Abstract
Philadelphia chromosome negative myeloproliferative neoplasms (MPN) are clonal haematopoietic stem cell disorders. Of the MPNs, polycythaemia vera (PV) and essential thrombocythaemia (ET) confer a high thrombotic risk which may be the presenting feature of the disease. Thrombotic complications consist of both arterial and venous events and the presence of the JAK2 V617F mutation is associated with higher risk. Patients presenting with an unprovoked thrombus, particularly at an unusual site, e.g., splanchnic circulation, should be screened for the presence of this mutation. Historically, warfarin has been the only option for oral anticoagulation; however, there is now increasing evidence and practise to use direct oral anticoagulants (DOACs) in cancer. The seminal randomised control trials have demonstrated non-inferiority compared to low molecular weight heparin (LMWH) with a preferable bleeding profile. DOACs are now the first line treatment for atrial fibrillation and venous thromboembolic disease, as recommended by NICE, and therefore there is increasing familiarity with these agents. Furthermore, there are now targeted antidotes available. This paper reviews evidence for efficacy and safety of DOACs in MPN. Whilst no randomised control trials have been performed, several retrospective studies and reviews of registry data have reproducibly demonstrated that, alongside cytoreduction, DOACs represent an effective modality of anticoagulation for treatment of venous thromboembolism in MPN. Furthermore, dosing regimens provide the option for longer term secondary prophylaxis. Use of DOACs in arterial thrombosis is an area for future development and there is already some evidence for utility in peripheral vascular disease.
Highlights
Myeloproliferative neoplasms (MPN) are clonal haematopoietic disorders characterised by myeloid progenitor proliferation in the bone marrow
The mechanism of thrombosis in solid organ malignancies is separate to that observed in MPN; thrombotic potential is correlated with disease control in both cohorts of patients and there is no evidence to suggest the mechanism of action of DOACS would render them less effective in MPN for management of venous thromboembolism
The majority of thromboses were venous in this cohort and the results supported the current data on the safety and efficacy profile of DOACS in MPN, with no significant difference detected in bleeding or recurrent events
Summary
Myeloproliferative neoplasms (MPN) are clonal haematopoietic disorders characterised by myeloid progenitor proliferation in the bone marrow. In the absence of this mutation, CALR, MPL and JAK 2 exon 12 mutations will be present, with only a small proportion characterised as triple negative. Thrombosis comprising both arterial and venous events are a common presenting feature and complication of PV and ET and there is an affiliation between the presence of the JAK2 V617F mutation and an increased thrombotic risk [2]. Molecular analysis of peripheral blood has allowed for rapid and accurate detection of driver mutations. This has transformed the diagnostic potential for MPNs, which is. The seminal randomised control trials that have established the efficacy of DOACs in cancer are HOKUSAIVTE, SELECT-D, ADAM VTE and, most recently, the CARAVAGGIO study [3,4,5,6]
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