Effect of thrombopoietin receptor agonists on coagulation and fibrinolysis in patients with immune thrombocytopenia

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by low platelet count and increased bleeding risk. Treatment with thrombopoietin receptor agonists (TPO-RAs) is effective in increasing platelet count, however, an increase in thrombotic risk has been reported. Increased thrombotic risk has also been seen in ITP patients without TPO-RA treatment. The aims of the thesis were to investigate the presence of a procoagulant state in ITP patients and evaluate the influence of TPO-RA treatment on this state by measuring various markers including markers of coagulation activation and fibrinolysis, platelet and endothelial cell activation, and neutrophil extracellular trap (NET) formation. We also assessed the procoagulant activity of the microvesicles (MVs) and measured thrombin generation. ITP patients had increased coagulation activation and impaired fibrinolysis, increased endothelial cell activation and NET formation, all of which can contribute to a procoagulant state. TPO-RA treatment was associated with increased soluble P-selectin indicating increased platelet activation, increased phospholipid-dependent procoagulant activity of microvesicles and further impairment of fibrinolysis. Overall, ITP patients have a procoagulant state and the initiation of TPO-RA treatment may lead to a more hypercoagulable state and thus increased thrombotic risk