What is the best course of management for a patient with chronically elevated platelet count (thrombocytosis), migraines, brain fog, and peripheral neuropathy, with a history of menorrhagia, iron deficient anemia, and current hormone replacement therapy (HRT)?

Management of Chronic Thrombocytosis in a Young Adult with Neurologic Symptoms

Critical First Step: Rule Out Myeloproliferative Neoplasm

This patient requires immediate hematology referral to exclude essential thrombocythemia (ET), a myeloproliferative neoplasm that can cause the exact constellation of symptoms described—chronic thrombocytosis with neurologic manifestations including headaches, paresthesias, visual disturbances, and peripheral neuropathy. 1

Why This Matters for Morbidity and Mortality

• Essential thrombocythemia causes paradoxical thrombosis AND bleeding, explaining both the easy bruising and potential microvascular ischemic symptoms 2
• Neurologic complications occur in 64% of ET patients (21 of 33 patients in prospective study), including headache, paresthesias, visual disturbances, and posterior/anterior cerebral ischemia 1
• Untreated ET carries significant risk of stroke and thrombotic events, particularly in younger patients with platelet counts in the 450-600 range 1

Diagnostic Algorithm

Immediate Workup Required:

1. JAK2 V617F mutation testing - present in ~50-60% of ET cases 2
2. CALR and MPL mutation testing if JAK2 negative 2
3. Peripheral blood smear review - look for large platelets, platelet anisocytosis, megakaryocyte fragments 2
4. Bone marrow biopsy with cytogenetics - essential for definitive ET diagnosis, shows increased megakaryocytes with hyperlobulated nuclei 2
5. Exclude secondary causes: CRP, ferritin (though iron deficiency is resolved), tissue inflammation markers 2

Key Diagnostic Pitfall:

The resolved iron deficiency anemia and menorrhagia could have masked underlying ET, as reactive thrombocytosis from iron deficiency typically resolves once iron stores normalize. The persistence of thrombocytosis 7 years later strongly suggests primary thrombocythemia rather than reactive thrombocytosis 2

Treatment Strategy Based on Diagnosis

If Essential Thrombocythemia is Confirmed:

Immediate initiation of low-dose aspirin (50-100 mg daily) is indicated for neurologic symptom control, as these symptoms represent microvascular platelet-mediated ischemia 1, 3

• Aspirin completely abolishes neurologic and visual symptoms in ET through control of platelet function 3
• All 21 patients with neurologic manifestations responded satisfactorily to treatment in the Polycythemia Vera Study Group prospective study 1
• Keep aspirin dose as low as possible (50-100 mg) to minimize bleeding risk while maintaining efficacy 4

Cytoreductive Therapy Indications:

This 26-year-old patient likely requires cytoreductive therapy in addition to aspirin based on:

• Symptomatic disease (neurologic symptoms, easy bruising) 1
• Platelet count consistently >450 × 10⁹/L 5
• History of migraines with neurologic symptoms suggests microvascular complications 3

First-line cytoreductive agent: Hydroxyurea 1

• Target platelet count: <400 × 10⁹/L
• Alternative: Anagrelide is FDA-approved specifically for thrombocythemia secondary to myeloproliferative neoplasms to reduce platelet count and thrombosis risk 5

Monitoring for Treatment Response:

• Neurologic symptoms should resolve within days to weeks of aspirin initiation 3
• Platelet counts should be monitored every 2-4 weeks during cytoreduction 1
• If symptoms persist despite aspirin, consider plateletpheresis for acute symptom control while awaiting cytoreductive effect 1

Critical Management Considerations

Bleeding Risk Assessment:

• Easy bruising with thrombocytosis is pathognomonic for qualitative platelet dysfunction seen in ET 2
• Do NOT use dual antiplatelet therapy (aspirin + clopidogrel) as this increases bleeding without improving efficacy 4
• Platelet counts >1000 × 10⁹/L carry acquired von Willebrand syndrome risk, though this patient's counts are below that threshold 2

Neurologic Symptom Pattern Recognition:

The described symptoms (migraines, brain fog, facial twitching, peripheral neuropathy, tinnitus) are classic for ET microvascular complications 1, 3:

• Brief attacks of sudden cerebral dysfunction (brain fog, twitching)
• Dull, throbbing headache lasting hours (migraines)
• Visual/auditory symptoms (tinnitus)
• Paresthesias (peripheral neuropathy)

These are NOT typical migraine or primary neurologic disorders but rather represent shear rate-induced platelet aggregation causing transient microvascular occlusion 3

If Myeloproliferative Neoplasm is Excluded:

Observation only is appropriate if comprehensive workup excludes ET and other myeloproliferative disorders 2:

• Reactive thrombocytosis (platelet count 450-600) without symptoms requires no treatment
• Continue monitoring platelet counts every 6-12 months
• Reassess if counts rise >600 or new symptoms develop

However, Given This Clinical Picture:

The 7-year duration, persistent elevation, and constellation of neurologic symptoms make reactive thrombocytosis highly unlikely 2, 1. This patient's presentation is essentially diagnostic of ET until proven otherwise.