What is the optimal management of a patient over 60 with polycythemia vera, elevated hematocrit and platelet count, who presents with an acute ischemic or hemorrhagic stroke?

Management of Polycythemia Vera Presenting with Acute Stroke

Immediate Stroke Management

For patients over 60 with polycythemia vera presenting with acute ischemic stroke, initiate aspirin 160-325 mg within 24-48 hours (unless thrombolysis was given), perform urgent phlebotomy to reduce hematocrit below 45%, and start cytoreductive therapy with hydroxyurea once stabilized. 1, 2

Acute Ischemic Stroke Protocol

• Start aspirin 160-325 mg within 24-48 hours of stroke onset to reduce mortality and recurrent stroke risk, avoiding approximately 10 deaths and recurrent strokes per 1,000 patients treated 2
• Do NOT administer aspirin within 24 hours after thrombolytic therapy if rtPA was given, as this increases hemorrhage risk 2
• Aspirin can be given orally, via nasogastric tube, or rectally if swallowing is impaired 2
• For minor stroke (NIHSS <4), consider dual antiplatelet therapy with aspirin + clopidogrel (loading doses: aspirin 160-325 mg + clopidogrel 300-600 mg) within 12-24 hours for 21-30 days only 2

Acute Hemorrhagic Stroke Protocol

• Antiplatelet therapy should be carefully reconsidered in hemorrhagic stroke and only used if there is a strong indication 3
• The European guidelines note insufficient evidence to define clear recommendations for antiplatelet use after intracranial hemorrhage in polycythemia vera patients 3
• Urgent hematocrit reduction through phlebotomy is critical as hyperviscosity contributes to both ischemic and hemorrhagic complications 4, 5

Urgent Hematocrit Management

Perform immediate phlebotomy to achieve hematocrit <45% (or approximately 42% in women) with careful fluid replacement to prevent hypotension, particularly in elderly patients with cardiovascular disease. 1, 6

• The CYTO-PV trial definitively showed increased thrombotic risk at hematocrit levels 45-50%, making strict control below 45% mandatory 1
• Hematocrit levels >44% are associated with progressive increases in vascular occlusive episodes and suboptimal cerebral blood flow occurs at 46-52% 6
• Provide adequate fluid replacement during phlebotomy to prevent dangerous hypotension, especially in elderly patients with cardiovascular disease 1
• Hyperviscosity from elevated hematocrit is the major factor causing both thrombotic and hemorrhagic complications in polycythemia vera 5

Risk Stratification and Long-Term Management

This patient is definitively high-risk (age >60 AND history of thrombosis) and requires cytoreductive therapy in addition to phlebotomy and aspirin. 1, 6

Cytoreductive Therapy Selection

• Hydroxyurea is the first-line cytoreductive agent for patients over 60, starting at 500 mg twice daily (or 2 g/day, 2.5 g/day if body weight >80 kg) 1, 6
• Target response: hematocrit <45% without phlebotomy, platelet count ≤400 × 10⁹/L, and WBC count ≤10 × 10⁹/L 1
• Interferon-α is preferred for younger patients (<40 years) due to its non-leukemogenic profile, but this patient's age makes hydroxyurea appropriate 1, 6

Defining Treatment Failure

Hydroxyurea resistance/intolerance is defined by: 1, 6

• Need for phlebotomy to keep hematocrit <45% after 3 months of at least 2 g/day hydroxyurea
• Uncontrolled myeloproliferation (platelet count >400 × 10⁹/L and WBC count >10 × 10⁹/L) after 3 months
• Failure to reduce massive splenomegaly
• Cytopenia or unacceptable side effects at any dose

If hydroxyurea fails, switch to interferon-α as second-line therapy (non-leukemogenic, achieves up to 80% hematologic response) or consider ruxolitinib 1

Cardiovascular Risk Factor Management

Aggressively manage all modifiable cardiovascular risk factors including hypertension, hyperlipidemia, diabetes, and mandatory smoking cessation. 1, 7

• Blood pressure should be lowered if ≥140/90 mm Hg and treated to target <130/80 mm Hg 3
• RAS blockers, calcium channel blockers, and diuretics are first-line antihypertensive agents for stroke patients 3
• Lipid-lowering treatment is mandatory with LDL-C target <70 mg/dL (1.8 mmol/L) in ischemic stroke 3
• Cardiovascular risk factors negatively affect survival in polycythemia vera and must be addressed 7

Monitoring Strategy

• Monitor hematocrit levels, complete blood count, and assess for new thrombotic or bleeding events every 3-6 months 1
• Evaluate for signs/symptoms of disease progression to myelofibrosis regularly 1
• There is no routine indication to monitor JAK2V617F allele burden except when using interferon-α therapy 1

Critical Pitfalls to Avoid

• Never 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 as it can precipitate hypotension, particularly in elderly patients with cardiovascular disease 1
• Do not use chlorambucil or ³²P as these agents carry significantly increased leukemia risk 1
• Avoid using aspirin as a substitute for intravenous rtPA in eligible acute stroke patients 2
• Do not delay cytoreductive therapy in high-risk patients—phlebotomy and aspirin alone are insufficient for patients over 60 with thrombosis history 1

Special Consideration for Severe Polycythemia

The only potential exception for hemodilution therapy (otherwise not recommended for acute ischemic stroke) is in stroke patients with severe polycythemia, though phlebotomy is the preferred approach 3