Pathogenesis of thrombophilia in MPN. The pathogenesis of the acquired thrombophilic state in ET and PV is multifaceted. However, 2 main mechanisms recapitulate the origin of hypercoagulation in these disorders. One relies on the abnormalities of blood cells (ie, platelets, erythrocytes, and leukocytes) arising from the clonal proliferation of hematopoietic progenitor cells, which acquire a prothrombotic phenotype. The other generates from the host inflammatory response to the insult of cytokines and other mediators by the malignant cells. The latter mechanism also contributes to thrombosis in nonmalignant conditions.