Essential thrombocythemia (ET) is a myeloproliferative neoplasm (MPN) characterized by megakaryocyte hyperplasia and thrombocytosis due to a clonal abnormality of a multipotent hematopoietic stem cell.
From the genetic perspective, ET patients harbour mutations in JAK2 (50–60%), CALR (15–30%) and MPL (1–5%) genes.
Platelet survival is normal in ET.
Approximately one-third of patients with ET is asymptomatic at diagnosis.
ET usually occurs with bimodal peaks of between ages 50 and 70 years and a separate peak among young females.
Patients particularly suffer from a combined bleeding and clotting tendency, as well as the general features of myeloproliferative disorders such as anemia, headaches, and malaise.
Bleeding is usually mild and manifests as epistaxis, easy bruising, or GI bleeding. However, thrombosis is a major cause of morbidity and mortality in ET.
Recent studies indicate that an elevated leukocyte count is a major independent risk factor for thromboses.
Erythromelalgia (burning pain in hands and feet, with warmth, erythema, and sometimes digital ischemia) may occur.
Mild splenomegaly occurs in < 50% of patients. Hepatomegaly may rarely occur.
Myelofibrosis is common.
Transformation to Acute Myeloid Leukemia (AML) occurs in 0.6-5% of patients with ET; the risk may be comparable to that of the healthy population.
The diagnosis can be difficult to differentiate from secondary (reactive) thrombocytosis and is partly a diagnosis of exclusion.
Platelets are acute-phase reactants; therefore, they increase in response to various stimuli, including systemic infections, inflammatory conditions, bleeding, and tumors.
*FBC and peripheral blood smear. The platelet count can be >1,000,000/μL but may be as low as 450,000/μL. The peripheral smear may show platelet aggregates, giant platelets, and megakaryocyte fragments.
Essential Thrombocythemia-Blood Film
*Exclusion of causes of secondary thrombocytosis e.g. Chronic inflammatory disorders, hemorrhage, acute infection, iron deficiency, splenectomy, and cancer.
*Cytogenetic studies including Philadelphia chromosome or BCR-ABL assay should be done.
*JAK2 mutation by PCR. The JAK2 V617F mutation occurs in about 50-60% of patients, and if present, helps distinguish ET from other causes of thrombocytosis.
Polycythemia vera is mainly related to JAK2 mutations, whereas a wider mutational spectrum is detected in ET with mutations in JAK2, the thrombopoietin (TPO) receptor (MPL), and the calreticulin (CALR) genes.
Overall, there is general agreement that 10–30% of all ET patients are wild type for JAK2, CALR, and MPL mutations when the molecular analyses are performed with DNA from isolated granulocytes or peripheral blood. This subgroup of patients, called ‘triple-negative’ (TN), has not been extensively studied with regard to the presence of JAK2, CALR and MPL mutations in platelets and RNA from granulocytes.
*Possibly bone marrow aspirate and trephine biopsy. The bone marrow shows increased megakaryocyte numbers and drifts of platelets. Megakaryocytes display a spectrum of morphology with predominant large megakaryocytes with hyperlobated nuclei and abundant cytoplasm. The bone marrow iron is present and reticulin is generally not increased.
To distinguish ET from other myeloproliferative disorders that cause thrombocytosis, the diagnosis of ET requires a normal Hct, MCV, and iron studies to out rule PRV; absence of the Philadelphia chromosome and BCR-ABL translocation to out rule CML; and absence of teardrop-shaped RBCs to out rule idiopathic myelofibrosis, although there may be significant increase in bone marrow fibrosis.
Treatment in patients with ET should be individualized on the basis of risk factors for thrombo- hemorrhagic complications. Risk factors include the following:
- Age 60 years or older.
- History of thrombosis or transient ischemic attack.
- Platelet count >1.5 million/µL.
- Cardiovascular risk factors such as smoking, hypertension, and hypercholesterolemia.
- Markers of hypercoagulability such as factor V Leiden and antiphospholipid antibodies.
Treatment includes the following:
- Observation may be appropriate for low-risk patients (ie, those lacking any of the above risk factors).
- Low dose Aspirin.
- Platelet-lowering drugs (eg, hydroxyurea, anagrelide).
- Rarely plateletpheresis in emergencies to achieve a rapid decrease in platelet counts in the setting of acute thrombosis and/or marked thrombocytosis.
- Rarely cytotoxic agents.
- Rarely interferon.
- Rarely stem cell transplantation.
Thiele J, Kvasnicka HM. The 2008 WHO diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis. Curr Hematol Malig Rep. 2009;4:33-40.
Harrison CN, Bareford D, Butt N, et al; British Committee for Standards in Haematology. Guideline for investigation and management of adults and children presenting with a thrombocytosis. Br J Haematol. 2010;149:352-375.
Fenaux P, Simon M, Caulier MT, et al. Clinical course of essential thrombocythemia in 147 cases. Cancer. 1990;66:549-556.
Toyama K, Karasawa M, Yamane A, Irisawa H, Yokohama A, Saitoh T et al. JAK2-V617F mutation analysis of granulocytes and platelets from patients with chronic myeloproliferative disorders: advantage of studying platelets. Br J Haematol 2007; 139: 64–69.
Cazzola M, Kralovics R. From Janus kinase 2 to calreticulin: the clinically relevant genomic landscape of myeloproliferative neoplasms. Blood 2014; 123: 3714–3719.
Vora AJ, Lilleyman JS. Secondary thrombocytosis. Arch Dis Child. 1993 Jan. 68(1):88-90.
Hoffman R, Benz EJ Jr, Shattil SJ, et al, eds. Primary thrombocythemia. Hematology: Basic Principles and Practice. 3rd ed. Philadelphia, Pa: Churchill Livingstone; 2000. 1188-204.