From the Guidelines
In a patient with polycythemia vera on anagrelide who has a severe white blood cell count elevation of 40-50 × 10^9/L during resolving pneumonia, urgent hematology consultation is recommended and hydroxyurea should be considered at a starting dose of 500-1000 mg daily to reduce the white cell count. This marked leukocytosis likely represents a combination of the underlying myeloproliferative neoplasm and an inflammatory response to infection 1. While continuing anagrelide for platelet control, the addition of hydroxyurea is supported by the European LeukemiaNet guidelines, which favor hydroxyurea as first-line therapy for patients with essential thrombocythemia (ET) in need of cytoreduction 1.
Key Considerations
- The patient's severe white blood cell count elevation increases the risk of thrombotic events, particularly in the context of polycythemia vera, which already confers an elevated thrombotic risk 1.
- Hydroxyurea works by inhibiting DNA synthesis in rapidly dividing cells, effectively reducing white cell production in the bone marrow 1.
- Complete blood counts should be monitored twice weekly initially to assess the response to hydroxyurea and adjust the dose as necessary.
- The pneumonia should be treated with appropriate antibiotics if not already completed, to address the underlying inflammatory cause of the leukocytosis.
- If hydroxyurea is contraindicated or ineffective, alternative options such as ruxolitinib or interferon alpha may be considered, though these would require specialist initiation 1.
Management Approach
- Urgent hematology consultation to assess the patient and guide management.
- Continue anagrelide for platelet control.
- Initiate hydroxyurea at a starting dose of 500-1000 mg daily, with dose adjustments based on response.
- Monitor complete blood counts twice weekly initially.
- Treat pneumonia with appropriate antibiotics if necessary.
- Maintain adequate hydration to prevent hyperviscosity complications.
From the Research
Severe Elevation of White Cell Count in Polycythemia Vera
- A severe elevation of white cell count of 40-50 in the setting of resolving pneumonia and a history of polycythemia vera being treated with anagrelide is a complex clinical scenario 2, 3.
- Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by an increased red blood cell mass and increased risk of thrombosis, and is often associated with leukocytosis (49%) and thrombocytosis (53%) 2.
- Anagrelide is used to reduce platelet counts in patients with PV, but its use is limited to situations where patients develop thrombohemorrhagic episodes in the setting of extreme thrombocytosis 3.
- The current goal of therapy in PV is to prevent thrombosis, and periodic phlebotomy, with a hematocrit target of <45%, combined with once- or twice-daily aspirin (81 mg) therapy, is the backbone of treatment in all patients, regardless of risk category 4, 5.
Management of White Cell Count Elevation
- Cytoreductive therapy is reserved for high-risk disease, with first-line drugs of choice being hydroxyurea and pegylated interferon-α, and second-line busulfan and ruxolitinib 4, 5.
- The management of white cell count elevation in PV is crucial to prevent thrombotic complications, and the choice of cytoreductive therapy should be individualized based on patient risk factors and disease characteristics 5.
- The REVEAL study highlights the importance of active management of patients with PV, with appropriate hydroxyurea dose titration to maintain blood count control while monitoring for signs and symptoms of hydroxyurea intolerance 6.
Considerations for Anagrelide Treatment
- Anagrelide is not typically used as a first-line treatment for PV, but may be considered in patients with extreme thrombocytosis or thrombohemorrhagic episodes 3.
- The use of anagrelide in combination with other cytoreductive therapies, such as hydroxyurea, should be carefully monitored to minimize the risk of adverse effects 3, 6.