title: Global hypercoagulability in patients with schizophrenia receiving long-term antipsychotic therapy.
abstract: BACKGROUND
  Patients with schizophrenia are at increased risk of venous thromboembolism. The mechanisms underlying this association are poorly understood.
  
  
  OBJECTIVE
  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).
  
  
  METHODS
  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 405nm) after the addition of tissue factor and tissue plasminogen activator to plasma.
  
  
  RESULTS
  Ninety patients with schizophrenia (antipsychotic treatment-15.9±9.7years) 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.
  
  
  CONCLUSIONS
  Patients with schizophrenia have evidence of a global hypercoagulable and hypofibrinolytic state which may contribute to their increased risk of venous thromboembolism.
authors: ANZAC Research Institute, Sydney, Australia; Department of Cardiology, Concord Repatriation General Hospital, Sydney Local Health District, Sydney, Australia; University of Sydney, Australia.
authors: Vincent
authors: V
authors: Chow
authors: ANZAC Research Institute, Sydney, Australia; Department of Cardiology, Concord Repatriation General Hospital, Sydney Local Health District, Sydney, Australia; University of Sydney, Australia.
authors: Caroline
authors: C
authors: Reddel
authors: ANZAC Research Institute, Sydney, Australia; Department of Cardiology, Concord Repatriation General Hospital, Sydney Local Health District, Sydney, Australia; University of Sydney, Australia.
authors: Gabrielle
authors: G
authors: Pennings
authors: Brain & Mind Research Institute, University of Sydney, Australia.
authors: Elizabeth
authors: E
authors: Scott
authors: Department of Psychiatry, Croydon Health Centre, Sydney, Australia.
authors: Tundra
authors: T
authors: Pasqualon
authors: Department of Cardiology, Concord Repatriation General Hospital, Sydney Local Health District, Sydney, Australia; University of Sydney, Australia.
authors: Austin C C
authors: AC
authors: Ng
authors: Department of Cardiology, Concord Repatriation General Hospital, Sydney Local Health District, Sydney, Australia.
authors: Thomas
authors: T
authors: Yeoh
authors: ANZAC Research Institute, Sydney, Australia; University of Sydney, Australia; Department of Haematology, Concord Repatriation General Hospital, Sydney Local Health District, Sydney, Australia.
authors: Jennifer
authors: J
authors: Curnow
authors: ANZAC Research Institute, Sydney, Australia; Department of Cardiology, Concord Repatriation General Hospital, Sydney Local Health District, Sydney, Australia; University of Sydney, Australia. Electronic address: leonard.kritharides@sydney.edu.au.
authors: Leonard
authors: L
authors: Kritharides
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology; D005260:Female; D005337:Fibrin / Q000378:metabolism; D006801:Humans; D008297:Male; D010949:Plasma / Q000187:drug effects / Q000378:metabolism; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy*; D013053:Spectrophotometry; D019851:Thrombophilia / Q000139:chemically induced / Q000503:physiopathology*; D013925:Thromboplastin / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; D005337:Fibrin; D013925:Thromboplastin; D010959:Tissue Plasminogen Activator
keywords: Blood coagulation test; Coagulation; Fibrinolysis; Schizophrenia; Thrombosis