norclozapine and Venous-Thrombosis

1. Several studies suggest an association between venous thromboembolism and the use of antipsychotic drugs, especially clozapine, but the biological mechanisms are unknown. It has been suggested that antipsychotic drugs enhance aggregation of platelets and thereby increase the risk of venous thrombosis. The purpose of the present study was to examine the effects of clozapine and its main metabolite, N-desmethyl clozapine, as well as olanzapine, risperidone and haloperidol, on platelet adhesion and aggregation and on plasma coagulation in vitro. 2. Blood was collected from healthy subjects free of medication. Platelet adhesion to different protein surfaces and aggregation were measured in microplates. The coagulation methods of activated partial thromboplastin time (APTT) and prothrombin time were performed in platelet-poor plasma. 3. Clozapine was the only compound that increased platelet adhesion and aggregation and shortened APTT. The effect appeared at therapeutic concentrations and was significant but weak. 4. This weak effect of clozapine on haemostasis may explain, in part, the association of this compound and venous thromboembolism.

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Blood Coagulation; Blood Platelets; Clozapine; Dose-Response Relationship, Drug; Female; Haloperidol; Humans; In Vitro Techniques; Male; Middle Aged; Olanzapine; Partial Thromboplastin Time; Platelet Adhesiveness; Platelet Aggregation; Prothrombin Time; Risperidone; Thromboembolism; Venous Thrombosis