What is the management approach for a patient with newly diagnosed polycythemia vera (PV) presenting with an acute ischemic stroke within the tissue plasminogen activator (tPA) thrombolysis period?

Management of Acute Ischemic Stroke in Newly Diagnosed Polycythemia Vera Within the Thrombolysis Window

In a patient with newly diagnosed polycythemia vera presenting with acute ischemic stroke within the tPA window, administer intravenous thrombolysis (rtPA 0.9 mg/kg, maximum 90 mg) following standard protocols if no other contraindications exist, as the presence of PV alone does not constitute an absolute contraindication to thrombolysis. 1, 2

Immediate Assessment and Decision-Making

Critical Initial Steps

• Obtain non-contrast head CT immediately to exclude intracranial hemorrhage and document exact time of symptom onset 1
• Check complete blood count to confirm erythrocytosis (hemoglobin >16.5 g/dL in men or >16.0 g/dL in women) and assess platelet count 3, 4
• Obtain CT angiography to identify large vessel occlusion, as mechanical thrombectomy remains an option regardless of PV diagnosis 1, 5
• Verify blood pressure is controllable to <185/110 mm Hg before initiating thrombolysis 1

Key Laboratory Considerations

• Platelet count is critical: If platelets are ≥1000 × 10⁹/L, there is increased bleeding risk due to acquired von Willebrand disease, which warrants extreme caution 3
• Check coagulation parameters (PT/INR, aPTT) to exclude concurrent anticoagulation 1
• Document hematocrit level, as PV patients typically have elevated values requiring future phlebotomy management 3, 4

Thrombolysis Protocol in PV Patients

Standard rtPA Administration

• Administer rtPA at 0.9 mg/kg (maximum 90 mg total dose) with 10% given as IV bolus over 1 minute and remaining 90% infused over 60 minutes 1, 2
• Initiate treatment as rapidly as possible, as earlier treatment provides greater benefit regardless of underlying hematologic condition 1
• Within 0-3 hours: Strong recommendation for thrombolysis (Grade 1A) 2
• Within 3-4.5 hours: Conditional recommendation for thrombolysis (Grade 2C) 2

Blood Pressure Management During Thrombolysis

• Pre-treatment: If systolic >185 mm Hg or diastolic >110 mm Hg, give labetalol 10-20 mg IV over 1-2 minutes (may repeat once) or nicardipine drip 5 mg/h titrated up by 2.5 mg/h every 5-15 minutes (maximum 15 mg/h) 1
• If blood pressure cannot be reduced below 185/110 mm Hg, do not administer rtPA 1
• During and after treatment: Monitor blood pressure every 15 minutes for 2 hours, then every 30 minutes for 6 hours, then hourly for 16 hours 1

Critical Pitfalls and Contraindications Specific to PV

Absolute Contraindications to Assess

• Extreme thrombocytosis (≥1000 × 10⁹/L): This creates acquired von Willebrand disease and substantially increases bleeding risk beyond the baseline 4-6% symptomatic ICH rate 3, 2
• Concurrent anticoagulation: If the patient is already on anticoagulation for prior thrombotic events (which occur in 16% of PV patients at diagnosis), tPA should not be administered 3, 5
• Recent major bleeding: PV patients have both increased thrombotic AND bleeding risk, particularly with extreme thrombocytosis 3, 4

Relative Considerations

• The baseline symptomatic intracranial hemorrhage rate with rtPA is 6.4% versus 0.6% with placebo, and this may be higher in PV patients with extreme thrombocytosis 2
• PV patients have a 16% rate of arterial thrombosis and 7% rate of venous thrombosis at or before diagnosis, indicating high baseline thrombotic risk that may favor thrombolysis 3

Post-Thrombolysis Management

Immediate Post-rtPA Care

• Insert all necessary IV lines, Foley catheter, and other indwelling tubes BEFORE rtPA administration to minimize trauma and bleeding risk 1
• Monitor for orolingual angioedema (occurs in 1.3-5.1% of rtPA patients), which is more common with ACE inhibitor use 1
• If angioedema develops, administer IV ranitidine, diphenhydramine, and methylprednisolone 1

Antiplatelet Therapy Timing

• Do NOT initiate aspirin during or immediately after rtPA infusion 1
• Initiate aspirin 160-325 mg within 24-48 hours after thrombolysis for patients not receiving anticoagulation 2, 4
• All PV patients require long-term aspirin 81 mg once or twice daily (in absence of contraindications) as part of standard PV management 3, 4, 6

PV-Specific Management Initiated After Acute Phase

• Begin therapeutic phlebotomy to maintain hematocrit <45% once the acute stroke period has stabilized 3, 4, 6
• Risk-stratify the patient: High-risk PV (age >60 years or thrombosis history present) requires cytoreductive therapy with hydroxyurea as first-line 3, 4, 6
• This patient now has a thrombosis history, automatically placing them in the high-risk category requiring cytoreductive therapy 4, 6

Alternative Approach: Mechanical Thrombectomy

When to Prioritize Endovascular Treatment

• If CT angiography demonstrates large vessel occlusion, proceed directly to mechanical thrombectomy consultation 1, 5
• Mechanical thrombectomy can be performed up to 6 hours (or longer with advanced imaging selection) and is not contraindicated by PV 1
• Do not delay rtPA administration to obtain vascular imaging if patient meets clinical criteria for thrombolysis 1
• If rtPA is contraindicated due to extreme thrombocytosis or other factors, mechanical thrombectomy remains a viable option 5

Monitoring for Complications

Hemorrhagic Transformation Surveillance

• Perform neurological assessments every 15 minutes during rtPA infusion and for 2 hours after, then every 30 minutes for 6 hours, then hourly for 16 hours 1
• Obtain urgent head CT if patient develops acute neurological deterioration, severe headache, acute hypertension, nausea, or vomiting 1
• The risk of symptomatic ICH is 1.6% in registry data but 6.4% in clinical trials, and may be higher with extreme thrombocytosis 1, 2

Rethrombosis Risk

• PV patients may have secondary hypercoagulability after thrombolysis, potentially increasing rethrombosis risk 7
• Consider echocardiography if clinical deterioration occurs, as intracardiac thrombus formation has been reported post-rtPA 7