Myeloproliferative Neoplasms, Clonal Thrombosis, and Vascular Disease: Can Cardiology Learn from Hematology?

Philadelphia-negative myeloproliferative neoplasms (MPNs), encompassing polycythemia vera, essential thrombocythemia, and primary myelofibrosis, represent a group of chronic clonal hematopoietic disorders characterized by excessive proliferation of myeloid lineages and with a propensity for arterial and venous thrombosis. These disorders provide a unique human model of inflammation-driven, clone-mediated vascular disease with mechanistic insights highly relevant to cardiovascular medicine. The interplay of elevated hematocrit, leukocytosis, activated platelets, neutrophil extracellular traps, endothelial dysfunction, and chronic cytokine elevation creates a multifaceted prothrombotic state. Randomized evidence, such as the CYTO-PV (cytoreductive therapy in polycythemia vera) trial, demonstrates that correcting hematocrit meaningfully reduces major cardiovascular and thrombotic events. Discoveries like Janus Kinase 2 valine-to phenylalanine substitution on position 617-mutated clones, altered platelet biology, and NETosis inform evolving concepts in coronary artery disease, microvascular ischemia, and inflammatory thrombosis. This review synthesizes thrombosis biology in MPNs with actionable implications for cardiologists. Key lessons include the importance of clonal hematopoiesis as a cardiovascular risk factor, the role of inflammation and hematologic dysregulation in accelerating atherothrombosis, and the therapeutic relevance of antiplatelet optimization, hematocrit control, cytoreductive therapy, and anti-inflammatory interventions. The review also outlines diagnostic situations in cardiology where MPNs should be suspected, proposes opportunities for improved risk stratification, and identifies research priorities bridging the 2 specialties.