Clinical and Laboratory Characterization of Acquired Von Willebrand Syndrome

Acquired von Willebrand Syndrome (AVWS) is a rare bleeding disorder characterized by quantitative or qualitative defects of von Willebrand factor (VWF) in patients without a personal or family history of bleeding. It is frequently associated with systemic diseases, particularly lymphoproliferative disorders (LPDs) and myeloproliferative neoplasms (MPNs). In this single-center, retrospective cross-sectional study, we included patients diagnosed with AVWS at the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center between April 2014 and March 2025. Bleeding severity was assessed using the ISTH-BAT score. Laboratory tests included FVIII:C, VWF:Ag, VWF:GPIbR, VWF:RCo, VWF:CB, VWFpp, and multimer analysis. Among 140 patients, 106 (76%) had MPNs and 26 (19%) LPDs. At least one bleeding symptom was observed in 70% of patients, with clinically significant bleeding occurring in 24% of the cohort. Clinically relevant bleeding (mainly mucocutaneous and gastrointestinal) was more frequent and severe in LPDs (58%) than in MPNs (13%). LPDs showed severe VWF functional defects, marked HMWM loss, and elevated VWFpp/VWF:Ag ratios (median 6.7), consistent with accelerated clearance. MPNs displayed mild HMWM reduction, normal clearance (median VWFpp/VWF:Ag ratio 1.0), and an inverse correlation between platelet count and the degree of HMWM depletion (ρ = -0.48, p < 0.001). Bleeding severity correlated inversely with VWF:GPIbR in LPDs (ρ = -0.50, p = 0.02) and with VWF:RCo in MPNs. Anti-VWF antibodies were found in 30% of tested LPDs or autoimmune cases. The two main phenotypes presented in AVWS were immune-mediated in LPDs and platelet-mediated in MPNs. Understanding the underlying mechanism is crucial for accurate diagnosis and targeted treatment to reduce bleeding risk and improve outcomes.