The proposed revised World Health Organization criteria for the diagnosis of essential thrombocythemia requires the following criteria.
- Sustained platelet count of at least 450 × 109/L.
- Bone marrow biopsy showing predominant proliferation of enlarged mature megakaryocytes; no significant increase of granulocytic or erythroid precursors. This finding distinguishes essential thrombocythemia from another entity with thrombocytosis, namely prefibrotic primary myelofibrosis, which is identified by increased granulocytic or erythroid precursors, atypical megakaryocytes, and increased bone marrow cellularity. Patients with prefibrotic primary myelofibrosis have a worse survival than patients with essential thrombocythemia because of an increased progression to myelofibrosis and increased progression to acute myelogenous leukemia.[2,3]
- Not meeting criteria for polycythemia vera (p. vera), primary myelofibrosis, chronic myelogenous leukemia, myelodysplastic syndrome, or other myeloid neoplasm.
- Demonstration of JAK2 V617F mutation or MPL exon 10 mutation. In the absence of a clonal marker, there must be no evidence for reactive thrombocytosis. In particular, with a decreased serum ferritin, there must be no increase in hemoglobin level to p. vera range with iron replacement therapy. In the presence of a JAK2 or MPL mutation and exclusion of other myeloproliferative or myelodysplastic features, a bone marrow aspirate/biopsy may not be mandatory for a diagnosis.
Patients older than 60 years or those with a prior thrombotic episode or with leukocytosis have as much as a 25% chance of developing cerebral, cardiac, or peripheral arterial thromboses and, less often, a chance of developing a pulmonary embolism or deep venous thrombosis.[2,6,7] Similar to the other myeloproliferative syndromes, conversion to acute leukemia is found in a small percentage of patients (<10%) with long-term follow-up.
There is no staging system for this disease.
Untreated essential thrombocythemia means that a patient is newly diagnosed and has had no prior treatment except supportive care.Treatment Overview
Controversy is considerable regarding whether asymptomatic patients with essential thrombocythemia require treatment. A randomized trial of patients with essential thrombocythemia and a high risk of thrombosis compared treatment with hydroxyurea titrated to attain a platelet count below 600,000/mm3 with a control group that received no therapy. Hydroxyurea was found to be effective in preventing thrombotic episodes (4% vs. 24%).[Level of evidence: 1iiDiv] A retrospective analysis of this trial found that antiplatelet drugs had no significant influence on the outcome. Resistance to hydroxyurea is defined as a platelet count of greater than 600,000/mcL after 3 months of at least 2 g per day of hydroxyurea or a platelet count greater than 400,000/µL and a white blood count of less than 2,500/µL or a hemoglobin less than 10 g/dL at any dose of hydroxyurea.
In a case-controlled observational study of 65 low-risk patients (<60 years of age, platelet count <1,500 × 109/L, and no history of thrombosis or hemorrhage) with a median follow-up of 4.1 years, the thrombotic risk of 1.91 cases per 100 patient years and hemorrhagic risk of 1.12 cases per 100 patient years was not increased over the normal controls. A prospective randomized trial of 809 patients compared hydroxyurea plus aspirin versus anagrelide plus aspirin. Although the platelet-lowering effect was equivalent, the anagrelide group had significantly more thrombotic and hemorrhagic events (hazard ratio [HR] = 1.57; P = .03) and more myelofibrosis (HR = 2.92; P = .01). No differences were seen for myelodysplasia or acute leukemia.[Level of evidence: 1iiA] Many clinicians use hydroxyurea or platelet apheresis prior to elective surgery to reduce the platelet count and to prevent postoperative thromboembolism. No prospective or randomized trials document the value of this approach.
Among low-risk patients (defined as age 60 years or younger with no prior thrombotic episodes), a retrospective review of 300 patients showed benefit for antiplatelet agents in reducing venous thrombosis in JAK2-positive cases and in reducing arterial thrombosis in patients with cardiovascular risk factors. Balancing the risks and benefits of aspirin for low-risk patients can be difficult.
- No treatment, unless complications develop, if patients are asymptomatic, younger than 60 years, and have a platelet count of less than 1,500 × 109/L.
- Interferon-alpha [14,15] or pegylated interferon-alpha.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with essential thrombocythemia. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.References
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- Passamonti F, Thiele J, Girodon F, et al.: A prognostic model to predict survival in 867 World Health Organization-defined essential thrombocythemia at diagnosis: a study by the International Working Group on Myelofibrosis Research and Treatment. Blood 120 (6): 1197-201, 2012. [PUBMED Abstract]
- Barbui T, Thiele J, Carobbio A, et al.: Disease characteristics and clinical outcome in young adults with essential thrombocythemia versus early/prefibrotic primary myelofibrosis. Blood 120 (3): 569-71, 2012. [PUBMED Abstract]
- Campbell PJ, Green AR: The myeloproliferative disorders. N Engl J Med 355 (23): 2452-66, 2006. [PUBMED Abstract]
- Harrison CN, Bareford D, Butt N, et al.: Guideline for investigation and management of adults and children presenting with a thrombocytosis. Br J Haematol 149 (3): 352-75, 2010. [PUBMED Abstract]
- Cortelazzo S, Finazzi G, Ruggeri M, et al.: Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N Engl J Med 332 (17): 1132-6, 1995. [PUBMED Abstract]
- Harrison C, Kiladjian JJ, Al-Ali HK, et al.: JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med 366 (9): 787-98, 2012. [PUBMED Abstract]
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- Ruggeri M, Finazzi G, Tosetto A, et al.: No treatment for low-risk thrombocythaemia: results from a prospective study. Br J Haematol 103 (3): 772-7, 1998. [PUBMED Abstract]
- Harrison CN, Campbell PJ, Buck G, et al.: Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Engl J Med 353 (1): 33-45, 2005. [PUBMED Abstract]
- Green A, Campbell P, Buck G: The Medical Research Council PT1 trial in essential thrombocythemia. [Abstract] Blood 104 (11): A-6, 2004.
- Alvarez-Larrán A, Cervantes F, Pereira A, et al.: Observation versus antiplatelet therapy as primary prophylaxis for thrombosis in low-risk essential thrombocythemia. Blood 116 (8): 1205-10; quiz 1387, 2010. [PUBMED Abstract]
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- Sacchi S: The role of alpha-interferon in essential thrombocythaemia, polycythaemia vera and myelofibrosis with myeloid metaplasia (MMM): a concise update. Leuk Lymphoma 19 (1-2): 13-20, 1995. [PUBMED Abstract]
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- Quintás-Cardama A, Kantarjian H, Manshouri T, et al.: Pegylated interferon alfa-2a yields high rates of hematologic and molecular response in patients with advanced essential thrombocythemia and polycythemia vera. J Clin Oncol 27 (32): 5418-24, 2009. [PUBMED Abstract]
- Anagrelide, a therapy for thrombocythemic states: experience in 577 patients. Anagrelide Study Group. Am J Med 92 (1): 69-76, 1992. [PUBMED Abstract]