Comprehensive re-evaluation of historical von Willebrand disease diagnosis in association with whole blood platelet aggregation and function

Introduction: Diagnosis of von Willebrand disease (VWD) is challenging, particularly for type 1. The current diagnostic guidelines emphasize simultaneous bleeding symptoms and von Willebrand factor (VWF) levels of <30-40 IU/dL. Historical diagnoses require updated evaluation. We assessed the accuracy of past VWD diagnoses in our comprehensive care center with the standardized bleeding score (BS) and central laboratory analysis, focusing on VWF-dependent platelet functions in whole blood. Methods: Our study comprised 83 adults with prior VWD who were diagnosed a median of 20 years ago. We assessed BS, VWF antigen and activity (minimum of 3 measurements), FVIII, PFA-100 (R), and platelet aggregation via Multiplate (R). Genetic testing was targeted to types 3, 2N, 2B, and equivocal cases. Results: All 13/13 (100%) type 3 and 29/32 (90%) type 2, but only 10/38 (26%) of type 1 (overall 52/83 (63%)) patients met the current criteria for VWD. All confirmed cases had abnormal BS, impaired PFA-100 (R), and decreased or absent ristocetin-induced platelet aggregation (RIPA), except subtype 2B. VWF, FVIII, RIPA, and PFA correlated with BS including all study subjects. Ten of the 38 patients with previous type 1 had low VWF (35-50 IU/dL) and variable VWF-dependent platelet function. Altogether, 21/83 patients (25%) had repeatedly normal VWF:RCo (>50 IU/dL). Conclusion: von Willebrand disease is associated with impaired VWF-dependent whole blood platelet functions that match traditional VWF measurements. We detected normal VWF in 25% of historically diagnosed patients, mainly type 1 patients, implying that there is a need to systematically re-evaluate historical VWD diagnoses.