Anti-tissue factor pathway inhibitor (TFPI) therapy: a novel approach to the treatment of haemophilia

  • Pratima ChowdaryEmail author
Progress in Hematology Current progress and future direction in the treatment for hemophilia


Novel approaches to the treatment of haemophilia are needed due to the limitations of the current standard of care, factor replacement therapy. Aspirations include lessening the treatment burden and effectively preventing joint damage. Treating haemophilia by restoring thrombin generation may be an effective approach. A promising target for restoring thrombin generation is tissue factor pathway inhibitor (TFPI), a multivalent Kunitz-type serine protease inhibitor that regulates tissue factor-induced coagulation via factor Xa-dependent feedback inhibition of the tissue factor–factor VIIa complex. Inhibition of TFPI reverts the coagulation process to a more primitive state evolutionarily, whilst regulation by other natural inhibitors is preserved. An aptamer and three monoclonal antibodies directed against TFPI have been investigated in clinical trials. As well as improving thrombin generation in the range associated with mild haemophilia, anti-TFPI therapies have the advantage of subcutaneous administration. However, the therapeutic window needs to be defined along with the potential for complications due to the novel mechanism of action. This review provides an overview of TFPI, its role in normal coagulation, the rationale for TFPI inhibition, and a summary of anti-TFPI therapies, previously or currently in development.


Tissue factor pathway inhibitor Haemophilia Monoclonal antibodies Coagulation 


Compliance with ethical standards

Conflict of interest

PC has worked as an investigator on the anti-TFPI mAb for Novo Nordisk and Bayer; has received honoraria from Baxalta/Shire, Biogen Idec, CSL Behring, Novo Nordisk, Pfizer, Roche, and Sobi; has served on advisory boards for Bayer, Baxalta/Shire, Biogen Idec, CSL Behring, Chugai, Freeline, Novo Nordisk, Pfizer, Roche, and Sobi; and has received research funding from Bayer, CSL Behring, Novo Nordisk, Pfizer, and SOBI.


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© The Japanese Society of Hematology 2018

Authors and Affiliations

  1. 1.KD Haemophilia and Thrombosis CentreRoyal Free London NHS Foundation TrustLondonUK

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