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ET is a chronic state of thrombocytosis that is neither reactive nor related to CML, MMM, PV, or MDS.
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PATHOGENESIS
Serum thrombopoietin levels are elevated or normal despite a high PLT count.
This may be secondary to decreased clearance because of reduced TPO-receptor expression in platelets & megakaryocytes (c-Mpl).
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DIAGNOSIS
Persistent thrombocytosis
Patient not s/p splenectomy
normal ferritin & C-reactive protein (no reactive processes)
Bone marrow excludes MDS, AMM, CML, etc
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CLINICAL FEATURES
1. 25% are asymptomatic at presentation
2. Vasomotor symptoms that includes headaches, transient ocular symptoms, transient neurological symptoms, erythromelalgias, distal paresthesias
3. Thrombosis: arterial or venous including CAD, CVA, PE, DVT, hepatic or portal vein thrombosis, digital ischemia.
4. Bleeding
5. Leukemic conversion in <5%
6. Spontaneous early term abortion up to 45% of the pregnancies in ET.
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PROGNOSTIC FACTORS
Age & history of thrombosis are predictors of future thrombotic events
Note that the degree of thrombocytosis or platelet function abnormalities are not predictors of thrombosis.
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TREATMENT
Note that treatment of patients with ET remains contraversial. Most physicians have favored treating ALL SYMPTOMATIC patients or patients with PLT>1-1.5 million/uL.
Vasomotor symptoms
Aspirin is effective at reducing symptoms of microvascular occlusion in ET. a single dose of ASA can relieve symptoms of erythromelalgia for a few days. Daily ASA also relieves cerebrovascular symptoms.
---take ASA 75-100 mg po QD
Thrombosis
---Hydroxyurea has been shown to reduce the risk of thrombosis in high risk patients from 24% to 4%! Also can try to maintain PLT<400,000.
Lowering Platelet count:
1. Hydroxyurea 15-30 mg/kg/day (rapid onset of action, control of thrmobocytosis in 4-6 weeks)
2. Anagrelide 0.5 mg Qid
This drug appears to work by decreasing megakaryocyte maturation. It has little effect on WBC but can lower RBC in 30% of patients. Need to watch for cardiovascular side effects including CHF & water retention. other side effects include headaches, nausea, or diarrhes.
3. Alpha-interferon 21-35 million units SQ Qweek X 4 weeks then maintenance dose 3 MU QD or 3x/week to keep PLT<600,000.
4. Pipobroman
Europe only
5. Plateletphereis:
For symptomatic patients who need emergent lowering of their PLT count. It should be combined with hydroxyurea i.e. 1.5-3.0 grams QD
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