The Donation Interval of 56 Days Requires Extension to 180 Days for Whole Blood Donors to Recover from Disturbances in Iron Homeostasis
Authors: N.Schotten Nienke , Pasker-de Jong Pieternel C , Moretti Diego , Zimmermann Michael Bruce , Kraaij Marian G , Swinkels Dorine W. 
Published: October 2019

Abstract
Background: To protect whole blood donors from developing iron deficiency and anemia, many blood banks require a minimum interval of 56 days between two donations. We aimed to assess whether the donation interval of 56 days is adequate in both new and regular donors to recover from changes in iron homeostasis.
Methods: Fifty male whole blood donors (25 new and 25 regular donors), were followed for 180 days after donating 500 mL of blood. Recovery of Hb and iron parameters (Hb, mean corpuscular volume (MCV), mean corpuscular Hb (MCH), MCH concentration (MCHC), red cell distribution width (RDW), reticulocytes, reticulocyte Hb content (CHr), iron, total iron-binding capacity (TIBC), transferrin saturation (TSAT), ferritin, soluble transferrin receptor (sTfR), sTfR-F index (sTfR/log ferritin), erythropoietin (EPO) and hepcidin) was investigated and tested for differences between new and regular donors in blood drawn at baseline (before donation) and at nine time points after blood donation. Differences in iron absorption and erythrocyte iron incorporation between new and regular donors were investigated with stable iron isotopes, administered at day 8 and measured at day 29.
Results: At baseline, levels of Hb and iron parameters differed between new and regular donors. In regular donors, Hb, ferritin and hepcidin were lower and EPO was higher compared to new donors. However, patterns of change in parameters over time after whole blood donation were similar for new and regular donors with an increase in EPO and decrease in Hb and hepcidin after day 2 followed by a decrease in ferritin and increase in reticulocytes, sTfR and TIBC after day 4. At day 57, only for TIBC all (100%) regular donors were back at pre-donation level (Figure 1). Percentages for other parameters ranged from 16.0% (regular donors) and 20.8% (new donors) for ferritin to above 80.0% for MCV, reticulocytes, CHr, hepcidin and ZPP (regular donors) and Hb, MCH, MCHC, reticulocytes, CHr, iron, TIBC, hepcidin and ZPP (new donors). At day 85 and 180, >90% of donors were back at their pre-donation levels for all parameters except for i) RDW, EPO, in both donor groups and ii) ferritin at day 85 in new (26.1%), and regular donors (48.0%) and at day 180 in new donors (78.3%). Importantly, for ferritin, when compared to regular donors, the increase in the percentage of new donors that reached pre-donation levels was slower over time and lower at 180 days. Iron absorption (17.0 and 21.9%, respectively) and incorporation into erythrocytes (81.6 and 83.7%, respectively) were not statistically significantly different between new and regular donors, but appeared to be higher in regular donors.
Conclusion: For the majority of blood donors the current interval of 56 days is too short to fully recover from a change in Hb and iron parameters after blood donation. Regular donation results in lower ferritin levels at baseline compared to new donors. Our data suggest that ferritin is a promising candidate parameter to personalize donation intervals. Moreover, they imply that prolongation of the donation interval from 56 to 180 days would i) prevent a further decrease of ferritin levels of regular donors, and ii) reduce the risk for iron deficiency associated symptoms upon subsequent donations.
Figure 1. Percentage of donors back at baseline levels (before blood donation) at day 57, 85 and 180 after blood donation. Solid lines: regular donors; dashed lines, new donors. Figure 1. Percentage of donors back at baseline levels (before blood donation) at day 57, 85 and 180 after blood donation. Solid lines: regular donors; dashed lines, new donors.

Disclosures
No relevant conflicts of interest to declare.