EFFECTS OF LONG-TERM TREATMENT WITH RECOMBINANT-HUMAN-ERYTHROPOIETIN ON PHYSIOLOGICAL INHIBITORS OF COAGULATION

Recombinant human erythropoietin (rHu-EPO) in the treatment of renal a nemia might predispose to an increased risk of thrombotic complication s. In an attempt to comprehend the involvement of the physiologic inhi bitors of coagulation in this process, we studied 2 groups of hemodial ysis patients. Group I included 21 patients receiving a starting dose of 90 IU/kg/week s.c., and group II included 17 patients without rHu-E PO. The following coagulation tests were performed before rHu-EPO trea tment, and after 1, 6 and 12 months: prothrombin time; activated parti al fistula thromboplastin time; fibrinogen; plasminogen activity; anti thrombin III activity; protein C activity; total and free protein S an tigens, and C4b binding protein. Only the latter three parameters were changed in group I, while high baseline levels of protein S antigens were found in both groups. A decrease in total and free protein S was observed within 1 month of treatment. At the 6th month total protein S returned to near pretreatment values, whereas a significant fall in f ree protein S (p = 0.007) was observed. All three parameters returned to near baseline values by 12 months. These results suggest that prote in S activity can be altered at the beginning of EPO therapy, a change that under favoring circumstances might contribute to the thrombotic events reported during the early phase of rHu-EPO treatment.