Erythropoietin (EPO) therapy in hemodialysis patients may be associated with an enhanced risk of vascular access and extracorporeal thrombosis. Assessment of blood coagulation and fibrinolysis was performed monthly on a group of 21 hemodialysis patients treated with EPO, and on four iron-deficient hemodialysis patients treated with iron dextran infusions alone. Seventeen of the EPO treated patients were also monitored after withdrawal of EPO to allow hemoglobin to fall to pre-EPO levels, and 16 of these patients during a second subsequent phase of EPO therapy with EPO administered using the alternative route (subcutaneous/intravenous) from the first phase of treatment. Ten untreated hemodialysis patients with intrinsically high hemoglobins were studied as controls. EPO was associated with significant increases in the endothelial product Factor VIII von Willebrand factor antigen (FVIIIvWFAg), and plasma fibrinogen, to levels comparable to those observed in the untreated control patients. Both FVIIIvWFAg and fibrinogen remained significantly elevated when EPO was withdrawn. Whole blood platelet aggregation (spontaneous, collagen, and ADP-induced) also increased following EPO, collagen and ADP-induced aggregation, increasing further when EPO was withdrawn. Transient but significant changes occurred in plasma measures of thrombin-antithrombin III complex, prostacyclin stimulating factor, and protein C during the first EPO treatment phase, and also thrombin-antithrombin III complex during the second treatment phase, all favoring a tendency to thrombosis. D-dimer increased significantly following EPO withdrawal. Erythrocyte deformability, and granulocyte aggregation did not change. There was no effect of route of EPO administration (subcutaneous or intravenous) or EPO dose on any of these parameters.(ABSTRACT TRUNCATED AT 250 WORDS)