Thromb Haemost
DOI: 10.1055/s-0040-1716750
Invited Editorial Focus

Noncanonical Effects of Oral Thrombin and Factor Xa Inhibitors in Platelet Activation and Arterial Thrombosis

Amin Polzin*
1  Department of Cardiology, Pulmonology, and Vascular Medicine, Cardiovascular Research Institute Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf, Düsseldorf, Germany
,
Lisa Dannenberg*
1  Department of Cardiology, Pulmonology, and Vascular Medicine, Cardiovascular Research Institute Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf, Düsseldorf, Germany
,
Manuela Thienel
2  Department of Cardiology, LMU München, Munich, Germany
3  DZHK (German Centre for Cardiovascular Research), Munich Heart Alliance, Munich, Germany
,
Martin Orban
2  Department of Cardiology, LMU München, Munich, Germany
3  DZHK (German Centre for Cardiovascular Research), Munich Heart Alliance, Munich, Germany
,
Georg Wolff
1  Department of Cardiology, Pulmonology, and Vascular Medicine, Cardiovascular Research Institute Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf, Düsseldorf, Germany
,
Thomas Hohlfeld
4  Instituton of Pharmacology and Clinical Pharmacology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
,
Tobias Zeus
1  Department of Cardiology, Pulmonology, and Vascular Medicine, Cardiovascular Research Institute Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf, Düsseldorf, Germany
,
Malte Kelm
1  Department of Cardiology, Pulmonology, and Vascular Medicine, Cardiovascular Research Institute Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf, Düsseldorf, Germany
,
2  Department of Cardiology, LMU München, Munich, Germany
3  DZHK (German Centre for Cardiovascular Research), Munich Heart Alliance, Munich, Germany
› Author Affiliations
Funding This work was supported by the Forschungskommission of the Medical Faculty of the Heinrich Heine University [No. 18–2019 to A.P.; No. 2019–29 to L.D., No. 2018–32 to G.W.] and by the German Research Foundation (PO 2247/2–1 and SFB1116 to A.P and PE2704/2–1 to T.P..), by Deutsche Herzstiftung (F/04/19 shared with Dr. Lüsebrink).

Abstract

Nonvitamin K oral anticoagulants (NOACs) or direct oral anticoagulants comprise inhibitors of factor Xa (rivaroxaban, apixaban, edoxaban) or factor IIa (dabigatran). Both classes efficiently interfere with the final or penultimate step of the coagulation cascade and showed superior net clinical benefit compared with vitamin K antagonists for prevention of thromboembolic events in patients with AF and for prevention and therapy of deep vein thrombosis and pulmonary embolism. None the less, accumulating data suggested, that there may be differences regarding the frequency of atherothrombotic cardiovascular events between NOACs. Thus, the optimal individualized NOAC for each patient remains a matter of debate. Against this background, some basic and translational analyses emphasized NOAC effects that impact on platelet activity and arterial thrombus formation beyond inhibition of plasmatic coagulation. In this review, we will provide an overview of the available clinical and translational evidence for so-called noncanonical NOAC effects on platelet activation and arterial thrombosis.

Authors' Contributions

A.P., L.D., and T.P. wrote the initial draft of the manuscript and later finalized the manuscript. M.K. gave valuable input to the manuscript. G.W., M.T., M.O. T.Z., and T.H. revised the manuscript.


* Both authors contributed equally.




Publication History

Received: 31 March 2020

Accepted: 01 August 2020

Publication Date:
17 September 2020 (online)

Georg Thieme Verlag KG
Stuttgart · New York