Von Willebrand factor multimer profile and function in children and young adults with essential thrombocythemia

Essential thrombocythemia (ET) is a clonal myeloproliferative disease characterized by the uncontrolled proliferation of megakaryocytes. Hemorrhagic manifestations in ET depend largely on the extent of decrease in von Willebrand factor (vWF) activity that is disproportionate to vWF antigen concentration, which may be associated with an increased loss of the most hemostatically active high molecular weight vWF multimers. The aim of our study was to analyze clinical and laboratory manifestations as well as multimer profile and functional characteristics of vWF in children with ET. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation. Five patients with ET were tested for platelet count, vWF ristocetin cofactor activity (vWF:RCo) and vWF antigen (vWF:Ag), factor VIII binding capacity of vWF (vWF:FVIIIВ) and vWF collagen binding capacity (vWF:СВ). VWF multimer analysis with quantitative assessment of multimers was also performed. All the patients had decreased vWF activity of less than 50%, however vWF antigen levels were within the reference ranges. There was a significant association between thrombocytosis and reduced vWF:RCo (the Pearson coefficient –0.975, р = 0.005) and vWF:CB (the Pearson coefficient –0.916, р = 0.029). None of the patients had any changes in standard coagulation test results or decreased vWF:FVIIIВ. Assessment of vWF multimer distribution revealed a reduction in high-molecular weight vWF multimers. A correlation analysis showed no significant relationship between platelet count, vWF:RCo, vWF:Ag, vWF:CB and the concentration of different vWF multimers. Hemorrhagic syndrome presenting as generalized ecchymosis and petechiae was observed in one patient with vWF:RCo equal to 0. Patients with ET have unique laboratory characteristics that do not appear to correlate with clinical symptoms. The specifics of vWF multimer structure and vWF function characterized by a decrease in high-molecular weight vWF multimers and a significant decrease in vWF:RCo which are disproportionate to a decrease in vWF:CB deserve special attention. VWF:CB can probably serve as one the criteria for assessing the risk of hemorrhagic events.