Does the VWF:CB Assay Help to Diagnose Von Willebrand Factor Deficiency in Patients with a Bleeding Disorder of Unknown Cause?

INTRODUCTION:The entity entitled bleeding disorder of unknown cause (BDUC) qualifies individuals displaying a mild haemorrhagic profile but normal routine coagulation tests. This study was designed to evaluate whether collagen-binding assay for von Willebrand Factor (VWF) measurement (VWF:CB) could allow to diagnose VW disease in such patients. METHODS:A large screening was conducted prospectively in two University Hospitals, using the bleeding assessment tool (BAT) recommended by the International Society of Thrombosis and Hemostasis. Patients with an abnormal BAT were confirmed to have a normal complete hemostatic evaluation. A large range of VWF assays was then carried out on a new blood sample for the 68 individuals (91% women) thus identified. Of note, five VWF:CB using different types of collagen were performed, as well as a comprehensive sequencing of the VWF gene. RESULTS:Of this cohort, only 3 individuals (all blood group O), had a VWF:CB between 40 and 50 IU/dL. No unknown anomaly of the VWF gene was disclosed. Of note, 54% of these patients had unexplained abnormal occlusion times on PFA-200. CONCLUSION:This study identified 68 cases of BDUC, after screening of a large population, indicating a low incidence. Only 3 cases were potentially confirmed as displaying moderate von Willebrand disease. VWF:CB tests were globally normal in the 65 other patients of the cohort. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT0279220.