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Essential thrombocytosis (ET, essential thrombocythemia) is a rare chronic blood disorder characterized by the overproduction of platelets by megakaryocytes (the precursor cell for platelets) in the absence of an alternative cause. In some cases this disorder may be progressive, and occasionally evolves into acute leukemia or myelofibrosis.
Epidemiology
Essential thrombocytosis is diagnosed at a rate of about 2 to 3 per 100,000 individuals and usually affects middle aged to elderly individuals, although it can affect children and young adults.
Pathophysiology
The pathologic basis for this disease is unknown. However, essential thrombosis resembles polycythemia vera in that cells of the megakaryocytic series are more sensitive to growth factors. Platelets derived from the abnormal megakaryocytes do not function properly, which contributes to the clinical features of bleeding and thrombosis.
In 2005, a mutation in the JAK2 kinase (V617F) was found by multiple research groups Baxter EJ et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005;365:1054-61. PMID 15781101 Levine RL et al. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell. 2005;7:387-97. PMID 15837627 to be associated with essential thrombocytosis in around 30% of cases. JAK2 is a member of the Janus kinase family. This mutation may be helpful in making a diagnosis or as a target for future therapy.
Clinical features
The major symptoms are bleeding and thrombosis. Other symptoms include epistaxis (nosebleeds) and bleeding from gums and gastrointestinal tract. One characteristic symptom is throbbing and burning of the hands and feet due to the occlusion of small arterioles by platelets (erythromelalgia). An enlarged spleen (splenomegaly) may be found on examination.
Diagnostic criteria
The diagnosis of essential thrombocytosis requires the presence of a persistent thrombocytosis of greater than 600 x109/L in the absence of an alternative cause.
The following revised diagnostic criteria for essential thrombocytosis were proposed in 2005 Campbell PJ, Green AR. Management of Polycythemia Vera and Essential Thrombocythemia. Hematology (Am Soc Hematol Educ Program). 2005;:201-8. PMID 16304381. The diagnosis requires the presence of both A criteria together with B3 to B6, or of criterion A1 together with B1 to B6.
- A1. Platelet count > 600 x 109/L for at least 2 months
- A2. Acquired V617F JAK2 mutation present
- B1. No cause for a reactive thrombocytosis
- normal inflammatory indices
- B2. No evidence of iron deficiency
- stainable iron in the bone marrow or normal red cell mean corpuscular volume
- B3. No evidence of polycythemia vera
- hematocrit < midpoint of normal range or normal red cell mass in presence of normal iron stores
- B4. No evidence of chronic myeloid leukemia
- no Philadelphia chromosome or bcr-abl gene rearrangement
- B5. No evidence of myelofibrosis
- no collagen fibrosis and ≤ grade 2 reticulin fibrosis (using 0–4 scale)
- B6. No evidence of a myelodysplastic syndrome
- no significant dysplasia
- no cytogenetic abnormalities suggestive of myelodysplasia
Treatment
Not all patients will require treatment at presentation. In those who are at increased risk of thrombosis or bleeding (older age, prior history of bleeding or thrombosis, or very high platelet count), reduction of the platelet count to the normal range can be achieved using hydroxycarbamide, interferon-α or anagrelide. Low-dose aspirin is widely used to reduce the risk of thrombosis, but there may be an increased risk of bleeding if aspirin is initiated whilst the platelet count is very high.
The PT1 study Harrison CN et al. Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Engl J Med. 2005;7:33-45. PMID 16000354. compared hydroxycarbamide to anagrelide as initial therapy for essential thrombocytosis. Hydroxycarbamide was superior, with lower risk of arterial thrombosis, lower risk of severe bleeding and lower risk of transformation to myelofibrosis (although the rate of venous thrombosis was higher with hydroxycarbamide than with anagrelide).
In rare cases where patients have life-threatening complications, the platelet count can be reduced rapidly using platelet apheresis (a procedure that removes platelets from the blood directly).
Prognosis
Essential thrombocytosis is a slowly progressive disorder with long asymptomatic periods punctuated by thrombotic or hemorrhagic events. The median survival of patients with this disorder is 12 to 15 years, and may be much longer in younger patients. In the PT1 trial, the five-year risk of progression to myelofibrosis was 2% (in the hydroxycarbamide arm) and the five-year risk of progression to acute myeloid leukaemia approximately 1% .
References
External links
"Essential thrombocytosis"