Background Extracorporeal membrane oxygenation (ECMO) induces hemostatic alterations that may contribute to hematological complications. Unfractionated heparin (UFH) is the mainstay antithrombotic in ECMO and depends on antithrombin III (AT III) to exhibit its actions. However, it bears the risk for heparin‐induced thrombocytopenia. Bivalirudin is a direct thrombin inhibitor and is inherently not dependent on AT III. Aim of the Study To assess the efficacy and safety profiles of UFH compared with bivalirudin during ECMO support. Methods We retrospectively reviewed 52 adult patients who were supported by ECMO from 1 January 2013 to 1 September 2018. Among them, 33 received UFH and 19 received bivalirudin. We analyzed their 7‐day rate of composite thrombotic, bleeding, and mortality episodes while on anticoagulation. Results There were no statistical differences in the 7‐day rate of composite thrombosis (33.3% vs 26.3%; P = 0.60), major bleeding (18.2% vs 5.3%; P = .24), 30‐day mortality, (42.4% vs 26.3%; P = .37), or in‐hospital mortality (45.5% vs 36.8%; P = .58). The percentage of time activated partial thromboplastin time (aPTT) was within the therapeutic range was higher with bivalirudin (50% vs 85.7%; P = .007). Conclusions This study suggests that UFH and bivalirudin are associated with similar rates of thrombosis, major bleeding, and mortality events in patients supported by ECMO. However, it was observed that bivalirudin consistently maintained aPTT within the therapeutic range in comparison to UFH.

A 48-year-old male patient requiring extracorporeal membrane oxygenation (ECMO) support for hypoxaemic respiratory failure failed to achieve therapeutic anticoagulation with bivalirudin after continuous dose escalations, and continued to have recurrent fibrin stranding in the circuit over a 6-day course of treatment. Suspecting bivalirudin resistance, the patient was transitioned to argatroban and achieved a therapeutic response in less than 24 hours. The case describes the challenges of anticoagulation in ECMO supported patients. The interplay between bivalirudin metabolism, renal replacement therapy, and immunological effects leading to a heparin-like-effect, inflammatory mediators, and thrombotic burdens may all impact the clinical effect during bivalirudin therapy. The structural biochemistry of thrombin and bivalirudin likely plays a role in the presented patient’s successful response to argatroban. Bivalirudin may fail at achieving therapeutic anticoagulation in patients with genetic thrombin mutations or structural defects that alter the binding pockets at the thrombin exosites.