Citation
J Haem Pract 2016; 3(1):47-50. doi: 10.17225/jhp00065

Authors: Sabia Rashid, Patricia Bignell, David Keeling, Nicola Curry

Sabia Rashid
Oxford Haemophilia & Thrombosis Centre, Oxford University Hospitals NHS Trust, Churchill Hospital, Oxford, UK.

Patricia Bignell
Molecular Genetics Laboratory, Oxford University Hospitals NHS Trust, John Radcliffe Hospital, Oxford, UK.

David Keeling
Oxford Haemophilia & Thrombosis Centre, Oxford University Hospitals NHS Trust, Churchill Hospital, Oxford, UK.

Nicola Curry
Oxford Haemophilia & Thrombosis Centre, Oxford University Hospitals NHS Trust, Churchill Hospital, Oxford, UK. Email: nicola.curry@ouh.nhs.uk

Abstract

We report a single centre’s experience of the diagnosis and management of an uncommon form of type 2 von Willebrand disease (VWD) in members of two unrelated families. The affected patients presented with mild to moderate bleeding phenotypes and accompanying MCMDM-1 VWD bleeding assessment tool scores of 5 or less. Genetic analysis in both families confirmed a missense mutation in exon 30 of the von Willebrand factor (VWF) gene, a single base substitution T>A at nucleotide 5282 which led to change at codon 1761 from methionine to lysine (M1761K). This mutation lies within the A3 domain of the VWF protein, a region that is important for collagen binding. All affected patients were found to have normal coagulation profiles, normal VWF multimers and normal VWF assays except the VWF collagen-binding (VWF: CB) assay levels, which were significantly reduced. Desmopressin resulted in a good response in all treated patients, with a 3- to 5-fold rise of VWF:CB levels. However, there was variability in the degree to which VWF:CB levels remained elevated. Surgical procedures, including the delivery of one patient, were able to be managed with either desmopressin and/or tranexamic acid alone, with little need for recourse to VWF factor concentrate therapy.

Acknowledgements

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

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