, longer, while remaining in good health.