Anticoagulation in Mechanical Circulatory Support: Contemporary Challenges and Future Directions in Cardiovascular Pharmacotherapy.

Mechanical circulatory support (MCS) is increasingly used in patients with cardiogenic shock, advanced heart failure, and severe respiratory failure; however, anticoagulation management remains challenging due to the competing risks of thrombosis, bleeding, hemolysis, and device dysfunction. In this review, we synthesize contemporary evidence on anticoagulant selection, monitoring strategies, and device-specific management across major MCS platforms, including extracorporeal membrane oxygenation, temporary ventricular assist devices, Impella devices, and durable left ventricular assist devices. Unfractionated heparin remains the cornerstone anticoagulant across most MCS platforms, while anti-factor Xa-guided monitoring is increasingly incorporated into clinical practice in many centers alongside activated partial thromboplastin time and other monitoring modalities. Direct thrombin inhibitors represent important alternatives, particularly for patients with heparin-induced thrombocytopenia or heparin resistance. Recent advances include bicarbonate-based purge strategies for Impella support and evolving antithrombotic approaches in HeartMate 3 recipients, introduced by the ARIES-HM3 trial. Emerging investigational strategies, including direct oral anticoagulants, factor XI/XII inhibition, and precision anticoagulation approaches, show promise for improving hemocompatibility; however, current evidence remains limited, and further prospective studies are required before these strategies can be routinely adopted. Overall, contemporary evidence supports an individualized approach to anticoagulation based on device characteristics, patient-specific risk profiles, and current guideline recommendations, while highlighting important knowledge gaps that warrant further high-quality prospective investigation.