Novel therapies for hemophilia A – the role of the von Willebrand factor chaperone
journal contributionposted on 30.07.2021, 14:18 by Sonia Aguila Martinez, James O'DonnellJames O'Donnell
The factor VIII–von Willebrand factor (VWF) complex
FVIII is a plasma sialoglycoprotein that plays a critical role in maintaining normal hemostasis. Patients with severe hemophilia A have markedly reduced plasma FVIII levels, and thus typically show a significant bleeding phenotype. Accumulating data suggest that plasma FVIII is predominantly derived from biosynthesis within sinusoidal cells and endothelial cells (ECs), particularly in the liver and lung 1. FVIII is initially synthesized as an inactive 2332 amino acid polypeptide composed of three distinct domain types: A, B, and C (domain structure A1–a1–A2–a2–B–a3–A3–C1–C2). Prior to secretion, this single‐chain FVIII undergoes complex post‐translational modification that includes significant glycosylation, sulfation, and limited intracellular proteolytic processing. Consequently, plasma FVIII circulates as a heterodimeric protein consisting of a heavy chain (A1–a1–A2–a2–B) and a light chain (a3–A3–C1–C2), held together through a metal ion‐dependent interaction.
Comments"This is the pre-peer reviewed version of the following article: [Aguila S, O'Donnell JS. Novel therapies for hemophilia A - the role of the von Willebrand factor chaperone. Journal of Thrombosis and Haemostasis. 2019 Mar;17(3):426-428., which has been published in final form at https://doi.org/10.1111/jth.14353. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."
Published CitationAguila S, O'Donnell JS. Novel therapies for hemophilia A - the role of the von Willebrand factor chaperone. Journal of Thrombosis and Haemostasis. 2019;17(3):426-428.
Publication Date16 January 2019
- Irish Centre for Vascular Biology
- School of Pharmacy and Biomolecular Sciences
- Vascular Biology
- Accepted Version (Postprint)