Effects of erythropoietin on platelet reactivity and thrombopoiesis in humans

A recent study in dogs suggested that erythropoietin (EPO) not only promote s the synthesis of increased numbers of reticulated platelets but that thes e newly produced platelets are hyperreactive compared with controls, Becaus e of the increasing use of EPO in the perioperative setting, we characteriz ed the effects of EPO on platelet reactivity in healthy human volunteers. I n a randomized, controlled trial, we studied the effects of EPO on platelet reactivity, thrombopoiesis, and endothelial activation in circumstances si milar to those of autologous blood donation. Thirty healthy male volunteers received placebo or EPO (100 or 500 U/kg of body weight given intravenousl y) three times a week for 2 weeks and underwent phlebotomy on days 8 and 15 , Thrombin receptor-activating peptide induced expression of P-selectin, an d CD63 increased 2- to 3-fold during EPO treatment. The enhanced platelet r eactivity was also reflected by a 50% increase in soluble P-selectin in pla sma. Plasma E-selectin levels increased in a dose-dependent fashion by more than 100% during EPO treatment, indicating substantial activation of endot helial cells. A 10% to 20% increase in platelet counts was observed in both EPO groups on day 5, In the placebo group, platelets increased only severa l days after the first phlebotomy, The increase in platelet counts was not reflected by changes in the amounts of reticulated platelets or circulating progenitor cells. In summary, we found that EPO markedly enhances endothel ial activation and platelet reactivity, which may adversely affect patients at cardiovascular risk. However, the increased platelet reactivity could b e exploited in patients with platelet dysfunction. (Blood, 2000;95:2983-298 9) (C) 2000 by The American Society of Hematology.