Agulia O'Donnell Novel therapies for haemophilia A – the role of the von Willebrand factor chaperone.manuscript.pdf (628.24 kB)

Novel therapies for hemophilia A – the role of the von Willebrand factor chaperone

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journal contribution
posted 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.

History

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 Citation

Aguila 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 Date

16 January 2019

PubMed ID

30652400

Department/Unit

  • Irish Centre for Vascular Biology
  • School of Pharmacy and Biomolecular Sciences

Research Area

  • Vascular Biology

Publisher

Wiley

Version

  • Accepted Version (Postprint)