MODULATION OF HEMATOPOIESIS BY KETANSERIN IN ERYTHROPOIETIN-TREATED UREMIC PATIENTS - EVIDENCE FROM PLATELET STUDIES

Recombinant human erythropoietin (EPO) not only ameliorates the anemia of renal failure but also modulates platelet function and corrects ur emic platelet serotonin (5-hydroxytryptamine, 5-HT) storage pool defic iency. We studied if ketanserin, a blocker of platelet and vascular sm ooth muscle receptors for 5-HT, could reverse any EPO-induced changes in hemostasis. A complete blood count, immunoreactive serum EPO concen tration, skin bleeding time (BT) and whole blood platelet aggregation (electric impedance method) induced by ristocetin and ADP, and intrapl atelet and whole blood 5-HT, were determined in seven chronic hemodial ysis (HD) patients before and after 1, 2, 4 and 8 weeks of EPO therapy , and repeated after a Lt-week co-treatment with oral ketanserin. Stim ulation of erythropoiesis was accompanied by a rise in the platelet co unt (P < 0.05), shortening of the BT (P < 0.02), an increase in platel et aggregability, and by replenished intraplatelet 5-HT store. Ketanse rin co-treatment produced an unexpected 33% fall in serum EPO level (P < 0.02), a decrease in the platelet count (P < 0.05), prolongation of the BT (P < 0.05) and depressed platelet aggregation in response to b oth agonists. There was no change in the amount of intraplatelet 5-HT while whole blood 5-HT concentration decreased significantly (P < 0.02 ). Strong positive correlations between the decrease in whole blood 5- HT and the prolongation of the BT (r = 0.786, P < 0.05), and between t he former parameter and the fall in the platelet count (r = 0.820, P < 0.05) were found. In conclusion, we report dual erythro-and thrombocy topoietic effects of EPO combined with correction of a platelet defect in the storage of 5-HT and enhanced platelet aggregability. The ketan serin-induced falls in serum EPO concentration and the platelet count provide new evidence of the dependency of thrombocytopoiesis on EPO in the initial weeks of the therapy. The 'antiplatelet' effects of ketan serin observed in this study seem to be due to reduction in circulatin g thrombocyte number rather than from any inhibitory effect on their a ggregation.