Global hypercoagulability in patients with schizophrenia receiving long-term antipsychotic therapy

Background: Patients with schizophrenia are at increased risk of venous thromboembolism. The mechanisms underlying this association are poorly understood. Aims: We investigated whether there is a global hypercoagulable state in patients with schizophrenia utilising the overall haemostatic potential (OHP) assay which assesses overall coagulation potential (OCP), haemostatic potential (OHP) and fibrinolytic potential (OFP). Method: Citrated plasma was collected for OHP assays from patients with schizophrenia on long-term antipsychotic treatment and compared with healthy age- and sex-matched controls. Time courses of fibrin formation and degradation were measured by spectrophotometry (absorption of 405. nm) after the addition of tissue factor and tissue plasminogen activator to plasma. Results: Ninety patients with schizophrenia (antipsychotic treatment-15.9 ± 9.7. years) and 30 controls were recruited. Patients with schizophrenia had higher rates of smoking and levels of inflammatory markers (high-sensitivity C-reactive protein and neutrophil-to-lymphocyte ratio) than controls. Whilst D-dimer, fibrinogen and platelet count did not differ between patients with schizophrenia and controls, the OCP (54.0 ± 12.6 vs 45.9 ± 9.1, p = 0.002) and OHP (12.6 ± 5.8 vs 7.2 ± 3.7, p < 0.001) were higher, and OFP was lower (76.6 ± 9.8% vs 84.9 ± 6.4%, p < 0.001) in patients with schizophrenia, implying both a hypercoagulable and hypofibrinolytic state in these patients. Importantly, abnormalities in overall coagulation were independently predicted by levels of plasminogen-activator-inhibitor-1, fibrinogen, platelet count, inflammatory markers and plasma triglycerides, suggesting a multifactorial aetiology. Conclusion: Patients with schizophrenia have evidence of a global hypercoagulable and hypofibrinolytic state which may contribute to their increased risk of venous thromboembolism.