Factor XIII (FXIII) contributes to clot stability and reduces clot susceptibility to lysis through fibrin cross-linking. Standard coagulation tests like prothrombin time and activated partial thromboplastin time do not assess FXIII activity and therefore cannot detect FXIII deficiency. Acquired FXIII deficiency has been reported in bleeding patients in trauma and perioperative settings, although a causal relationship has not been established [1]. Recent European guidelines suggested monitoring FXIII and correcting deficiencies, despite low-quality evidence supporting this practice [2]. Acquired FXIII deficiency has also been reported in patients on extracorporeal membrane oxygenation (ECMO), but data remain limited [3]. Moreover, the time-weighted average (TWA) of FXIII levels, reflecting cumulative exposure to deficiency, has never been investigated. We aimed to evaluate TWA FXIII plasma levels during veno-arterial (VA)-ECMO support. We hypothesized that VA-ECMO would be associated with meaningful cumulative exposure to acquired FXIII deficiency.