Immune-mediated thrombosis in myeloproliferative neoplasms: Pathogenic pathways and clinical relevance.

Abstract

Myeloproliferative neoplasms (MPNs) are clonal hematopoietic neoplasms characterized by a substantial risk of arterial and venous thrombosis, which remains a major cause of disease-related morbidity and mortality. Beyond abnormalities in blood-cell counts and rheology, MPN-associated thrombosis is increasingly recognized as a consequence of chronic thromboinflammation arising from dysregulated interactions among leukocytes, platelets, endothelial cells, inflammatory mediators, and the coagulation system. The canonical driver mutations JAK2, CALR, and MPL converge on constitutive JAK-STAT signaling but are associated with differential thrombotic risk, with JAK2V617F being most consistently linked to an increased risk of thrombosis. Growing evidence suggests that thrombotic complications in MPNs are not solely attributable to clonal expansion and quantitative hematologic abnormalities but also involve qualitative alterations in immune-cell function, platelet activation, endothelial dysfunction, inflammatory signaling, and coagulation. This review summarizes the current mechanistic and clinical evidence linking MPN driver mutations and thromboinflammatory processes to thrombosis and discusses the effects of disease-directed therapies on these interconnected pathways.