The state of the hemostasis system in patients with myeloproliferative neoplasm: primary results

Introduction. Essential thrombocythemia (ET) is a type of clonal myeloproliferative neoplasm, which is characterized by uncontrolled proliferation of megakaryocytes. It is associated with an increased number of large and giant megakaryocytes in the bone marrow, leading to thrombocytosis and a high risk of both thrombosis and bleeding. Unlike in adults, pediatric patients with ET often do not experience any clinical manifestations of the disease. However, based on data from adult studies, it is possible that ET and polycythemia vera in children can also lead to both thrombotic and hemorrhagic complications. Changes in the hemostatic system are an important factor that can contribute to these risks.

The aim of this study was to evaluate the state of blood coagulation system in children with thrombocytosis and erythrocytosis using standard coagulation tests, aggregometry, global hemostasis assays, levels of von Willebrand factor antigen (vWF:Ag) and activity and markers of endothelial dysfunction.

Materials and methods. Activated partial thromboplastin time, prothrombin time, thrombin time, fibrinogen, antithrombin III, D-dimer, vWF:Ag and activity RCo of von Willebrand factor, platelet aggregation with adenosine diphosphate (ADP), collagen, ristocetin, thromboelastography and thrombodynamics, endothelin-1 and thrombomodulin levels. The concentration of procoagulant micropartocles derived from the patients' plasma was estimated by flow cytometry. 59 patients diagnosed with ET were enrolled in this study. 13 children with secondary thrombocytosis and 23 with erythrocytosis were enrolled as the control groups.

Results. The results of routine coagulation tests, as well as measurements of antithrombin III activity, D-dimer levels, vWF:Ag, thrombomodulin and endothelin-1, were within the normal range in most patients. The decrease in platelet aggregation was observed after stimulation with ADP in 29 % of patients, with collagen in 37 %, and with ristocetin in 47 %. A statistically significant correlation was found between the decrease in platelet aggregation and the increase in platelet counts. Increased aggregation was seen with ADP and collagen in only 11 and 18 % of patients, respectively, which may indicate a potential prothrombotic tendency and microcirculatory abnormalities in patients with ET.

Acquired von Willebrand syndrome was present in 54 % of patients. Analysis showed that among patients with extreme thrombocytosis (> 1500 × 109/L), all had acquired von Willebrand disease. In addition, in patients with extreme thrombocytosis, there was an increase in parameters of thromboelastography, such as angle α and maximum amplitude, as well as clot growth rates in the thrombodynamics test.

Correlation analysis showed significant dependences (p < 0.05) between the parameters of thromboelastography and thromobodynamics on both platelet count and number of procoagulant microvesicles.

Conclusions. Despite the differences in clinical manifestations in children with ET, a close correlation has been identified between increased platelet counts and changes in their aggregation function, as well as, between increased platelet counts and changes in global hemostasis assays. All patients with hemorrhagic symptoms had laboratory signs of acquired von Willebrand syndrome.

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