Evaluation of different diagnostic tools for detection of acquired von Willebrand syndrome in patients with polycythemia vera or essential thrombocythemia

Introduction: Patients with myeloproliferative neoplasms (MPNs) are at increased risk of both thromboembolic and hemorrhagic complications. Among the risk factors for bleeding is the development of an acquired qualitative von Willebrand factor defect with loss of larger VWF plasma multimers, resulting in acquired von Willebrand syndrome (aVWS). The diagnosis of aVWS is challenging, because no single automated test is sufficient to prove or exclude aVWS. We aimed to compare different diagnostic tools used for the detection of MPN-associated aVWS in daily practice.

Methods: Patients with polycythemia vera (PV) or essential thrombocythemia (ET), who had been routinely assessed for quantitative and qualitative abnormalities of plasma VWF, were retrospectively studied.

Results: Sixty-four patients (37 with PV and 27 with ET) were analyzed. Using multimer analysis of plasma VWF, aVWS with a loss of VWF high-molecular-weight multimers was detected in 51.4 % and 55.6 % of PV and ET patients, respectively.

A vwf: GPIbM/Ag threshold of <0.8 was defined as useful screening tool for aVWS, with acceptable sensitivity (88.2 %) and specificity (76.7 %) and good agreement with VWF multimer analysis (κ = 0.653). VWF:GPIbM/Ag showed better performance than VWF:CB/Ag. Regarding hematological parameters, there was no difference in hematocrit between patients with and without aVWS. However, leukocyte and platelet counts were significantly increased in the aVWS cohort.

Conclusion: For the first time, we identified a VWF:GPIbM/Ag ratio of <0.8 as simple screening tool for aVWS in patients with PV or ET. This observation, however, should be confirmed in a larger patient cohort.