Pathogenesis of thrombophilia in MPN. The pathogenesis of the acquired thrombophilic state in ET and PV is multifaceted. Mechanisms involved in the pathogenesis of the acquired thrombophilic state associated with these diseases include abnormalities of MPN-clone–derived blood cells (ie, erythrocytes, platelets, and leukocytes), which display prothrombotic features, and abnormalities of normal vascular cells, which become procoagulant in response to inflammatory stimuli. Once activated, neutrophils can also affect the hemostatic system through different pathways. In particular, the release of proteolytic enzymes and of reactive oxygen species can activate or damage platelets and endothelial cells and impair some coagulation proteins. Activated platelets express P-selectin and tissue factor (TF) and release MPs. The increased expression of CD11b on the neutrophil surface allows the adhesion of neutrophils to endothelial cells and platelets and the assembly of coagulation proteases on the neutrophil surface. In addition, abnormalities in red blood cells (RBC), including biochemical changes in the cell membrane and content, may independently impair blood flow also through the formation of RBC aggregates. Furthermore, RBC aggregation facilitates the platelet and leukocyte interaction with the vessel wall.