Thromb Haemost 2017; 117(08): 1651-1659
DOI: 10.1160/TH16-11-0856
Atherosclerosis and Ischaemic Disease
Schattauer GmbH

Recombinant GPVI-Fc added to single or dual antiplatelet therapy in vitro prevents plaque-induced platelet thrombus formation

Ann-Katrin Mojica Muñoz
1   Institute for the Prevention of Cardiovascular Diseases, LMU Munich, Munich, Germany
Janina Jamasbi
1   Institute for the Prevention of Cardiovascular Diseases, LMU Munich, Munich, Germany
Kerstin Uhland
2   advanceCOR GmbH, Munich, Germany
Heidrun Degen
2   advanceCOR GmbH, Munich, Germany
Götz Münch
2   advanceCOR GmbH, Munich, Germany
Martin Ungerer
2   advanceCOR GmbH, Munich, Germany
Richard Brandl
3   St. Mary’s Square Institute for Vascular Surgery and Phlebology, Munich, Germany
Remco Megens
1   Institute for the Prevention of Cardiovascular Diseases, LMU Munich, Munich, Germany
4   Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
Christian Weber
1   Institute for the Prevention of Cardiovascular Diseases, LMU Munich, Munich, Germany
5   DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany
Reinhard Lorenz
1   Institute for the Prevention of Cardiovascular Diseases, LMU Munich, Munich, Germany
Wolfgang Siess
1   Institute for the Prevention of Cardiovascular Diseases, LMU Munich, Munich, Germany
5   DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany
› Author Affiliations
Financial support: The study was supported by grants from the Medical Faculty, LMU Munich (FöFoLe Reg.-Nr.22/2014 to A-K MM), the Bayerische Forschungsstiftung (AZ 1145–14), the Deutsche Forschungsgemeinschaft (SFB1123/Z01) and the August-Lenz foundation.
Further Information

Publication History

Received: 15 November 2016

Accepted after major revision: 04 May 2017

Publication Date:
22 November 2017 (online)


The efficiency of current dual antiplatelet therapy might be further improved by its combination with a glycoprotein (GP) VI-targeting strategy without increasing bleeding. GPVI-Fc, a recombinant dimeric fusion protein binding to plaque collagen and concealing binding sites for platelet GPVI, acts as a lesion-focused antiplatelet drug, and does not increase bleeding in vivo. We investigated, whether GPVI-Fc added in vitro on top of acetylsalicylic acid (ASA), the P2Y12 antagonist ticagrelor, and the fibrinogen receptor antagonist abciximab alone or in combination would increase inhibition of platelet activation by atherosclerotic plaque. Under static conditions, GPVI-Fc inhibited plaque-induced platelet aggregation by 53%, and increased platelet inhibition by ASA (51%) and ticagrelor (64%) to 66% and 80%, respectively. Under arterial flow, GPVI-Fc inhibited plaque-induced platelet aggregation by 57%, and significantly increased platelet inhibition by ASA (28%) and ticagrelor (47%) to about 81% each. The triple combination of GPVI-Fc, ASA and ticagrelor achieved almost complete inhibition of plaque-induced platelet aggregation (93%). GPVI-Fc alone or in combination with ASA or ticagrelor did not increase closure time measured by the platelet function analyzer (PFA)-200. GPVI-Fc added on top of abciximab, a clinically used anti-fibrinogen receptor antibody which blocks platelet aggregation, strongly inhibited total (81%) and stable (89%) platelet adhesion. We conclude that GPVI-Fc added on top of single or dual antiplatelet therapy with ASA and/or a P2Y12 antagonist is likely to improve anti-atherothrombotic protection without increasing bleeding risk. In contrast, the strong inhibition of platelet adhesion by GPVI-Fc in combination with GPIIb/IIIa inhibitors could be harmful.

Note: The review process for this manuscript was fully handled by Gregory Y. H. Lip, Editor in Chief.

Supplementary Material to this article is available at

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