Atypical antipsychotic clozapine binds fibrinogen and affects fibrin formation

Abstract

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Clozapine‐induced pulmonary embolism in a patient with no pre‐existing risk factors: A case report

“…Clozapine has also been found to increase platelet adhesion and aggregation and reduce activated partial thromboplastin time (aPTT), 19 which can lead to the development of VTE. A recent in vitro study revealed that in a dose‐dependent manner, clozapine affects fibrin formation by reducing coagulation speed and fibrin fiber thickness, leading to fibrinogen acquiring increased thrombogenic properties 20 . Treatment with clozapine for a duration longer than 2½ years can lead to elevated serum concentrations of IgM antiphospholipid antibodies, which are, although rarely, associated with arterial and venous thrombosis 21 .…”

“…A recent in vitro study revealed that in a dose-dependent manner, clozapine affects fibrin formation by reducing coagulation speed and fibrin fiber thickness, leading to fibrinogen acquiring increased thrombogenic properties. 20 Treatment with clozapine for a duration longer than 2½ years can lead to elevated serum concentrations of IgM antiphospholipid antibodies, which are, although rarely, associated with arterial and venous thrombosis. 21 Our patient had commenced clozapine only 14 days prior, and while anti-phospholipid antibody levels were not evaluated in our patient, serum analysis showed a normal APTT (Table 1).…”

“…6 A growing number of studies have described an association between antipsychotic therapy, particularly clozapine, [7][8][9] and an increased risk of VTEs. [10][11][12][13][14][15][16] Several mechanisms have been proposed, such as venous stasis secondary to sedation and reduced mobility, 17,18 increased platelet adhesion and aggregation, 19,20 and elevated serum IgM antiphospholipid antibodies. 21 Despite this, current UK guidelines do not routinely recommend pharmacological VTE prophylaxis alongside antipsychotic treatment.…”

Clozapine: An Updated Overview of Pharmacogenetic Biomarkers, Risks, and Safety—Particularities in the Context of COVID-19

“…A recent in vitro study revealed that clozapine enhances the risk of developing thrombosis in patients on CLZ, by reducing coagulation time and fibrin fibers' thickness, developing a thrombogenic pattern in a dose-dependent manner [85].…”

Clozapine. Pharmacodynamic Mechanisms, Potential Pharmacogenetic Biomarkers, and Risks in Schizophrenia. Particularities in the Context of Covid-19. An Updated Overview

“…Another hematological side effect might be at the root of the venous thromboembolism in the patients treated with clozapine -the increases in adhesion and aggregation of blood platelets [78]. A recent in vitro study revealed that clozapine binding affected fibrin formation by reducing coagulation speed and thickness of fibrin fibers by fibrinogen developing thrombogenic characteristics, dose-dependent, increasing the risk for development thrombosis in patients on clozapine treatment [79]. Patients diagnosed with schizophrenia are at higher risk of obesity and cardiovascular diseases; this observation being another pathophysiological explanation of the increased risk of pulmonary embolism [80] but also of aspiration pneumonia [81].…”