Characterizing the Thrombotic Spectrum and Clinical Phenotypes of Tranexamic Acid-Associated Adverse Events: A...

Tranexamic acid (TXA) is widely used to reduce bleeding in surgical, trauma, obstetric, and gynecological settings. However, concerns remain regarding TXA-associated thrombotic adverse events, and their phenotypic heterogeneity and clinical severity have not been comprehensively characterized. This study investigated TXA-associated thrombotic events using the Food and Drug Administration Adverse Event Reporting System (FAERS) from 2004Q1 to 2026Q1. Thrombotic adverse events were identified using the Standardized MedDRA Query (SMQ) "Embolic and thrombotic events" and evaluated by disproportionality analysis based on reporting odds ratios (RORs). Qualifying thrombotic events were assigned to the SMQ vessel-type subgroups-arterial, vessel-type unspecified/mixed, and venous-and demographic characteristics, indications, clinical outcomes and time-to-onset were compared across subgroups; signal strength was further related to clinical severity. In all, 515 thrombotic cases associated with TXA and 26 selected thrombotic terms were found (arterial, 157; mixed, 168; venous, 190). Venous thromboembolism-pulmonary embolism (n = 128, ROR 13.94) and deep vein thrombosis (n = 58, ROR 9.09)-is the most frequent type and brings about the most severe and fatal consequences (death reported in 16.8% of venous versus 2.5% of arterial reports), whereas the strongest disproportionality signals were observed for rare site-specific events such as ovarian vein thrombosis (ROR 352.95) and cerebral venous sinus thrombosis (ROR 118.35). The three subgroups differed markedly in demographic and clinical characteristics: venous events occurred predominantly in women (73.7%) treated for menorrhagia (35.3%), whereas arterial events arose mainly in surgical or procedural settings (intravenous route 36.3%; surgery/prophylaxis 19.1%) and presented earliest after exposure [median time-to-onset (TTO) 0 versus 7 days]. Signal strength was not concordant with clinical severity across the thrombotic spectrum. These findings provide a deeper understanding of the thrombotic safety of TXA, indicate that the clinical background may influence the phenotypic differences among the different thrombotic types, and emphasize the necessity of enhanced attention and risk stratification in high-risk groups.