Biomarkers of thrombotic tendency in schizophrenia and related psychoses: Implications for the potential usefulness of anticoagulants in schizophrenia

Many published studies report that antipsychotic therapy is associated with thrombotic tendency. However, fewer studies have examined whether thrombotic tendency exists in unmedicated schizophrenia (SZ) or other psychoses. In addition, some studies have reported a full remission of psychotic symptoms with warfarin, a well-known anticoagulant, raising the possibility that psychosis may be associated with thrombotic tendency. Here, we summarize the available literature on biomarkers of thrombotic tendency in unmedicated patients with SZ and other psychoses. A PubMed search using the keywords "psychosis" OR "schizophrenia" AND ("coagulation" OR "tissue plasminogen activator" OR "thromboembolism") for studies published between 2012 and 2023 yielded 290 results. Inclusion criteria were 1) controlled studies, 2) studies including patients with psychosis, 3) English language. Exclusion criteria included 1) review articles, 2) case reports, 3) focus on antipsychotics as a factor in thrombotic tendency. Seven studies met criteria and were included for qualitative synthesis in this review. Five studies included patients with SZ and related psychoses, while two studies also included patients with major depression and bipolar disorders. Numerous plasma proteins involved in regulating coagulation were identified as being low in patients with SZ, including fibrinolytic enzymes such as tissue-type plasminogen activator (tPA), plasmin, protein S, and plasminogen, although one study found that tPA was reduced in chronic SZ but elevated in first-episode SZ (FES) patients. Those reports suggestive of thrombotic tendency in schizophrenia and related psychoses warrant further investigation, especially in drug-naïve first episode samples as compared to chronic patients, where antipsychotic treatment may contribute to thrombotic tendency. If confirmed, therapeutic strategies with anticoagulants like tPA may represent a novel approach to managing schizophrenia.