Researchers in the Netherlands have published their findings in The Lancet from a stepped-wedge cluster-randomized trial exploring the impact of ferritin-guided donation intervals on the health of whole-blood donors. The ferritin-guided donation intervals paper explained that, “29 [geographical] clusters were randomly assigned to four randomi[z]ation groups. The stepped-wedge design involved random and sequential crossover of clusters from the control (existing policy) to the intervention (ferritin-guided donation intervals) by randomi[z]ation group over the course of 24 months, until all clusters were exposed to the intervention.”
For this 38-month ferritin-guided donation interval study, [t]he intervention entailed ferritin-guided donation intervals in addition to the existing h[e]moglobin screening and regular donation intervals of 56 days and 122 days for male and female donors, respectively.” Six-month deferrals took place for donors whose ferritin concentration was 30 ng/mL or lower and 12-months for individuals whose concentration was below 15 ng/mL. The authors noted that they chose a, “12-month interval for iron deficient donors to allow donors to replenish their concentrations to levels higher than before donation.” The primary outcomes are described as, “ferritin and h[e]moglobin concentrations, h[e]moglobin deferral, and iron deficiency. Secondary outcomes were donor return within 6 months and iron deficiency symptoms assessed through questionnaires.”
The ferritin-guided donation interval study found that, “[t]he prevalence of iron deficiency and h[e]moglobin deferral decreased after implementation of the policy. Compared with no implementation and 0–5 months after implementation (hereafter referred to as pre-implementation), the intervention was associated with a 1.51 ng/mL higher mean ferritin concentration (0.18 log10 ng/mL [95 percent CI 0.15–0.22; p<0·0001]) and 0.30 g/dL (95 percent CI 0.22–0.38; p<0·0001) higher mean h[e]moglobin concentration at 36–38 months after implementation in male donors.” Additionally, the researchers of the ferritin-guided donation interval study discovered that, “premenopausal and postmenopausal female donors, mean ferritin concentration increased by 1.26 ng/mL (0.10 log10 ng/mL [95 percent CI 0.06–0.15; p<0·0001]) and 1.48 ng/mL (0.17 log10 ng/mL [0.12–0.21; p<0·0001]) at 36–38 months after implementation, respectively, compared with pre-implementation. Mean h[e]moglobin increased by 0.12 g/dL (95 percent CI 0.03–0.20; p=0.0074) and 0.16 g/dL (0·05–0·27; p=0·0044) at 36–38 months after implementation in premenopausal and postmenopausal female donors, respectively.” Both male and female donors experienced “significant decreases in iron deficiency by 36-38 months” following implementation compared with pre-implementation.
While male donors also saw significant decreases in hemoglobin-based deferrals after implementation, there was “no significant difference” in female donors regarding hemoglobin deferrals when comparing pre- and post-implementation. The ferritin-guided donation interval researchers also noted that, “[i]n post-hoc sensitivity analyses, the odds of return for male repeat donors were significantly lower than for new male donors at 36–38 months, and in premenopausal and postmenopausal female donors, there were no significant differences in return of new or repeat donors…There were no consistent significant patterns for restless legs syndrome, pica, fatigue, cognitive functioning, mental and physical wellbeing, and warm glow after implementation of the new policy.”
The ferritin-guided donation interval paper’s authors concluded that, “[o]ur findings raise important policy and practical considerations [and] provide policy makers with a monitoring option that requires no effort from blood donors, could be more effective in protecting iron stores than standard h[e]moglobin monitoring practices, and does not impose a risk of side-effects compared with iron supplementation. However, the decreasing donor availability over time due to reduced odds of donor return, the risk of definite non-return after extended donation intervals, and increased numbers of deferred donors highlight the need for intensified donor recruitment and retention efforts.” Limitations of the study acknowledged by the researchers included, “[t]he nature of the intervention poses a risk of overestimating the positive effect of ferritin-guided donation intervals. Donors whose donation intervals are extended might return less frequently, introducing potential selection bias later in the study.”
Citation: Meulenbeld, A., Ramondt, S., Sweegers, M.G., et al. “Effectiveness of ferritin-guided donation intervals in whole-blood donors in the Netherlands (FIND’EM): a stepped-wedge cluster-randomised trial.” The Lancet. 2024.