Factor VIII: Long-established role in haemophilia A and emerging evidence beyond haemostasis

Bethany Samuelson Bannow, Michael Recht, Claude Négrier, Cédric Hermans, Erik Berntorp, Hermann Eichler, Maria Elisa Mancuso, Robert Klamroth, Jamie O'Hara, Elena Santagostino, Tadashi Matsushita, Craig Kessler

Research output: Contribution to journalReview articlepeer-review

Abstract

Factor VIII protein (FVIII) as a coagulation replacement factor has for decades been used as the standard of care for management of people with haemophilia A. It is effective for treatment of bleeding events, as prophylaxis to prevent bleeding events and preserve joint function, and to support surgery in people with haemophilia A. Despite long experience in treating haemophilia A, we are only beginning to understand the functions of FVIII beyond its established role as a coenzyme to factor IXa to expedite thrombin generation through the intrinsic pathway of coagulation. Here, we review the current role of FVIII coagulant (FVIII:C) in haemophilia A management and emerging evidence for the role of FVIII across multiple systems, including the cardiovascular system, angiogenesis and maintenance of bone health. For instance, supraphysiological FVIII levels are a risk factor for venous thromboembolism. von Willebrand factor (VWF), which forms a non-covalent complex with circulating FVIII, is an established marker and regulator of angiogenesis. In a mouse model of haemophilia, treatment with FVIII decreased expression of receptor activator of nuclear factor kappa-Β ligand (RANKL), a marker for bone turnover. Longitudinal follow-up data in people with haemophilia A are needed to confirm and extend these observations.

Original languageEnglish
Pages (from-to)43-50
Number of pages8
JournalBlood Reviews
Volume35
DOIs
Publication statusPublished - May 1 2019

Keywords

  • Angiogenesis
  • Bone density
  • FVIII
  • Haemophilia
  • Prophylaxis
  • Thrombin generation

ASJC Scopus subject areas

  • Hematology
  • Oncology

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