CLINICAL AND LABORATORY CHARACTERISATION OF ACQUIRED VON WILLEBRAND SYNDROME

Background: Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder due to reduced or dysfunctional VWF in individuals without a personal or familial bleeding history. It is associated with systemic diseases such as lymphoproliferative (LPDs) and myeloproliferative neoplasms (MPNs), cardiovascular, and autoimmune conditions. The underlying biological processes differ across clinical contexts and remain incompletely defined, complicating both diagnosis and management. Aim: To characterize AVWS based on clinical presentations and laboratory profiles, with particular focus on bleeding phenotypes, multimer patterns, and underlying disease mechanisms. Methods: This cross-sectional study included patients diagnosed with AVWS between 2014 and 2025 at a single center. Clinical and laboratory data, including ISTH-BAT score, FVIII:C, VWF:Ag, VWF:RCo, VWF:GPIbR, VWF:CB, VWFpp, multimer distribution, and intraplatelet VWF, were analyzed. Comparative and correlation analyses were conducted between MPNs and LPDs subgroups. Additional analyses explored associations between functional VWF assays and clinical bleeding severity. Results: Among 140 patients diagnosed with AVWS, 76% had MPNs and 19% LPDs. Clinically relevant bleeding was more frequent and severe in LPDs, with higher ISTH-BAT scores and predominant mucosal and gastrointestinal bleedings. LPDs showed more profound laboratory alterations, including reduced VWF activity, pronounced multimeric loss, and elevated VWFpp/VWF:Ag ratios, suggesting selective clearance of high molecular weight multimers potentially associated with proteolysis. In contrast, MPNs displayed milder abnormalities, with relatively preserved multimer structure, supporting a mechanism of platelet-mediated adsorption, and reduced intraplatelet VWF content. Notably, among the two assays measuring the platelet-dependent VWF activity, VWF:RCo better correlated with bleeding severity in LPDs, while VWF:GPIbR was more sensitive in detecting qualitative functional defects in MPNs. Conclusions: AVWS is characterized by distinct pathogenetic patterns in MPNs and LPDs, that may variably involve clearance, cellular absorption, and proteolysis. Detailed investigation of these processes is essential to support targeted, mechanism-oriented management strategies.

Grantor dc:publisher

Università degli Studi di Milano

Year dc:date

2025

Author dc:creator

• CIAVARELLA, ALESSANDRO

Contributors dc:contributor

• tutor: F. Peyvandi ; coordinator: M. S. Clerici
• A. Ciavarella
• CLERICI, MARIO SALVATORE

• Settore MEDS-05/A - Medicina interna

Statement dc:rights

• info:eu-repo/semantics/openAccess
• license:Creative commons
• license uri:http://creativecommons.org/licenses/by-sa/4.0/

Language dc:language

eng

Handle dc:identifier

https://hdl.handle.net/2434/1175518

OAI identifier oai:identifier

oai:air.unimi.it:2434/1175518