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Toward personalized treatment for patients with low von Willebrand factor and quantitative von Willebrand disease

journal contribution
posted on 01.07.2021, 16:27 by James O'DonnellJames O'Donnell
The biological mechanisms involved in the pathogenesis of type 2 and type 3 von Willebrand disease (VWD) have been studied extensively. In contrast, although accounting for the majority of VWD cases, the pathobiology underlying partial quantitative VWD has remained somewhat elusive. However, important insights have been attained following several recent cohort studies that have investigated mechanisms in patients with type 1 VWD and low von Willebrand factor (VWF), respectively. These studies have demonstrated that reduced plasma VWF levels may result from either (1) decreased VWF biosynthesis and/or secretion in endothelial cells and (2) pathological increased VWF clearance. In addition, it has become clear that some patients with only mild to moderate reductions in plasma VWF levels in the 30 to 50 IU/dL range may have significant bleeding phenotypes. Importantly in these low VWF patients, bleeding risk fails to correlate with plasma VWF levels and inheritance is typically independent of the VWF gene. Although plasma VWF levels may increase to > 50 IU/dL with progressive aging or pregnancy in these subjects, emerging data suggest that this apparent normalization in VWF levels does not necessarily equate to a complete correction in bleeding phenotype in patients with partial quantitative VWD. In this review, these recent advances in our understanding of quantitative VWD pathogenesis are discussed. Furthermore, the translational implications of these emerging findings are considered, particularly with respect to designing personalized treatment plans for VWD patients undergoing elective procedures.

Funding

NIH for the Zimmerman Program (HL081588)

Foundation Ireland Principal Investigator Award (11/PI/1066)

Health Research Board Investigator Lead Project Award (ILP-POR-2017-008)

National Children’s Research Centre Project Award (C/18/1)

History

Comments

The original article is available at https://www.thieme-connect.com

Published Citation

O'Donnell JS. Toward personalized treatment for patients with low von Willebrand factor and quantitative von Willebrand disease. Semin Thromb Hemost. 2021;47(2):192-200.

Publication Date

26 February 2021

PubMed ID

33636750

Department/Unit

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

Research Area

  • Vascular Biology

Publisher

Georg Thieme Verlag KG

Version

  • Accepted Version (Postprint)