title: Efficacy of iloprost (ZK36374) versus aspirin in preventing heparin-induced platelet activation during cardiac operations.
abstract: For patients with heparin-induced platelet activation, reexposure to heparin can result in profound thrombocytopenia, intravascular thrombosis, and hemorrhage. We compared the ability of aspirin to that of iloprost (ZK36374), an analogue of prostacyclin, in preventing heparin-induced platelet activation and thus permitting a cardiac operation in a patient with heparin-induced platelet activation. Despite abolishing thromboxane A2 synthesis, aspirin (4 mmol/L) failed to prevent either in vitro heparin-induced platelet aggregation (65.0% without versus 59% with aspirin) or carbon 14-serotonin release (81.8% without versus 59.7% with aspirin). In contrast, iloprost (0.01 mumol/L) prevented both in vitro heparin-induced platelet aggregation (65% without versus 5.0% with iloprost) and release (81.8% without versus 0% with iloprost). Consequently, a continuous infusion of iloprost was begun before administration of heparin, continued throughout cardiopulmonary bypass, and discontinued 15 minutes after administration of protamine. The whole blood platelet count (209,000/microliter) remained stable after intraoperative administration of heparin (238,000/microliter) and was 115,000/microliter after the operation. No spontaneous platelet aggregates were observed in samples of platelet-rich plasma after heparin administration, and no platelet transfusions were required. Plasma levels of platelet factor 4 rose from 27 to 725 ng/ml after heparin administration but then declined during bypass to 50 ng/ml. Beta thromboglobulin levels only rose from 92 to 496 ng/ml with administration of heparin. Fibrinopeptide A levels fell from 72 to 22 ng/ml after heparin and remained stable throughout bypass. The template bleeding time was 7.5 minutes preoperatively and 8.0 minutes postoperatively. The postoperative chest tube drainage (12 hours) was 475 ml, and platelets responded normally to adenosine diphosphate. In conclusion, iloprost but not aspirin completely prevented heparin-induced platelet activation in vitro. Furthermore, iloprost effectively prevented this syndrome clinically, which permitted a safe cardiac operation in this patient with heparin-induced platelet activation.
mesh_terms: D000368:Aged; D001241:Aspirin / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects*; D006348:Cardiac Surgical Procedures / Q000379:methods*; D011464:Epoprostenol / Q000627:therapeutic use*; D005260:Female; D006494:Heparin Antagonists / Q000627:therapeutic use*; D006801:Humans; D016285:Iloprost
chemical_list: D006494:Heparin Antagonists; D011464:Epoprostenol; D016285:Iloprost; D001241:Aspirin