Factors Related to the Development of Acquired Von Willebrand Syndrome in Patients with Essential Thrombocythemia and Polycythemia Vera

Objective: We characterized acquired von Willebrand syndrome (AVWS) among essential thrombocythemia (ET) and polycythemia vera (PV) patients.

Methods: A review of patients with ET or PV evaluated for AVWS.

Results: Of 116 patients with ET, 64 (55%) developed AVWS; of 57 with PV, 28 (49%) developed AVWS. Median platelet counts of ET and PV patients who developed AVWS were 920 X 10⁹/L and 679 X 10⁹/L, respectively (P=0.01). Of patients who developed AVWS, 69.5% had platelet counts below 1000 X 10⁹/L. Bleeding was more common in patients with AVWS, among both ET and PV patients (P<0.001). VWF:RCo levels and VWF:RCo/VWF:Ag ratio were lower among JAK2 V617F positive- vs. JAK2 V617F negative- ET patients (P=0.02 and P=0.002, respectively); whereas VWF:Ag levels were comparable (P=0.96). ET patients harboring the JAK2 V617F mutation were more likely to develop AVWS than were calreticulin-positive patients (70.3% vs. 45.7%, P=0.02), despite lower platelet counts (median 773 vs. 920 X 10⁹/l, P=0.05). In multivariable analysis, age (β=0.26, P=0.002), platelet count (β=-0.38, P<0.001), hemoglobin level (β=-0.22, P=0.01) and JAK2 V617F mutation (β=-0.23, P=0.01) independently predicted VWF:RCo, among ET patients; whereas only platelet count predicted VWF:RCo among PV patients (β=-0.49, P<0.001).

Conclusion: Among ET and PV patients, AVWS was common and associated with higher bleeding rates and higher platelet count; nonetheless, most AVWS patients had platelet counts under 1000 X 10⁹/L. Thus, AVWS screening should be included in routine assessment of ET and PV patients. Among ET patients, JAK2 V617F was a main driver for the development of AVWS.