Factor VIII: Long-established role in haemophilia A and emerging evidence beyond haemostasis
| Autor: | Michael Recht, Bethany T. Samuelson Bannow, Robert Klamroth, Cedric Hermans, Erik Berntorp, Claude Negrier, Tadashi Matsushita, Maria Elisa Mancuso, Jamie O'Hara, Elena Santagostino, Craig M. Kessler, Hermann Eichler |
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| Přispěvatelé: | UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, UCL - (SLuc) Service d'hématologie, UCL - (SLuc) Centre de malformations vasculaires congénitales |
| Rok vydání: | 2019 |
| Předmět: |
FVIII
Haemophilia Thrombin generation congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty animal diseases Haemophilia A Hemorrhage Comorbidity Hemophilia A Bioinformatics Factor IXa 03 medical and health sciences 0302 clinical medicine Von Willebrand factor hemic and lymphatic diseases Internal medicine medicine Animals Humans Risk factor Blood Coagulation Hemostasis Factor VIII Hematology biology Prophylaxis business.industry Thrombin Brain medicine.disease Blood Coagulation Factors Oncology Coagulation RANKL 030220 oncology & carcinogenesis Mutation biology.protein Angiogenesis Bone density business 030215 immunology |
| Zdroj: | Blood reviews, Vol. 35, p. 43-50 (2019) |
| ISSN: | 0268-960X |
| DOI: | 10.1016/j.blre.2019.03.002 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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