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Author Notes:

Robert F Sidonio, Aflac Cancer and Blood Disorders Center Children’s Healthcare of Atlanta, 1405 Clifton Road NE, Atlanta, GA 30322, USA. Email: robert.sidonio.jr@emory.edu

The authors would like to thank Amie Peltzer from Lucid Group Communications Ltd, Marlow, Buckinghamshire, UK, for providing medical writing support.

Y.D. has received grants and personal fees from Bayer, Baxter, Baxalta, Novo Nordisk, CSL Behring, LFB, Pfizer, LeoPharma, Octapharma, Sobi, Stago, and Takeda. M.H. has received grants and personal fees from Coagulation Sciences, CSL Behring, Novo Nordisk, Sanofi Genzyme, and Takeda. G.K. has received grants and personal fees from Alnylam, Bayer, Biomarin, BPL, CSL, Novo Nordisk, OPKO Biologics, Pfizer, Roche, Sanofi, Takeda, and UniQuore. R.F.S. has received grants and personal fees from Bayer, Genentech, Hema Biologics, Novo Nordisk, Biomarin, Octapharma, Pfizer, Roche, Sanofi, Sigilon, Sobi, Guardian Therapeutics, and Takeda.


Research Funding:

Medical writing support was funded by Sanofi in accordance with Good Publication Practice (GPP3) guidelines.


  • antithrombins
  • blood coagulation tests
  • fitusiran
  • hemophilia
  • hemostasis
  • therapies

Thrombin generation and implications for hemophilia therapies: A narrative review


Journal Title:

Research and Practice in Thrombosis and Haemostasis


Volume 7, Number 1


, Pages 100018-100018

Type of Work:

Article | Final Publisher PDF


Thrombin plays an essential role in achieving and maintaining effective hemostasis and stable clot formation. In people with hemophilia, deficiency of procoagulant factor (F)VIII or FIX results in insufficient thrombin generation, leading to reduced clot stability and various bleeding manifestations. A correlation has been found between the bleeding phenotype of people with hemophilia and the extent of thrombin generation, with individuals with increased thrombin generation being protected from bleeding and those with lower thrombin generation having increased bleeding tendency. The amount, location, and timing of thrombin generation have been found to affect the formation and stability of the resulting clot. The goal of all therapies for hemophilia is to enhance the generation of thrombin with the aim of restoring effective hemostasis and preventing or controlling bleeding; current treatment approaches rely on either replacing or mimicking the missing procoagulant (ie, FVIII or FIX) or rebalancing hemostasis through lowering natural anticoagulants, such as antithrombin. Global coagulation assays, such as the thrombin generation assay, may help guide the overall management of hemostasis by measuring and monitoring the hemostatic potential of patients and, thus, assessing the efficacy of treatment in people with hemophilia. Nevertheless, standardization of the thrombin generation assay is needed before it can be adopted in routine clinical practice.

Copyright information:

© 2023 The Authors

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