Thrombotic and Bleeding Complications in Myeloproliferative Neoplasms: An Integrated Clinical Perspective

Abstract: Myeloproliferative neoplasms (MPNs) are clonal hematopoietic disorders characterized by elevated thrombotic and bleeding risk, and optimal risk stratification and management remain challenging. This review summarizes current evidence on the thrombotic complications in MPNs, including venous events (i.e., deep vein thrombosis, pulmonary embolism, and unusual site thrombosis), and arterial events (ischemic stroke, myocardial infarction, and peripheral arterial thrombosis), and the increased bleeding risk in these diseases. Mechanistically, JAK2-driven clonal hematopoiesis, elevated hematocrit, leukocytosis, platelet activation, endothelial dysfunction, and chronic inflammation interact to promote a pro-thrombotic state; conversely, extreme thrombocytosis, acquired von Willebrand syndrome, and anticoagulant/antiplatelet therapy contribute to bleeding risk. Clinically, thrombosis may precede MPN diagnosis, especially in unusual sites, and treatment should balance the risk of recurrent thrombosis against the risk of hemorrhagic complications. Antithrombotic strategies include low-dose aspirin, vitamin K antagonists, and direct oral anticoagulants, while cytoreductive therapy (hydroxyurea, anagrelide, interferon, and JAK inhibitors) is central for disease control as well as vascular risk reduction. Despite therapy, recurrence of thrombotic events and major bleeding persists, highlighting the need for optimized risk models and alternative therapeutic targets. Future research may focus on integrating molecular biomarkers, inflammation metrics, and vascular-specific endpoints to direct personalized preventive strategies.