How should I manage a patient with hemoglobin 20 g/dL, hematocrit 64%, and a history of cerebral venous sinus thrombosis?

Management of Severe Polycythemia with History of Cerebral Venous Sinus Thrombosis

This patient requires immediate therapeutic phlebotomy to reduce hemoglobin below 20 g/dL and hematocrit below 65%, combined with urgent initiation of anticoagulation therapy to prevent recurrent cerebral venous thrombosis, despite the seemingly paradoxical approach of anticoagulating a patient with extreme erythrocytosis.

Immediate Phlebotomy

Phlebotomy is reasonable in adult patients with hemoglobin >20 mg/dL and hematocrit >65% with hyperviscosity symptoms (headache, lethargy) in the absence of dehydration and iron deficiency 1. This patient meets these criteria with Hb 20 and hematocrit 64%, approaching the threshold where hyperviscosity significantly increases thrombotic risk.

• Remove 250-500 mL of blood initially, with goal hematocrit <45% to minimize thrombosis risk 2
• Ensure adequate hydration before and during phlebotomy to prevent volume depletion 1
• Check iron studies before phlebotomy; iron deficiency is a contraindication 1
• Monitor for symptoms of hyperviscosity including headache, visual changes, dizziness, and focal neurological deficits 3, 2

Anticoagulation for Secondary Prevention

Anticoagulation is the cornerstone of treatment for patients with prior cerebral venous sinus thrombosis, and the presence of polycythemia does not contraindicate this therapy 1.

Initial Anticoagulation Protocol

• Start low-molecular-weight heparin (LMWH) immediately: Enoxaparin 1.0 mg/kg twice daily or 1.5 mg/kg once daily 4, 5
• Alternative: Unfractionated heparin with initial bolus of 5000 IU, followed by continuous infusion adjusted to maintain aPTT at 1.5-2.5 times baseline 4
• Do not delay anticoagulation while awaiting phlebotomy completion 4

Transition to Oral Anticoagulation

• Initiate warfarin early, continuing parenteral anticoagulation for minimum 5 days and until INR ≥2.0 for at least 24 hours 4
• Target INR 2.0-3.0 (goal 2.5) for long-term management 4
• For recurrent venous thrombosis or severe thrombophilia, consider indefinite anticoagulation 4

Duration of Anticoagulation

• Minimum duration: 3 months for all patients with cerebral venous thrombosis 1, 4
• Given history of prior cerebral venous sinus thrombosis, indefinite anticoagulation is reasonable if no reversible cause is identified 4
• If polycythemia is secondary and resolves, consider 6-12 months of anticoagulation 4

Diagnostic Workup

Determine the underlying cause of polycythemia to guide long-term management:

• JAK2 V617F mutation testing to distinguish polycythemia vera from secondary causes 6, 2
• Erythropoietin level (low in PV, normal/high in secondary polycythemia) 2
• Peripheral blood smear examination 3
• Screen for secondary causes: sleep apnea, chronic hypoxia, smoking history, renal pathology 2
• Thrombophilia workup including antiphospholipid antibodies, protein C/S, antithrombin III 1

Cytoreductive Therapy Considerations

If JAK2 mutation is positive (polycythemia vera):

• Hydroxyurea is first-line cytoreductive therapy for high-risk patients (age ≥60 or prior thrombosis) 2
• This patient qualifies as high-risk due to prior cerebral venous thrombosis 2
• Caution: One case report documented cerebral venous thrombosis in a patient on hydroxyurea with elevated hemoglobin 7, suggesting inadequate disease control rather than drug toxicity
• Alternative: Interferon-alpha for younger patients or those intolerant to hydroxyurea 2

Monitoring and Follow-up

• Serial neurological examinations every 2-4 hours during first 24 hours to detect deterioration 4
• Repeat hematocrit after each phlebotomy session until goal <45% achieved 2
• Follow-up CT venography or MR venography at 3-6 months to assess recanalization 4, 5
• Monitor platelet count during anticoagulation to detect heparin-induced thrombocytopenia 4
• Regular CBC monitoring to maintain hematocrit <45% long-term 2

Critical Pitfalls to Avoid

Withholding anticoagulation due to elevated hematocrit is a critical error 4. The thrombotic risk from prior cerebral venous thrombosis outweighs bleeding concerns, and anticoagulation prevents thrombus propagation 1.

• Do not delay anticoagulation for phlebotomy completion 4
• Phlebotomy alone without anticoagulation is insufficient for secondary prevention of cerebral venous thrombosis 4
• Even if hemorrhagic transformation were present on imaging, anticoagulation would still be indicated 4, 5
• Aspirin monotherapy is inadequate for cerebral venous thrombosis prevention 1

Escalation Criteria

Consider endovascular therapy or neurosurgical consultation if:

• Progressive neurological deterioration despite adequate anticoagulation 4
• New focal deficits, worsening consciousness, or seizures develop 4
• Absolute contraindication to anticoagulation emerges 4