Thrombosis in myeloproliferative neoplasms: A clinical and pathophysiological perspective

Abstract

Myeloproliferative neoplasms (MPNs) are clonal haematopoietic stem cell disorders characterised by myeloid progenitor proliferation in the bone marrow. Polycythaemia vera (PV), essential thrombocythaemia (ET) and primary myelofibrosis (PMF) are Philadelphia-chromosome negative classic MPNs defined as per the World Health Organization (WHO) 2016 classification and diagnostic criteria. Thrombosis, comprising of both arterial and venous events, is recognised as a leading cause of morbidity and mortality in ET and PV. Several patient and disease-specific characteristics have been shown to correlate with increased thrombotic risk in MPN. Clinical risk factors include age, history of previous thrombosis, cardiovascular comorbidities, and mutation status. The pathobiology of thrombosis in MPN is multifactorial and results from a complex interplay between blood cells, endothelial cells, coagulation system and inflammatory mediators. Platelets, leukocytes, and erythrocytes exist in a hyperactive and proadhesive state. Furthermore, endothelial dysfunction, haemostatic elements and cytokine dysregulation are implicated in thrombogenesis. MPN driver mutations enhance the thrombotic environment, while the chronic inflammatory state further promotes clonal expansion. Much of the current treatment paradigms for MPN focus on primary prevention of thrombosis with antiplatelet agents and cytoreduction. There is a lack of high-quality data informing the optimal approach to secondary prevention of recurrent thrombosis in MPN. Further advances in the characterisation of the cellular and molecular mechanisms underlying thrombotic tendency in MPN are necessary in order to improve personalised risk prediction/stratification and treatment strategies. This review outlines the incidence, nature, and risk factors for thrombosis in MPN, gives an overview of the mechanisms underlying hypercoagulability and discusses prevention and treatment considerations.