Can Novel Insights into the Pathogenesis of Myeloproliferative Neoplasm-Related Thrombosis Inform Novel Treatment Approaches?

Abstract

Despite recent advances in diagnosis and therapy, arterial and venous thrombosis remain a major cause of morbidity and mortality in Philadelphia-negative myeloproliferative neoplasms (MPNs). Preventing and treating arterial and venous thrombosis represent one of the major goals in MPNs. The prothrombotic phenotype of MPNs is the result of a complex interplay between several components. Neutrophils, platelets, red blood cells (RBCs) and endothelial cells assume an activated phenotype in MPNs and undergo morphologic and metabolic changes that render these cells prothrombotic. These changes are in part the result of alterations induced by MPN initiating, driving mutations as well as the effect of extrinsic factors that stem from cell interactions as well as the inflammatory environment and rheological properties that characterize MPNs. In this review, we address current management issues in MPNs and provide an update on recent understanding of the pathogenesis of thrombosis in MPNs. We also address how lessons learned from other thrombo-inflammatory conditions can further inform and improve management of thrombosis in MPNs. Based on the above data and recent discoveries and developments, we discuss potential novel targets and therapeutic approaches to tackle the challenge of thrombosis in MPNs.

Keywords

• myeloproliferative neoplasia
• thrombosis
• pathogenesis
• targeted approaches