Prevention of recurrent thromboembolism in myeloproliferative neoplasms: review of literature and focus on direct oral anticoagulants

ABSTRACT

Myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (MF) are stem cell clonal neoplasms characterized by expansion of late myeloid cells. Thrombosis risk is elevated in MPNs and contributes significantly to morbidity and mortality. Current consensus guidelines make no specific recommendations regarding anticoagulant choice for the treatment of venous thromboembolism (VTE) in MPNs, with most evidence supporting the use of vitamin K antagonists (VKAs) for secondary prophylaxis. However, direct oral anticoagulants (DOACs) are now increasingly being used, although with limited data on safety and efficacy in MPNs specifically. The widespread adoption of DOACs is based on new, high-quality evidence demonstrating safety and efficacy of DOAC treatment for cancer-associated VTE. However, these studies include few if any MPN patients, and MPNs have disease-specific considerations that may elevate thrombosis and bleeding risk. The purpose of this review is to discuss evidence behind current treatment recommendations for thrombosis in MPNs, with special attention to the use of DOACs.

KEYWORDS:

• Myeloproliferative neoplasm
• direct oral anticoagulants
• polycythemia vera
• essential thrombocythemia
• thrombosis

Learning points

• Both venous and arterial thrombosis contributes significantly to morbidity and mortality in patients with MPN. MPN patients are at higher risk for unusual thrombosis sites, especially splanchnic vein thrombosis.

• Mechanisms for increased thrombotic rates include quantitative abnormalities in cell counts leading to elevated blood viscosity and shear stress on vessel walls, as well as qualitative abnormalities in hematopoietic and endothelial cells.

• Previous thrombosis, the presence and allele burden of JAK2 V617F mutation, and older age are the most significant risk factors for subsequent thrombosis in MPN patients.

• Consensus guidelines make no recommendations for the type of anticoagulant used to treat thrombosis in MPNs, although most data are available for Vitamin K antagonists (VKAs). DOACs are recommended on a case-by-case basis.

• Although current studies are limited to smaller retrospective analyses, overall rates of bleeding and re-thrombosis are comparable between DOACs and VKAs in MPNs. Clinicians may consider use of DOACs after weighing patient-specific bleeding and thrombosis risk factors.

Self-assessment questions

Maintaining a hematocrit <45% is associated with reduced thrombosis in polycythemia vera patients. (True)

The presence of a JAK2 V617F mutation increases thrombotic risk in essential thrombocythemia. (True)

Randomized studies of direct oral anticoagulants compared to low molecular weight heparin in cancer patients have generally shown decreased thrombosis and bleeding rates. (False)

Consensus guidelines recommend low molecular weight heparin in the treatment of thrombosis for myeloproliferative neoplasms. (False)

Aspirin in combination with therapeutic anticoagulation is associated with increased bleeding in myeloproliferative neoplasm patients. (True)

Acknowledgments

None stated

Declaration of financial/other relationships

The contents of the paper and the opinions expressed within are those of the authors, and it was the decision of the authors to submit the manuscript for publication.

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Declaration of interest

No potential conflict of interest was reported by the authors.

Additional information

Funding

No funding was received to produce this article