The pathobiology of thrombosis, microvascular disease, and hemorrhage in the myeloproliferative neoplasms

Thrombotic, vascular, and bleeding complications are the most common causes of morbidity and mortality in the Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs). In these disorders, circulating red cells, leukocytes, and platelets, as well as some vascular endothelial cells, each have abnormalities that are cell-intrinsic to the MPN driver mutations they harbor (eg, JAK2 V617F). When these cells are activated in the MPNs, their interactions with each other create a highly proadhesive and prothrombotic milieu in the circulation that predisposes patients with MPN to venous, arterial, and microvascular thrombosis and occlusive disease. Bleeding problems in the MPNs are caused by the MPN blood cell-initiated development of acquired von Willebrand disease. The inflammatory state created by MPN stem cells in their microenvironment extends systemically to amplify the clinical thrombotic tendency and, at the same time, preferentially promote further MPN stem cell clonal expansion, thereby generating a vicious cycle that favors a prothrombotic state in these diseases.

Automated summary

Thrombotic, vascular, and bleeding complications are common causes of morbidity and mortality in Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs). Abnormalities in circulating cells in MPNs create a prothrombotic environment, leading to venous, arterial, and microvascular thrombosis. The inflammatory state of MPN stem cells amplifies the clinical thrombotic tendency and promotes further MPN stem cell clonal expansion.