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Thromb Haemost 2025; 125(01): 036-045
DOI: 10.1055/s-0044-1787720
Coagulation and Fibrinolysis

Prethrombin-1 as a Drug Substance Promoting Hemostasis with Reduced Risk of Thrombosis

Johann Georg Graus
1   Biomedizinische Forschung and Bio-Produkte AG, Vienna, Austria
,
Michael Prückler
2   Center for Biomedical Research and Translational Surgery, Medical University of Vienna, Vienna, Austria
,
Helga Bergmeister
2   Center for Biomedical Research and Translational Surgery, Medical University of Vienna, Vienna, Austria
,
Christoph Mader
1   Biomedizinische Forschung and Bio-Produkte AG, Vienna, Austria
,
Alexandru Trefilov
1   Biomedizinische Forschung and Bio-Produkte AG, Vienna, Austria
,
Richard Gölles
1   Biomedizinische Forschung and Bio-Produkte AG, Vienna, Austria
,
Marianne Kunschak
1   Biomedizinische Forschung and Bio-Produkte AG, Vienna, Austria
,
Wolfgang Schramm
3   Ludwig-Maximilians University (LMU), Department of Transfusion Medicine and Haemostaseology, Rudolf Marx Stiftung Munich, München, Germany
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Abstract

Introduction Prethrombin-1 is a Gla-domain lacking enzymatically inactive split product that results from the cleavage of fragment 1 from prothrombin by thrombin in a feedback reaction.

Methods A prethrombin-1 preparation derived from human plasma was tested for its hemostatic and thrombogenic properties. Animal models of nail clipping (for rabbits) and tail clipping (for mice) were developed to measure blood loss in FVIII-inhibitor or rivaroxaban anticoagulated rabbits and mice, respectively. A modified Wessler test was used in rabbits to assess the thrombogenic potential by Wessler score and clot weight. Studies were performed in groups of three to six for prethrombin-1 dose escalation and comparison with prothrombin, Beriplex®, FEIBA®, and saline as a control. Data were analyzed using t-statistics or the Mann Whitney U test as applicable.

Results Prethrombin-1 has excellent hemostatic properties in anticoagulated mouse and rabbit bleeding models. Wessler tests suggest that in contrast to activated and nonactivated prothrombin complexes, prethrombin-1 has negligible thrombogenic potential.

Conclusion The thrombin zymogen prethrombin-1 promotes hemostasis with reduced risk of thrombosis. Prethrombin-1 may have potential to become a life-saving treatment for patients who bleed or are at risk of bleeding.

Keywords

coagulation - vitamin K-dependent proenzyme - clotting factors - prothrombin - prethrombin-1

Authors' Contribution

J.G.G. wrote the first draft, conceived the project, and supervised experiments. J.G.G., M.P., H.B., C.M., A.T., and R.G. designed and performed experiments, analyzed, and interpreted data. J.G.G., M.P., H.B., C.M., A.T., R.G., M.K., and W.S. contributed to the concept, literature search, and conclusions. All authors edited the final version.




Publication History

Received: 27 December 2023

Accepted: 23 May 2024

Article published online:
12 June 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Stuttgart · New York

 

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