INFLUENCE OF RECOMBINANT-HUMAN-ERYTHROPOIETIN ON PLATELET-FUNCTION AND COAGULATION-FACTORS

Reports on the effect of recombinant human erythropoietin (r-HUEPO) on the platelet activity are conflicting. In the present study platelet function and coagulation factors were investigated in 20 patients with end-stage renal failure on maintenance hemodialysis. The patients wer e randomized into two groups and, in a crossover design, investigated during intravenous and subcutaneous administration of rHUEPO. The two groups started with a different administration form (intravenously in group 1 and subcutaneously in group 2), and each mode of treatment was given for 3 months. At entrance into the study the platelets were hyp eraggregable to exogenous stimulation with collagen (COL) in both grou ps. Group 1 developed increasing platelet sensitivity to adenosine dip hosphate (ADP; 0.01 < p < 0.025) during intravenous treatment. Concomi tantly, three episodes of arteriovenous fistula thrombosis occurred. I n group 2 one event of fistula thrombosis occurred despite there being no change in platelet reactivity to ADP. After 3 months on r-HUEPO, t he platelet reactivity to ADP decreased significantly in both groups, but also the reactivity to COL declined significantly: 0.01 < p < 0.02 5 (group 1) versus 0.001 < p < 0.005 (group 2). The platelet reactivit y to ristocetin remained unchanged in group 1, but decreased significa ntly in group 2. In group 1 fibrinogen was increased significantly (0. 001 < p < 0.005) at the time of the clotting events. The factor VIII:c oagulant activity increased, but antithrombin III, activated factors X and XIII, activated protein C, activated thromboplastin time, and par tial prothrombin time remained unchanged. Furthermore, 4 patients in g roup 1 and 2 patients in group 2 required an increased dose of heparin after 2-3 months of investigation. Thus, r-HUEPO seemed to influence platelet function. Enhanced activity was observed during intravenous a dministration. Eventually, platelet reactivity to ex vivo stimulation decreased in both groups. Thus, intravascular hemostatic activation se emed to occur following r-HUEPO administration. An increase in hematoc rit is probably of importance, but according to the present data, tran sient platelet activation may also be a contributory factor.