Is combination therapy with anticoagulants and antiplatelets (AntiPlatelet agents) indicated in cases of venous thromboembolism (VTE) in Polycythemia Vera (PV)?

From the Guidelines

In venous thromboembolism (VTE) associated with polycythemia vera (PV), the standard approach is to use anticoagulation alone rather than combining anticoagulants with antiplatelets. Patients should typically receive therapeutic anticoagulation with low molecular weight heparin (such as enoxaparin 1 mg/kg twice daily) initially, followed by direct oral anticoagulants (DOACs) like apixaban (5 mg twice daily) or rivaroxaban (15 mg twice daily for 21 days, then 20 mg daily), or warfarin (target INR 2-3) for at least 3-6 months, as recommended by the American College of Chest Physicians (ACCP) Guidelines 1. Indefinite anticoagulation is often recommended for PV patients with VTE due to their persistent thrombotic risk. Cytoreductive therapy with hydroxyurea or ruxolitinib should be optimized alongside anticoagulation to control blood counts, as suggested in the NCCN guidelines 1. Adding antiplatelet therapy (like aspirin) to anticoagulation generally increases bleeding risk without providing additional thrombosis prevention benefit in the venous system, as noted in the ASH guideline panel 1. However, if the patient has concomitant arterial disease or recurrent VTE despite adequate anticoagulation, low-dose aspirin (81-100 mg daily) might be considered after careful assessment of bleeding risk, as mentioned in the Chest guideline 1. The rationale is that venous thrombosis primarily involves fibrin formation and red cell entrapment, which anticoagulants effectively target, while platelets play a more dominant role in arterial thrombosis. Key considerations in the management of VTE in PV include:

• The use of anticoagulant therapy based on current ACCP Guidelines 1
• The assessment of the need for cytoreductive therapy to maintain hematocrit <45% in patients with PV 1
• The evaluation of the risk of bleeding and thrombosis in patients with PV and VTE 1
• The consideration of the use of low-dose aspirin in patients with concomitant arterial disease or recurrent VTE despite adequate anticoagulation 1

From the Research

Combination of Anticoagulants and Antiplatelets in Venous Thromboembolism in PV

• The use of anticoagulants and antiplatelets in patients with polycythemia vera (PV) and venous thromboembolism (VTE) is a complex issue, with studies suggesting that the combination of these therapies may increase the risk of bleeding 2.
• A prospective, observational study found that the combination of aspirin and anticoagulants was associated with a significantly increased risk of hemorrhage in patients with PV, with an exposure-adjusted rate of all hemorrhages of 6.75 per 100 patient-years 2.
• Another study found that nonvitamin K antagonist oral anticoagulants (NOACs) may be effective and safe as secondary prevention of VTE in patients with myeloproliferative neoplasms, including PV, with a low rate of recurrent thrombotic events and bleeding 3.
• The use of antiplatelet drugs, such as aspirin, in patients with PV has been shown to reduce the risk of thrombotic events, but the evidence is limited and the benefit is not statistically significant 4.
• The decision to combine anticoagulants and antiplatelets in patients with PV and VTE should be made on a case-by-case basis, taking into account the individual patient's risk factors and medical history 5, 6.

Risk Factors and Considerations

• Age and history of thrombosis are important risk factors for thrombosis in patients with PV 6.
• Elevated hematocrit and leukocytosis are also associated with an increased risk of thrombosis in patients with PV 6.
• The use of cytoreductive agents, such as hydroxyurea, may reduce the risk of thrombosis in patients with PV 6.
• The risk of bleeding should be carefully considered when combining anticoagulants and antiplatelets in patients with PV, particularly in those with a history of bleeding or thrombocytosis 2.