CO080 | INVESTIGATING MECHANISMS OF ACQUIRED VON WILLEBRAND SYNDROME ACROSS HEMATOLOGICAL DISEASES: THE CONTRIBUTION OF INTRAPLATELET VWF
Abstract
Background. Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder due to reduced or dysfunctional von Willebrand factor (VWF) in patients without a personal or family bleeding history. It is commonly associated with myeloproliferative neoplasms (MPNs) and lymphoproliferative disorders (LPDs). The contribution of platelet VWF stores is less defined. Aims. To characterize AVWS phenotypes in a single-center cohort, focusing on intraplatelet VWF. Methods. We retrospectively included AVWS patients diagnosed between April 2014 and March 2025. Bleeding severity was assessed by ISTH-BAT. Testing included FVIII:C, VWF:Ag, VWF:GPIbR, VWF:RCo, VWF:CB, VWF propeptide (VWFpp), and multimer analysis. In a subset, intraplatelet VWF:Ag and GPIbR activity were measured in platelet lysates from citrate blood and expressed as IU/10⁹ platelets. Results. Among 140 patients, 106 (76%) had MPNs and 26 (19%) LPDs. At least one bleeding symptom occurred in 70%, and clinically significant bleeding in 24%, more frequent/severe in LPDs (58%; mainly mucocutaneous and gastrointestinal) than in MPNs (13%). LPDs showed severe functional defects, marked high-molecular-weight multimer loss, and elevated VWFpp/VWF:Ag ratio (median 6.7), consistent with accelerated clearance; anti-VWF antibodies were detected in 30% of tested LPDs/autoimmune cases. MPNs displayed mild high-molecular-weight multimer reduction and normal clearance (median VWFpp/VWF:Ag 1.0), with an inverse correlation between platelet count and multimer 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. Intraplatelet assays were available for 38 patients (31 MPNs, 7 LPDs): MPNs had reduced intraplatelet VWF:Ag 0.18 IU/10⁹ (IQR 0.14–0.21; reference 0.22–0.60) and intraplatelet GPIbR 0.14 IU/10⁹ (0.09–0.16; reference 0.15–0.58), whereas LPDs showed higher values (VWF:Ag 0.31, 0.20–0.38; GPIbR 0.25, 0.24–0.30). Conclusions. AVWS shows two main patterns: immune/clearance-driven in LPDs and platelet-mediated in MPNs. In MPN-associated AVWS, plasma VWF:Ag may be preserved, yet reduced intraplatelet VWF suggests partial depletion of megakaryocyte/platelet VWF stores, potentially reflecting altered synthesis or sustained release. This challenges the assumption that MPN-related AVWS is confined to plasma functional defects and points to a dual endothelial and megakaryocyte/platelet contribution to the bleeding phenotype in some patients. Integrating intraplatelet VWF with plasma assays and multimer analysis may refine mechanistic phenotyping and support targeted management.
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BibTeX
@article{ciavarella2026co080,
title = {{CO080 | INVESTIGATING MECHANISMS OF ACQUIRED VON WILLEBRAND SYNDROME ACROSS HEMATOLOGICAL DISEASES: THE CONTRIBUTION OF INTRAPLATELET VWF}},
author = {Alessandro Ciavarella},
journal = {Bleeding, Thrombosis and Vascular Biology},
year = {2026},
month = oct,
url = {https://www.btvb.org/btvb/article/view/782},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - CO080 | INVESTIGATING MECHANISMS OF ACQUIRED VON WILLEBRAND SYNDROME ACROSS HEMATOLOGICAL DISEASES: THE CONTRIBUTION OF INTRAPLATELET VWF
AU - Alessandro Ciavarella
PY - 2026
DA - 2026/10/26
JO - Bleeding, Thrombosis and Vascular Biology
UR - https://www.btvb.org/btvb/article/view/782
AB - Background. Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder due to reduced or dysfunctional von Willebrand factor (VWF) in patients without a personal or family bleeding history. It is commonly associated with myeloproliferative neoplasms (MPNs) and lymphoproliferative disorders (LPDs). The contribution of platelet VWF stores is less defined. Aims. To characterize AVWS phenotypes in a single-center cohort, focusing on intraplatelet VWF. Methods. We retrospectively included AVWS patients diagnosed between April 2014 and March 2025. Bleeding severity was assessed by ISTH-BAT. Testing included FVIII:C, VWF:Ag, VWF:GPIbR, VWF:RCo, VWF:CB, VWF propeptide (VWFpp), and multimer analysis. In a subset, intraplatelet VWF:Ag and GPIbR activity were measured in platelet lysates from citrate blood and expressed as IU/10⁹ platelets. Results. Among 140 patients, 106 (76%) had MPNs and 26 (19%) LPDs. At least one bleeding symptom occurred in 70%, and clinically significant bleeding in 24%, more frequent/severe in LPDs (58%; mainly mucocutaneous and gastrointestinal) than in MPNs (13%). LPDs showed severe functional defects, marked high-molecular-weight multimer loss, and elevated VWFpp/VWF:Ag ratio (median 6.7), consistent with accelerated clearance; anti-VWF antibodies were detected in 30% of tested LPDs/autoimmune cases. MPNs displayed mild high-molecular-weight multimer reduction and normal clearance (median VWFpp/VWF:Ag 1.0), with an inverse correlation between platelet count and multimer 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. Intraplatelet assays were available for 38 patients (31 MPNs, 7 LPDs): MPNs had reduced intraplatelet VWF:Ag 0.18 IU/10⁹ (IQR 0.14–0.21; reference 0.22–0.60) and intraplatelet GPIbR 0.14 IU/10⁹ (0.09–0.16; reference 0.15–0.58), whereas LPDs showed higher values (VWF:Ag 0.31, 0.20–0.38; GPIbR 0.25, 0.24–0.30). Conclusions. AVWS shows two main patterns: immune/clearance-driven in LPDs and platelet-mediated in MPNs. In MPN-associated AVWS, plasma VWF:Ag may be preserved, yet reduced intraplatelet VWF suggests partial depletion of megakaryocyte/platelet VWF stores, potentially reflecting altered synthesis or sustained release. This challenges the assumption that MPN-related AVWS is confined to plasma functional defects and points to a dual endothelial and megakaryocyte/platelet contribution to the bleeding phenotype in some patients. Integrating intraplatelet VWF with plasma assays and multimer analysis may refine mechanistic phenotyping and support targeted management.
SN - 2785-5309
ER -