Why is Misdiagnosis of von Willebrand Disease Still Prevalent and How Can We Overcome It? A Focus on Clinical Considerations and Recommendations

Abstract

Chanukya K Colonne,1,* Benjamin Reardon,1,* Jennifer Curnow,2– 4 Emmanuel J Favaloro1,4,5 1Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), NSW Health Pathology, Westmead Hospital, Sydney, NSW, Australia; 2Department of Clinical Haematology, Westmead Hospital, Sydney, NSW, Australia; 3Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia; 4Sydney Centres for Thrombosis and Haemostasis, Sydney, NSW, Australia; 5School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, NSW, Australia*These authors contributed equally to this workCorrespondence: Emmanuel J FavaloroDepartment of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead, Sydney, NSW, 2145, AustraliaTel [phone]Fax [phone]Email [email protected]: Despite von Willebrand disease (VWD) being the most common inherited bleeding disorder, its accurate diagnosis is frequently shrouded by diagnostic pitfalls. VWD is frequently under-diagnosed, over-diagnosed and misdiagnosed, leading to significant avoidable patient morbidity and health care system burden. At the heart of this dilemma lies the heterogeneity and complexity of von Willebrand factor (VWF) and associated defects, and the necessity of coalescing clinical and laboratory features to obtain an accurate diagnosis. Common pitfalls include poor clinical and scientific understanding and familiarity with VWD, incomplete clinical history and lack of routine use of standardised bleeding assessment tools (BAT), difficulty in accessing a comprehensive repertoire of laboratory tests, significant pre-analytical, analytical and post-analytical issues, and lack of expertise in laboratory testing and interpretation. Errors, resulting in under-diagnosis, over-diagnosis, and misdiagnosis of VWD, are presented and discussed. Strategies to minimise errors include better education of clinicians and laboratory staff on VWD, routine use of validated BAT, utilising a comprehensive gamut of laboratory investigations according to a standardised algorithm, and repeating testing to minimise pre-analytical errors. Recommendations on appropriate patient selection for VWD testing, how VWD should be investigated in the laboratory, and how to ensure test results are accurately interpreted in the correct clinical context are detailed.Keywords: von Willebrand disease, VWD, diagnosis

Keywords

• von willebrand disease
• vwd
• diagnosis