Thromb Haemost 2020; 120(11): 1548-1556
DOI: 10.1055/s-0040-1715445
Cellular Haemostasis and Platelets

Supplemental Fibrinogen Restores Platelet Inhibitor-Induced Reduction in Thrombus Formation without Altering Platelet Function: An In Vitro Study

Thomas Bärnthaler
1  Otto Loewi Research Center, Division of Pharmacology Medical University of Graz, Graz, Austria
,
Elisabeth Mahla
2  Division of Anaesthesiology for Cardiovascular and Thoracic Surgery and Intensive Care Medicine, Department of Anesthesiology and Intensive Care Medicine, Medical University of Graz, Graz, Austria
,
Gabor G. Toth
3  Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
,
Rufina Schuligoi
1  Otto Loewi Research Center, Division of Pharmacology Medical University of Graz, Graz, Austria
,
Florian Prüller
4  Clinical Institute of Medical Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
,
Eva Buschmann
3  Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
,
Akos Heinemann
1  Otto Loewi Research Center, Division of Pharmacology Medical University of Graz, Graz, Austria
› Author Affiliations
Funding This research was supported by the Austrian Science Fund FWF (Grant P22521-B18 to A.H. and P26185-B19 to R.S.) and the Jubiläumsfonds of the Austrian National Bank (14263 to A.H.). T.B. was funded by the PhD Program DK-MOLIN (FWF–W1241). T.B. is a recipient of a DOC Fellowship of the Austrian Academy of Sciences and the Start Funding Program of the Medical University of Graz.

Abstract

Background For patients treated with dual antiplatelet therapy, standardized drug-specific 3-to-7 day cessation is recommended prior to major surgery to reach sufficient platelet function recovery. Here we investigated the hypothesis that supplemental fibrinogen might mitigate the inhibitory effects of antiplatelet therapy.

Methods and Results To this end blood from healthy donors was treated in vitro with platelet inhibitors, and in vitro thrombus formation and platelet activation were assessed. Ticagrelor, acetylsalicylic acid, the combination of both, and tirofiban all markedly attenuated the formation of adherent thrombi, when whole blood was perfused through collagen-coated microchannels at physiological shear rates. Addition of fibrinogen restored in vitro thrombus formation in the presence of antiplatelet drugs and heparin. However, platelet activation, as investigated in assays of P-selectin expression and calcium flux, was not altered by fibrinogen supplementation. Most importantly, fibrinogen was able to restore in vitro thrombogenesis in patients on maintenance dual antiplatelet therapy after percutaneous coronary intervention.

Conclusion Thus, our in vitro data support the notion that supplementation of fibrinogen influences the perioperative hemostasis in patients undergoing surgery during antiplatelet therapy by promoting thrombogenesis without significantly interfering with platelet activation.

Authors' Contributions

Thomas Bärnthaler, Gabor G. Toth, Rufina Schuligoi, Florian Prüller, and Eva Buschmann performed the experiments; Thomas Bärnthaler, Elisabeth Mahla, Akos Heinemann, Florian Prüller, and Rufina Schuligoi interpreted the results of the experiments; Thomas Bärnthaler and Rufina Schuligoi prepared the figures; Thomas Bärnthaler, Rufina Schuligoi, Akos Heinemann, and Elisabeth Mahla drafted the manuscript. Thomas Bärnthaler, Rufina Schuligoi, Akos Heinemann, and Elisabeth Mahla revised the manuscript; Thomas Bärnthaler, Gabor G. Toth, Rufina Schuligoi, Florian Prüller, Eva Buschmann, Akos Heinemann, and Elisabeth Mahla approved the final version of the manuscript; Akos Heinemann, Thomas Bärnthaler, Rufina Schuligoi, and Elisabeth Mahla conceptualized and designed the research.




Publication History

Received: 30 September 2019

Accepted: 25 June 2020

Publication Date:
09 August 2020 (online)

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