Philadelphia-negative myeloproliferative neoplasms and acquired von Willebrand syndrome: only pertinent at diagnosis?
Key claim: Acquired von Willebrand syndrome is present in over one-third of newly diagnosed PV, ET, and prefibrotic MF patients, associates independently with female sex, thrombocytosis >700×10⁹/L and polycythemia (overall proliferative burden), links to prior bleeding but not to long-term hemorrhage- or thrombosis-free survival, and nearly always corrects on follow-up.
Abstract
BACKGROUND: Philadelphia-negative myeloproliferative neoplasms (MPNs) are associated with both thrombotic and bleeding complications. Acquired von Willebrand syndrome (AVWS) is particularly reported in essential thrombocythemia (ET), and its role in bleeding risk remains uncertain. OBJECTIVES: This study characterized patients with AVWS at the time of MPN diagnosis and evaluated the association with clinical events. METHODS: In our single-center cohort study, 178 patients diagnosed with polycythemia vera (PV), ET, or prefibrotic myelofibrosis (pre-PMF) were included. AVWS was assessed at diagnosis and was defined by a von Willebrand factor:glycoprotein IbM/von Willebrand factor:Ag ratio of <0.65. RESULTS: Prevalence of AVWS was 38% in the whole cohort (46.3% in PV, 33% in ET, and 36.4% in pre-PMF cases). Patients with AVWS showed a more proliferative profile with elevated platelets, leukocytes, hematocrit, and lactate dehydrogenase levels. The incidence of AVWS increased with the number of elevated blood cell counts, particularly in patients with 3 myeloid lineages implications (OR, 6.14; 95% CI, 2.22-18.9;< .001). In multivariable models, female sex (OR, 2.52; 95% CI, 1.15-5.78;= .02), thrombocytosis of >700 × 10/L (OR, 10; 95% CI, 4.48-24.3;< .001) and polycythemia (OR, 3.75; 95% CI, 1.54-9.61;= .004) remained independently associated with AVWS. History of bleeding was significantly higher in patients with AVWS (17.65% vs 5.5%;= .018). Hemorrhage-free survival and thrombosis-free survival were comparable between the 2 groups (= .45 and= .61, respectively). All except 1 patient corrected their ratio during follow-up. CONCLUSION: AVWS affects over one-third of newly diagnosed patients with MPN, particularly women or those with thrombocytosis or polycythemia. These results suggest AVWS is not solely driven by extreme thrombocytosis but also by overall myeloproliferative burden.
Why this matters
AVWS has historically been framed as an ET-and-extreme-thrombocytosis problem, but this cross-subtype cohort shows it is equally prevalent at diagnosis across PV, ET, and prefibrotic MF and tracks with overall proliferative burden — with polycythemia itself an independent driver. Because AVWS correlates with prior bleeding but not with long-term hemorrhage- or thrombosis-free survival and nearly always corrects on follow-up, its clinical value is anchored to the diagnosis window, informing perioperative and antiplatelet decisions during initial workup rather than long-term risk stratification.