What is the best management approach for a patient with Polycythemia Vera (a myeloproliferative disorder) experiencing tinnitus (ringing in the ears)?

Management of Tinnitus in Polycythemia Vera

Tinnitus in polycythemia vera is a microvascular symptom caused by hyperviscosity, and the primary treatment is aggressive phlebotomy to maintain hematocrit strictly below 45%, combined with low-dose aspirin (81-100 mg daily) to reduce thrombotic risk and improve microcirculatory symptoms. 1, 2

Understanding the Connection Between PV and Tinnitus

Tinnitus is a recognized microvascular disturbance in polycythemia vera, occurring alongside other hyperviscosity symptoms including headache, light-headedness, transient neurologic or ocular disturbances, atypical chest discomfort, and paresthesias. 2 These symptoms result from increased blood viscosity and impaired microcirculation due to elevated red blood cell mass. 1, 3

Primary Treatment Strategy

Phlebotomy as First-Line Therapy

• Maintain hematocrit strictly below 45% through therapeutic phlebotomy, as the CYTO-PV study definitively demonstrated that hematocrit levels above 45% are associated with progressive increases in vascular occlusive episodes and suboptimal cerebral blood flow. 1, 2

• Consider lower hematocrit targets of approximately 42% for women due to physiological differences in baseline hematocrit values. 1

• Perform phlebotomy with careful fluid replacement to prevent hypotension or fluid overload, particularly in patients with cardiovascular disease. 1

• Suboptimal cerebral blood flow occurs at hematocrit values between 46-52%, which directly contributes to neurologic symptoms including tinnitus. 2

Universal Aspirin Therapy

• Administer low-dose aspirin (81-100 mg daily) to all patients without contraindications, as this significantly reduces cardiovascular death, non-fatal myocardial infarction, stroke, and venous thromboembolism. 1, 2

• Aspirin is particularly effective for platelet-mediated microvascular symptoms in PV. 1

• Low-dose aspirin (40-100 mg) does not increase bleeding risk. 1

Risk Stratification and Cytoreductive Therapy

Determine Risk Category

• High-risk patients are defined as age ≥60 years and/or history of thrombosis. 1, 2

• Low-risk patients are defined as age <60 years with no history of thrombosis. 1, 2

When to Add Cytoreductive Therapy

For patients with persistent tinnitus despite adequate phlebotomy and aspirin, or for high-risk patients, cytoreductive therapy should be considered:

• Hydroxyurea is the first-line cytoreductive agent (Level II, A evidence), dosed at 2 g/day (2.5 g/day if body weight >80 kg). 1

• Interferon-α is preferred for younger patients (<40 years), women of childbearing age, and pregnant patients, achieving up to 80% hematologic response rate and being non-leukemogenic. 1, 2

• Interferon-α can reduce the JAK2V617F allelic burden and may be particularly effective for refractory symptoms. 1

Monitoring Strategy

• Monitor hematocrit levels every 3-6 months to maintain target values below 45%. 1

• Assess for resolution of microvascular symptoms including tinnitus at each visit. 1

• Evaluate for new thrombotic or bleeding events regularly. 1

Additional Considerations

Cardiovascular Risk Factor Management

• Aggressively manage all modifiable cardiovascular risk factors including hypertension, hyperlipidemia, diabetes, and provide mandatory smoking cessation counseling. 1

• These interventions complement the primary treatment of hyperviscosity and further reduce thrombotic risk. 1

When Tinnitus Persists Despite Optimal PV Management

If tinnitus persists despite achieving hematocrit <45% and adequate aspirin therapy, consider alternative causes of tinnitus unrelated to PV:

• Obtain a comprehensive audiologic examination to identify hearing loss or other otologic causes. 4

• Imaging studies should not be obtained unless tinnitus localizes to one ear, is pulsatile, or is associated with focal neurological abnormalities or asymmetric hearing loss. 4

• For persistent bothersome tinnitus after PV is controlled, consider sound therapy or cognitive-behavioral therapy. 4

Critical Pitfalls to Avoid

• Do not accept hematocrit targets of 45-50%, as the CYTO-PV trial definitively showed increased thrombotic risk at these levels. 1

• Avoid inadequate fluid replacement during phlebotomy, which can precipitate hypotension, particularly in elderly patients with cardiovascular disease. 1

• Do not neglect cardiovascular risk factors, as failure to address modifiable vascular risk factors like smoking can worsen outcomes. 2

• Overzealous phlebotomy can increase stroke risk in certain conditions; maintain hematocrit at appropriate target levels. 2