Prevention of heparin-induced thrombocytopenia during open heart surgery with iloprost (ZK36374).

Recurrent thrombocytopenia, thrombosis, or sudden death may develop in patients with heparin-induced thrombocytopenia who are reexposed to heparin. Three patients came to us in whom a diagnosis of heparin-induced thrombocytopenia had been made on the basis of ctinicat and serologic evidence; these patients required reexposure to heparin because of urgent cardiac surgery. Therefore, we evaluated the ability of iloprost (ZK36374), a new analogue of prostacycltn, to prevent heparin-dependent activation of platelets and thereby permit obligatory heparinization for safe extracorporeal circulation. Before operation, we demonstrated that iloprost prevented both heparin-dependent platelet aggregation and tritiated rH) -serotonin release in vitro. Therefore a continuous in&ion of iloprost was begun 1 hour before heparinization and was continued throughout cardt’opulmonary bypass and for an additional 75 minutes after protamine administration. The mean platelet count of 130,000/~1 before operation remained stable, and no spontaneous platelet aggregation was observed in samples of platelet-rich plasma obtained before cardiopulmonary bypass but after heparin administration. Similarly, after heparin administration but bejore bypass, platelet responsiveness to adenosine diphosphate remained unchanged when compared with preoperative values. Plasma levels of platelet factor 4 increased from 26 f 1 rig/ml (5E + standard error) to 843 + 383 rig/ml after heparin administration but actually decreased throughout cardiopulmonary bypass to 52 + 25 rig/ml. P-thromboglobult’n levels increased from 103 f 16 to 244 + 94 rig/ml with heparinization. The mean bleeding time was 10.5 minutes preoperatively and 13.3 minutes postoperatively. The mean amount of postoperative chest tube drainage (duration: 12 hours) was 432 k 67 ml. Thus, despite the conjirmed presence of heparin-dependent platelet-activating factor in the plasma of these three patients, iloprost prevented heparin-induced platelet activation during cardiopulmonary bypass while preserving platelet junction, as would be desired for postoperative hemostasis.