Workup for Myeloproliferative Neoplasm (MPN) is Mandatory
This patient requires immediate evaluation for essential thrombocythemia (ET) or early polycythemia vera (PV), given the constellation of chronic thrombocytosis with erythromelalgia, vasomotor symptoms (headaches, facial twitching), and peripheral blood smear showing giant platelet forms. 1
Immediate Diagnostic Workup Required
Obtain JAK2 V617F mutation testing, CALR mutation testing, and MPL mutation testing to establish the diagnosis of ET or PV, as these driver mutations are present in >90% of MPN cases. 1 The presence of occasional giant platelet forms on peripheral smear from one year ago strongly suggests an underlying MPN rather than reactive thrombocytosis. 1
Perform bone marrow aspirate and biopsy to confirm the diagnosis and assess for early myelofibrosis, particularly given the 7+ year duration of thrombocytosis and the complex symptom burden. 1 This is critical before initiating any cytoreductive therapy.
Risk Stratification Determines Management
If JAK2-Positive ET is Confirmed:
This patient falls into the low-risk category (assuming age ≤60 years with no prior thrombosis history), but the presence of JAK2 mutation and severe vasomotor symptoms mandates specific treatment. 1
Initiate low-dose aspirin 81-100 mg twice daily rather than once daily, as patients with ET demonstrate inadequate 24-hour platelet inhibition with once-daily dosing due to high platelet turnover. 2, 3 The twice-daily regimen provides more consistent platelet inhibition (mean difference in platelet aggregation = 228 AU*min, p<0.01) and is safe in ET patients. 3
Use plain (non-enteric coated) aspirin formulation because ET patients display poor responsiveness to enteric-coated preparations. 2
Indications for Cytoreductive Therapy:
Initiate cytoreductive therapy immediately if any of the following are present: 1
- Vasomotor/microvascular disturbances (erythromelalgia, headaches) not responsive to aspirin
- Progressive disease-related symptoms (night sweats, which this patient has)
- Progressive leukocytosis
- Symptomatic or progressive splenomegaly
Hydroxyurea is the first-line cytoreductive agent for patients requiring platelet count reduction, with a target platelet count <400 × 10⁹/L to prevent both thrombotic and microvascular complications. 4
Management of Specific Symptoms
Erythromelalgia (Red Burning Hands/Feet):
This is a pathognomonic microvascular manifestation of thrombocythemia that responds specifically to aspirin therapy. 5, 4 The symptom should resolve within days to weeks of initiating aspirin if the diagnosis is ET. 5 If erythromelalgia persists despite aspirin, add cytoreductive therapy to normalize platelet count. 1, 4
Headaches:
Headaches in ET are disease-related vasomotor symptoms that typically respond to aspirin and platelet count normalization. 6 If headaches persist despite aspirin therapy, this constitutes an indication for cytoreductive therapy per NCCN guidelines. 1
Night Sweats:
Night sweats are progressive disease-related symptoms that mandate initiation of cytoreductive therapy regardless of platelet count. 1
Critical Management Pitfalls to Avoid
Do not withhold aspirin based on platelet count elevation. While thrombocytosis >1,000 × 10⁹/L increases hemorrhage risk, the microvascular symptoms (erythromelalgia, headaches) require aspirin treatment. 1 However, screen for acquired von Willebrand disease before starting aspirin if platelet count is markedly elevated. 1
Do not use aspirin monotherapy if vasomotor symptoms persist after 2-4 weeks of treatment—this indicates need for cytoreductive therapy. 1
Avoid NSAIDs and antiplatelet agents other than aspirin as they increase bleeding risk without providing the specific benefit for ET-related microvascular symptoms. 7
Addressing Comorbid Conditions
The peripheral neuropathy, POTS, and hEDS are likely unrelated to the MPN but may complicate management. Ensure adequate hydration and avoid medications that worsen orthostatic hypotension when treating the MPN. The facial twitching warrants neurological evaluation but is not a typical MPN manifestation.
Monitoring Strategy
Reassess clinically every 3-6 months with complete blood count, symptom assessment, and evaluation for thrombotic/hemorrhagic complications. 1 Repeat bone marrow biopsy if there is clinical suspicion of progression to myelofibrosis (worsening splenomegaly, increasing symptom burden, cytopenias). 1