clozapine and Thrombophilia

An increasing number of reports suggest a link between venous thromboembolism (VTE) and the use of antipsychotics. To better understand this association the available body of evidence has been critically scrutinised. Relevant articles were identified in the databases Scopus and PubMed. Several observational studies using different methodologies show an increased risk of VTE in psychiatric patients. This elevated risk seems to be related to the use of antipsychotic medication and in particular to the use of clozapine and low-potency first-generation drugs. Many studies investigating the association have, however, methodological limitations. The biological mechanisms involved in the pathogenesis of this possible adverse reaction are largely unknown but several hypotheses have been suggested such as drug-induced sedation, obesity, increased levels of antiphospholipid antibodies, enhanced platelet aggregation, hyperhomocysteinemia and hyperprolactinemia. The association may also be related to underlying risk factors present in psychotic patients. Physicians need to be aware of this possible adverse drug reaction. Although supporting evidence has not been published they should consider discontinuing or switching the antipsychotic treatment in patients experiencing VTE. In addition, although data is lacking, the threshold for considering prophylactic antithrombotic treatment should be low when risk situations for VTE arise, such as immobilisation, surgery and so on.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Case-Control Studies; Catatonia; Clozapine; Death, Sudden; Dehydration; Female; Humans; Male; Middle Aged; Models, Biological; Platelet Aggregation; Pulmonary Embolism; Restraint, Physical; Retrospective Studies; Risk; Risk Factors; Thrombophilia; Venous Thromboembolism; Young Adult

Clozapine treatment for resistant schizophrenic disorders has been associated to venous thromboembolic events. We report the case of a patient who developed upper-extremity deep vein thrombosis just 2 months after starting on clozapine in whom the thrombophilia work-up revealed the presence of the prothrombin G20210A mutation.

Topics: Clozapine; Humans; Male; Middle Aged; Point Mutation; Prothrombin; Thrombophilia; Upper Extremity; Venous Thrombosis

Clinical studies suggest that the second generation antipsychotics (APs) clozapine and olanzapine and to a lesser extent the typical antipsychotics may be associated with a procoagulant and proinflammatory state that promotes venous thromboembolism. We evaluated here several blood factors associated with coagulation and inflammation in AP-treated schizophrenia patients and their first-degree relatives.. Procoagulant factors (fibrinogen and plasminogen activator inhibitor [PAI-1]), the anticoagulant factor antithrombin III [AT-III], and inflammation-related factors (C-reactive protein [CRP] and leptin) were assessed in patients chronically treated with clozapine (n=29), olanzapine (n=29), typical APs (n=30) and first degree relatives of clozapine (n=23) and olanzapine subjects (n=11).. The typical AP group had the highest CRP level (p=0.013) in spite of having the lowest body mass index (BMI). Patients as a single group had higher CRP levels than relatives (p=0.003). The typical AP group also had the highest AT-III levels (p=0.021). Fibrinogen levels did not differ between the groups (p=0.13). Olanzapine patients displayed the highest PAI-1 and leptin levels among the drug-treated subjects, but values were similar to those observed in their relatives, and were significantly correlated with the BMI.. A homogeneous negative profile of high inflammation and procoagulant factors along with low levels of anticoagulants was not detected in any group. While preliminary, our results suggest that the observed abnormalities were not related to a direct drug effect, but to elevated BMI (high PAI-1 and leptin in olanzapine-treated patients). We speculate that the high CRP in the typical AP group might be related to poor lifestyle habits, but this must we confirmed in future studies.

Topics: Adult; Antipsychotic Agents; Antithrombin III; Benzodiazepines; Body Mass Index; C-Reactive Protein; Clozapine; Dose-Response Relationship, Drug; Female; Fibrinogen; Humans; Inflammation Mediators; Leptin; Life Style; Male; Middle Aged; Olanzapine; Plasminogen Activator Inhibitor 1; Risk Factors; Schizophrenia; Thromboembolism; Thrombophilia

Topics: Adult; Antipsychotic Agents; Clozapine; Female; Hallucinations; Humans; Thrombophilia