In vitro effects of antipsychotics on human platelet adhesion and aggregation and plasma coagulation.
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.
Axelsson
Stina
S
Division of Pharmacology, Department of Medicine and Care, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
Hägg
Staffan
S
Eriksson
Andreas C
AC
Lindahl
Tomas L
TL
Whiss
Per A
PA
D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects*; D001792:Blood Platelets / Q000187:drug effects*; D003024:Clozapine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D010314:Partial Thromboplastin Time; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects*; D011517:Prothrombin Time; D018967:Risperidone / Q000494:pharmacology; D013923:Thromboembolism / Q000097:blood / Q000139:chemically induced; D020246:Venous Thrombosis / Q000097:blood / Q000139:chemically induced
D014150:Antipsychotic Agents; D001569:Benzodiazepines; C058272:norclozapine; D003024:Clozapine; D006220:Haloperidol; D018967:Risperidone; D000077152:Olanzapine