CC BY 4.0 · Hamostaseologie 2020; 40(05): 606-620
DOI: 10.1055/a-1159-4273
Review Article

Origins, Development, Current Challenges and Future Directions with Activated Prothrombin Complex Concentrate for the Treatment of Patients with Congenital Haemophilia with Inhibitors

Hans H. Brackmann
1   Haemophilia Center, Institute of Experimental Haematology and Blood Transfusion, University of Bonn, Bonn, Germany
,
Wolfgang Schramm
2   Rudolf Marx-Stiftung für Hämostaseologie, Universität München and Bluterbetreuung Bayern e. V. (BBB) - Germany
,
Johannes Oldenburg
1   Haemophilia Center, Institute of Experimental Haematology and Blood Transfusion, University of Bonn, Bonn, Germany
,
Viridiana Cano
3   Shire International GmbH, a Takeda company, Zürich, Switzerland
,
Peter L. Turecek
4   Baxalta Innovations GmbH, a Takeda company, Vienna, Austria
,
Claude Négrier
5   Haemophilia and Thrombosis Centre, Louis Pradel Hospital, University Claude Bernard Lyon 1, Lyon, France
› Author Affiliations
Funding This study was supported by Baxalta US Inc., a Takeda company.

Abstract

Congenital haemophilia A (HA) is caused by deficiency of coagulation factor VIII (FVIII) activity, leading to spontaneous or traumatic bleeding events. While FVIII replacement therapy can treat and prevent bleeds, approximately 30% of patients with severe HA develop inhibitor antibodies that render FVIII replacement therapy ineffective. The bypassing agents (BPAs), activated prothrombin complex concentrate (aPCC) and recombinant activated FVII, first approved in 1977 and 1996, respectively, act to generate thrombin independent of pathways that involve factors IX and VIII. Both may be used in patients with congenital haemophilia and inhibitors (PwHIs) for the treatment and prevention of acute bleeds and quickly became standard of care. However, individual patients respond differently to different agents. While both agents are approved for on-demand treatment and perioperative management for patients with congenital haemophilia with inhibitors, aPCC is currently the only BPA approved worldwide for prophylaxis in PwHI. Non-factor therapies (NFTs) have a mechanism of action distinct from BPAs and have reported higher efficacy rates as prophylactic regimens. Nonetheless, treatment challenges remain with NFTs, particularly regarding the potential for synergistic action on thrombin generation with concomitant use of other haemostatic agents, such as BPAs, for the treatment of breakthrough bleeds and in perioperative management. Concomitant use of NFTs with other haemostatic agents could increase the risk of adverse events such as thromboembolic events or thrombotic microangiopathy. This review focuses on the origins, development and on-going role of aPCC in the evolving treatment landscape in the management of PwHI.

Authors' Contributions

All authors jointly conceived the idea for the review. All authors contributed to writing of the manuscript, and all authors critically reviewed the manuscript at each stage of development.




Publication History

Received: 12 February 2020

Accepted: 16 April 2020

Article published online:
27 July 2020

© 2020. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
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