Evidence Of Relative Iron Deficiency in Apheresis Platelet Donors Correlates With Donation Frequency
Authors: Condon Frances , Li Huihui , Kessler Debra , Nandi Vijay , Ganz Tomas , Nemeth Elizabeta , Westerman Mark , Shaz Beth H , Ginzburg Yelena 
Published: October 2019

Abstract
A minimal hemoglobin (Hb) of 12.5 g/dL is required to protect blood donors from iron-deficiency and anemia and ensure collection of an adequate red cell product. The effects of whole blood or red blood cell (RBC) donation on donor Hb concentration and iron stores have been extensively studied. These changes have not been well characterized in platelet donors. Because platelet donation can occur as frequently as every 72 hours up to 24 times per year, tubes taken for donor testing (approximately 50 mL) at each donation may result in the loss of blood volume equivalent to 2-3 units of whole blood (500 mL each) in frequent donors. We hypothesized that iron deficiency and its associated thrombocytosis is underappreciated in platelet donors.
To test this hypothesis, we proposed to 1) analyze the degree of iron deficiency / depletion in platelet donors, 2) assess the correlation between pre-donation platelet count with iron stores, and 3) evaluate the effect of platelet donation frequency on erythropoiesis- and iron-related parameters in white males age 40-65 years, typically representative of the platelet donor pool. Eligible donors were selected from a donor pool who had not donated whole blood / RBCs in the previous 12 months prior to study enrollment. Prospective participants with a history of iron-related pathology (e.g. iron deficiency, hereditary hemochromatosis, anemia, bleeding, or abnormal colonoscopy findings) were excluded from the study. Eligible donors who had not donated any blood products in the prior 12 months were enrolled as controls. Analysis of circulating RBC parameters, serum iron, serum ferritin, serum transferrin concentration and saturation, serum hepcidin, and soluble serum TfR1 were performed and correlations analyzed. The “TfR1 Ferritin Index” (i.e. log(sTfR1/ferritin)) was also evaluated, representing iron restricted erythropoiesis in the absence of frank iron deficiency. Statistical significance was measured using a student t-test; data is presented as mean ± s.e.m. and p<0.05 was considered statistically significant.
Fifty eligible platelet donors and eight controls were enrolled in the study. Average age of platelet donors was 56±1 years, no different from that of controls (54±2 years; p=0.6). More donors (22/50 (44%)) were taking multivitamins compared to controls (2/8 (25%)). Only a small number of platelet donors (2/50 (4%)) had previously been deferred for low Hb. Although within the normal range, platelet donors were found to have a lower serum ferritin (54±6 vs.169±60 ng/mL; p<0.0001), transferrin saturation (30±1 vs. 40±7%; p=0.04), and serum hepcidin (35±3 vs. 57±11 mg/mL; p=0.006) relative to controls. In addition, TfR1 ferritin index was suggestive of relatively iron restricted erythropoiesis in platelet donors relative to controls (p=0.005). These results support our premise that platelet donors are relatively more iron deficient. Furthermore, among donors, lower MCV (89±1 vs. 93±1 fL; p=0.03) and CHr (31±0.4 vs. 32±0.4 pg; p=0.03) were observed in those who had donated platelets more than ten times relative to those who had donated once or twice. Lower hepcidin concentration (24±3 vs. 48±6 mg/mL, p=0.005), serum ferritin (38±7 vs. 77±16 ng/mL; p=0.04), and hepcidin/log ferritin (16.0±1.6 vs. 27.0±3.4, p=0.01) were observed in those who had donated platelets more than ten donations relative to those who had donated once or twice. Correlations between hepcidin and donation frequency (r=-0.396), serum ferritin and donation frequency (r=-0.323), and confirmatory hepcidin and log ferritin (r=0.454) were noted in platelet donors. Lastly, pre-donation platelet count correlated with sTfR1 (r=0.418), suggesting that thrombocytopoiesis is stimulated in the setting of relative iron restricted erythropoiesis.
Taken together, this pilot study for the first time demonstrates evidence of iron restricted erythropoiesis in frequent apheresis platelet donors. An analysis of iron- and erythropoiesis-related parameters in a broader population of frequent platelet donors (i.e. male and female, white and non-white donors) may demonstrate a potential utility of iron replacement.

Disclosures:
Ganz: Intrinsic LifeSciences: Equity Ownership, Membership on an entity’s Board of Directors or advisory committees. Nemeth:Intrinsic LifeSciences: Equity Ownership, Membership on an entity’s Board of Directors or advisory committees. Westerman:Intrinsic LifeSciences: Employment, Equity Ownership, Membership on an entity’s Board of Directors or advisory committees.