Antithrombotics and new interventions for venous thromboembolism: Exploring possibilities beyond factor IIa and factor Xa inhibition.

Abstract

Direct oral anti-activated factor X and antithrombin agents have largely replaced vitamin K antagonists as the standard of care in treatment of venous thromboembolism. However, gaps in efficacy and safety persist, notably in end-stage renal disease, implantable heart valves or assist devices, extracorporeal support of the circulation, and antiphospholipid syndrome. Inhibition of coagulation factor XI (FXI) emerges as a promising new therapeutic target. Antisense oligonucleotides offer potential advantages as a prophylactic or therapeutic modality, with one dose-finding trial in orthopedic surgery already published. In addition, monoclonal antibodies blocking activation and/or activity of activated factor XI are investigated, as are small-molecule inhibitors with rapid offset of action. Further potential targets include upstream components of the contact pathway such as factor XII, polyphosphates, or kallikrein. Finally, catheter-directed, pharmacomechanical antithrombotic strategies have been developed for high- and intermediate-risk pulmonary embolism, and large randomized trials aiming to validate their efficacy, safety, and prognostic impact are about to start.

• Authors: Anna C Mavromanoli, Stefano Barco, Stavros V Konstantinides
• Journal: Research and practice in thrombosis and haemostasis (Res Pract Thromb Haemost) Vol. 5 Issue 4 (May 2021) ISSN: 2475-0379 [Electronic] United States
• PMID: 34027284 (Publication Type: Journal Article)
• Copyright: © 2021 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).