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Hamostaseologie 2023; 43(01): 044-051
DOI: 10.1055/a-1980-8198
Review Article

Low von Willebrand Disease: A Bleeding Disorder of Unknown Cause?

James S. O'Donnell 
1   Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin 2, Ireland
2   National Coagulation Centre, St James's Hospital, Dublin, Ireland
3   Irish-Australian Blood Collaborative (IABC) Network, Dublin, Ireland
,
Ross I. Baker
3   Irish-Australian Blood Collaborative (IABC) Network, Dublin, Ireland
4   Western Australia Centre for Thrombosis and Haemostasis, Perth Blood Institute, Murdoch University, Perth, Australia
5   Hollywood Haemophilia Treatment Centre, Hollywood Hospital, Perth, Australia
› Author Affiliations Funding Science Foundation Ireland, Frontiers for the Future (FFP) Award (20/FFP-A/895)
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Abstract

von Willebrand disease (VWD) represents the most common inherited bleeding disorder. The majority of VWD cases are characterized by partial quantitative reductions in plasma von Willebrand factor (VWF) levels. Management of patients with mild to moderate VWF reductions in the range of 30 to 50 IU/dL poses a common clinical challenge. Some of these low VWF patients present with significant bleeding problems. In particular, heavy menstrual bleeding and postpartum hemorrhage can cause significant morbidity. Conversely, however, many individuals with mild plasma VWF:Ag reductions do not have any bleeding sequelae. In contrast to type 1 VWD, most patients with low VWF do not have detectable pathogenic VWF sequence variants, and bleeding phenotype correlates poorly with residual VWF levels. These observations suggest that low VWF is a complex disorder caused by variants in other genes beyond VWF. With respect to low VWF pathobiology, recent studies have shown that reduced VWF biosynthesis within endothelial cells likely plays a key role. However, pathological enhanced VWF clearance from plasma has also been described in approximately 20% of low VWF cases. For low VWF patients who require hemostatic treatment prior to elective procedures, tranexamic acid and desmopressin have both been shown to be efficacious. In this article, we review the current state of the art regarding low VWF. In addition, we consider how low VWF represents an entity that appears to fall between type 1 VWD on the one hand and bleeding disorders of unknown cause on the other.

Keywords

von Willebrand factor - von Willebrand disease - low VWF

Authors' Contribution

R.I.B. and J.S.O'D. were involved in writing and reviewing the paper.




Publication History

Received: 02 October 2022

Accepted: 15 November 2022

Article published online:
20 February 2023

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