Von Willebrand factor analysis in patients with Myeloproliferative neoplasms

Abstract

Myeloproliferative neoplasms (MPNs) encompass clonal disorders including essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF). These disorders are characterised by clonal proliferation of myeloid lineage components, leading to symptoms such as agranulocytosis, erythrocytosis, and thrombocytosis. Common to these MPNs are mutually exclusive mutations in JAK2, CALR, and MPL genes, and they share a tendency toward myeloproliferation, splenomegaly, potential progression to AML or myelofibrosis, and the occurrence of thrombohemorrhagic events. Moreover, patients, especially those with ET, may develop AVWD, a qualitative defect in von Willebrand factor (VWF). To elucidate the relationship between MPNs and AVWD, this study compared the VWF profiles of MPN patients to healthy controls (HCs) using several assays. Initial analyses included VWF:Antigen (VWF:Ag), VWF:Activity (VWF:Ac), Factor VIII (FVIII), and the VWF Antigen/VWF:Activity (VWF:Ag/VWF:Ac) ratio, providing quantitative and qualitative insights. Further specific tests included VWF multimeric analysis and VWF propeptide (VWFpp) levels, complemented by both the custom reverse Ristocetin Induced Platelet Aggregation (RRIPA) assay and the traditional Ristocetin Induced Platelet Aggregation (RIPA) assay. Our findings revealed a loss of high molecular weight multimers (HMWM) with a corresponding increase in intermediate (IMWM) and low molecular weight multimers (LMWM) within the MPN cohort. VWFpp levels were normal, indicating regular VWF release. However, the VWFpp to VWF antigen ratio (VWFpp:VWFAg) was elevated, suggesting a shortened half-life of plasma VWF and reflecting increased clearance. Measurements of maximum aggregation (MA) from both RRIPA and RIPA assays indicated a defect in aggregation; changes in RRIPA were not statistically significant, indicating that normal platelet function might partially compensate for these VWF abnormalities.