Hepcidin in Male Double Red Blood Cell Donors - Relationship Between Parameters of Iron Metabolism and Erythropoiesis

Abstract 2109

Hemoglobin (Hb) below 12.5g/dL accounts for more than 40% of all blood donor deferrals, and no standardized message is provided to these deferred donors. Furthermore, many donors who meet Hb standards are iron depleted. In light of this, the FDA requested comments on possibly changing the minimal acceptable Hb and/or the inter-donation interval. Here we explore several parameters of iron utilization after red blood cell (RBC) donation to understand its relationship to erythropoiesis.

Hepcidin is the central regulator of iron absorption, suppressed by low iron stores. We hypothesize that hepcidin values would identify donors with normal Hb levels and low iron stores and thus identify those who would benefit from iron replacement to prevent future low Hb deferral.

We enrolled eligible repeat male double RBC donors randomized to receive placebo (n=5) or iron supplementation (n=5) using 90 mg of elemental iron (feosol caplets). Donors were enrolled on day of donation and were invited to return at 2–4 day intervals during the 14 days following donation to compare with pre-donation markers of erythropoiesis and iron metabolism. In addition, buffy coats were collected on day 0 and again 7–10 days following donation (n=6) to quantify by flow cytometry circulating CD34+ cells as well as numbers of common myeloid progenitors (CMPs) and megakaryocyte erythroid progenitors (MEPs) in study donors.

Comparing iron supplemented to placebo receiving volunteers, ferritin was higher at 14 days in iron supplemented donors (18.6±3.9 vs 12.0±1.6 ng/mL) and corresponds with 52% vs. 36% of levels prior to donation relative to placebo (P=0.05). Furthermore, serum hepcidin nadirs earlier and rebounds sooner relative to placebo (15.4±3.2 vs. 6.8±2.1 ng/mL, P=0.05). Serum iron (150±37.1 vs. 60±5.8 mg/dL, P=0.04) and transferrin saturation (39.8±9.8 vs. 16.2±2.1%, P=0.05) are also increased relative to placebo by day 10 following donation. Although we found no difference in recovery of RBC count, hemoglobin, or hematocrit following donation, a trend toward a more sustained elevation in reticulocyte count is present relative to placebo (158±12.1 vs. 118±17.3 × 10⁹ cells/mL, P=0.07). CD34+ cells in circulation are increased following donation in all donors. Furthermore, only donors with baseline ferritin levels >20 ng/mL increased MEPs following donation. These later findings are consistent with expectations of iron regulatory mechanisms influencing erythropoiesis.

Taken together, these data suggest that a complex interplay between iron regulatory and erythropoietic mechanisms occurs during recovery from blood donation. Although it is currently unclear how iron regulation affects erythropoiesis, a larger (double) sample size will aid in the generation of criteria for donor iron supplementation.