Qualitative and quantitative modifications of von Willebrand factor in patients with essential thrombocythemia and controlled platelet count

Summary Background Essential thrombocythemia ( ET ) is characterized by increased platelets and prevalent thrombosis. An acquired von Willebrand factor ( VWF ) disease has been hypothesized and inconsistently associated with extreme thrombocytosis or rare bleeding in ET . Whether VWF is modified in ET patients with controlled platelet count remains unclear. Objectives We studied different VWF ‐ and platelet‐associated parameters in ET patients treated according to current recommendations. Patients/Methods Sixty‐nine ET patients ( M  = 29; median age, 62 [48–70] years; platelets, 432 [337–620] × 10 3  μL −1 ), 69 matched controls and 10 subjects with reactive thrombocytosis ( RT ) were studied. VWF :antigen (Ag), activity (act), electrophoretic patterns, VWF :propeptide, plasma glycocalycin ( GC ), glycoproteinV (GpV), ADAMTS ‐13, elastase, C‐reactive protein and serum thromboxane ( TX )B 2 were measured. Results In ET patients, VWF :Ag was increased by 31 ± 13% vs. controls ( P  < 0.01), without dependence of blood groups, while VWF :act was reduced by 21 ± 12% vs. controls and by 50 ± 24% vs. RT ( P  < 0.01). The VWF :act/ VWF :Ag ratios in ET were reduced by 35 ± 17% vs. controls and RT patients ( P  < 0.001) and significantly associated with: immature or total platelet counts, GC , GpV and TXB 2 . In multivariable analysis, only GC inversely predicted ET patients’ VWF :act/ VWF :Ag ratios (β = −0.42, P  = 0.01). By electrophoresis analyses, high‐molecular‐weight VWF multimers were variably reduced with atypical cleavage bands in ET only. VWF :propeptide, ADAMTS ‐13 and elastase levels were normal in ET patients. Platelet‐associated ADAM ‐10 and ADAM ‐17 hydrolyzed VWF m in vitro , showing patterns similar to those in ET samples. Conclusions In ET patients with controlled platelet counts, the VWF :act/ VWF :Ag ratio is decreased and predicted by GC , a product of platelet activation. ADAM ‐10 and/or ADAM ‐17 might be involved. In vivo platelet activation, which characterizes ET , might contribute to disease‐specific VWF alterations.