Genetic Testing for the Diagnosis of Von Willebrand Disease: Benefits and Limitations

Favaloro E J, Krigstein M, Koutts J, Brighton T, Linderman R.  Genetic Testing for the Diagnosis of Von Willebrand Disease:  Benefits and Limitations.  Journal of Coagulation Disorders, July 2010; 2(2):  37-47

REVIEW ARTICLE

Emmanuel J Favaloro^1, Michael Krigstein^2, Jerry Koutts^1, Timothy Brighton² and Robert Lindeman²

Affiliations: ¹Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, NSW, Australia and ²Department of Haematology, South Eastern Area Laboratory Service (SEALS), Randwick, NSW, Australia


ABSTRACT

von Willebrand disease (VWD) is the most common inherited bleeding disorder and arises from deficiencies and/or defects in the plasma protein von Willebrand factor (VWF). VWD is classified into six different types, with Type 1 identified as a (partial) quantitative deficiency of VWF, Type 3 a (virtually) total deficiency of VWF, and Type 2 identifying four separate types (2A, 2B, 2M, 2N) characterized by qualitative defects. The classification is currently based on phenotypic assays, supplemented by multimeric analysis of the von Willebrand protein. Although genetic analysis is not required in order to diagnose VWD or to define a patient's VWD classification type, genetic analysis may be useful in discrete situations, in order to confirm or assist the diagnosis. In particular, genetic analysis may be useful in: (i) Type 2N VWD (primarily as an aid to discriminate this from hemophilia A/carrier); (ii) Type 2B VWD (primarily as an aid to discriminate this from PT-VWD); (iii) Type 3 VWD (for prenatal assessment/family studies and alloantibody risk assessment); and perhaps also in (iv) other Type 2 VWD investigations; and (v) very select Type 1 VWD investigations (eg, VWF levels are <25 IU/mL, or family studies where causative mutation is already known). However, genetic testing should not be used as a surrogate for a poor phenotypic test approach, and it is important that a thorough phenotypic workup be applied prior to requesting genetic testing in VWD.

Keywords: von Willebrand disease, VWD, diagnosis, genetic testing, molecular analysis

Correspondence: Emmanuel J Favaloro, Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, WSAHS, Westmead, NSW 2145, Australia. Tel: +612 9845 6618; Fax: +612 9689 2331; e-mail: emmanuel.favaloro@swahs.health.nsw.gov.au