What is the management of polycythemia (excessive red blood cell count)?

From the Guidelines

Management of polycythemia involves a combination of phlebotomy and medications to reduce blood viscosity and prevent thrombotic complications, with the goal of maintaining hematocrit below 45% in men and 42% in women, as supported by the most recent study 1. The cornerstone of treatment for patients with polycythemia vera is therapeutic phlebotomy, which should be performed initially to remove 450-500 mL of blood every 2-3 days until the target hematocrit is achieved, and then maintenance phlebotomies can be performed every 2-3 months as needed.

• Cytoreductive therapy with hydroxyurea (starting at 500-1000 mg daily) is indicated for high-risk patients (age >60 years, history of thrombosis, or platelet count >1.5 million/μL) 1.
• Low-dose aspirin (81-100 mg daily) is recommended for all patients without contraindications to reduce thrombotic risk, as shown in the ECLAP study 1.
• For secondary polycythemia, treatment focuses on addressing the underlying cause, such as COPD, sleep apnea, or high-altitude exposure.
• Ruxolitinib may be used for patients with symptomatic splenomegaly or constitutional symptoms unresponsive to hydroxyurea.
• Interferon-alpha (pegylated forms preferred) is an alternative for younger patients or those planning pregnancy, as suggested by the European LeukemiaNet recommendations 1. Adequate hydration is essential for all polycythemia patients to reduce blood viscosity.
• Regular monitoring of blood counts, iron status, and symptoms is crucial for optimal management and prevention of complications like thrombosis, bleeding, and disease progression, as outlined in the NCCN guidelines 1. The most recent and highest quality study 1 supports the use of intensive phlebotomy treatment to maintain a target hematocrit below 45%, which has been shown to reduce the risk of cardiovascular events and major thrombotic events.

From the Research

Management of Polycythemia Vera

• The management of polycythemia vera (PV) involves controlling vascular risk factors, therapeutic phlebotomy, and low-dose aspirin in all patients 2.
• Patients at higher risk of thrombosis (aged over 60 years and/or with a history of thrombosis) are offered cytoreductive agents, with hydroxyurea or interferons as the preferred first-line agents 2, 3.
• The JAK1 and JAK2 inhibitor, ruxolitinib, is currently approved for the treatment of patients who are resistant to, or intolerant of, hydroxyurea 2.
• Phlebotomy is used to keep hematocrit below 45% in patients with PV, and aspirin therapy is advised to prevent thrombohemorrhagic complications 3.
• The need for additional phlebotomies during hydroxyurea therapy can identify a subset of patients with increased proliferation of PV and higher risk of thrombosis 4.

Risk of Thrombosis and Hemorrhage

• Hematocrit control below 45% is associated with a lower rate of thrombosis in PV 4.
• The combination of aspirin and anticoagulant therapy is associated with a significantly increased risk of hemorrhage in patients with PV 5.
• Periods of thrombocytosis (>600×10^9/L) are associated with an increased risk of hemorrhage 5.
• The risk of thrombosis is higher in patients with the JAK2 mutation 3.
• Leukemic transformation rates at 10 years are estimated at <1% for essential thrombocythemia and 3% for PV 3.

Treatment Options

• Hydroxyurea is the first-line drug of choice for cytoreductive therapy in both essential thrombocythemia and PV 3.
• Interferon-α and busulfan are second-line drugs of choice for cytoreductive therapy 3.
• Ruxolitinib is not recommended for treatment of PV, unless in the presence of severe and protracted pruritus or marked splenomegaly that is not responding to other drugs 3.