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Essential Thrombocythemia Diagnosis and Treatment
- 1. Jude Farraj 1810220 Biology and Biotechnology PhD, Zaid Aburubaiha American University of Madaba Essential Thrombocythemia
- 2. Objectives Define Essential Thrombocythemia. Identify its pathogenic mechanism and diagnostic. Explain the causes, diagnosis and treatment for this disease.
- 3. Introduction A clonal myeloproliferative neoplasms with increased megakaryopoiesis and thrombocytosis. Characterized by thrombocytosis and megakaryocytic hyperplasia of the bone marrow.
- 4. Introduction cont. Can be diagnosed by measuring the platelet count in the blood. Most cases occur in individuals between the ages of 50 and 60 years. Risks of vascular events.
- 5. Causes The primary cause is the overproduction of hematopoietic cells due to the mutation of JAK2, CALR gene. These genes are known as driver mutations due to the role they play in the development of a myeloproliferative neoplasm.
- 6. Symptoms In asymptomatic patients, thrombocytosis is usually an incidental finding on complete blood count. For symptomatic patients, the most common symptoms are migraines, headache, dizziness, various levels of thrombosis and splenomegaly. Fig.1 Splenomegaly Fig.2 Thrombosis
- 7. Diagnosis A complete blood count. A bone marrow biopsy. Genetic testing.
- 8. Peripheral Blood and Bone Marrow Commonly, platelets are present in clusters and tend to accumulate near the thin edge of the blood film. Segmented neutrophils may be increased; basophils are not. Erythrocytes are normocytic and normochromic, unless iron deficiency is present secondary to excessive bleeding. Fig3. Peripheral blood film that exhibits early phase thrombocytosis with variation in platelet diameter and shape.
- 9. Peripheral Blood and Bone Marrow cont. Early-phase bone marrow shows marked megakaryocytic hypercellularity, clustering of megakaryocytes, and increased megakaryocyte diameter with nuclear hyperlobulation and density. Fig4. Bone marrow biopsy specimen in essential thrombocythemia showing marked megakaryocytic hypercellularity.
- 10. Peripheral Blood and Bone Marrow cont. Table1. Common Morphologic Changes in Essential Thrombocythemia
- 11. TreatmentManagement Treatment involves prevention or early alleviation of hemorrhagic or vasoocclusive complications that occur as the platelet count increases. The production of platelets must be reduced. Hydroxyurea therapy may achieve a desired reduction of peripheral platelets without the risk of complications.
- 12. Treatment cont. For patients who develop intolerance or resistance to hydroxyurea, cytoreduction can be achieved with interferon-a in younger patients and busulfan in older patients. Low-dose aspirin is also recommended to prevent thrombosis.
- 13. References Keohane, E. M., Otto, C. N., & Walenga, J. M. (2019). Rodak's Hematology: Clinical Principles and Applications. Elsevier Health Sciences. Ashorobi, D. and Gohari, P., (2020). ‘Essential Thrombocytosis’. StatPearls [Internet]. - Figure 3,4 (1) - Table 1 (1)
- 14. Thank you
Editor's Notes
- Myeloproliferative neoplasms are a group of diseases which the bone marrow produces too many red, white blood cells or platelets. ET is also known as primary thrombocytosis, idiopathic thrombocytosis, and hemorrhagic thrombocythaemia
- Normal platelet count is 150,000 to 450,000 platelets per microliter of blood., in thrombocytosis <450,000 platelets per microliter. This is associated with the presence of Janus kinase 2 (JAK2), Calreticulin (CALR) mutations. JAK2 is a gene that provides instructions for making a protein that promotes the growth and division (proliferation) of cells, the JAK2 V617F occurs in approximately 55% of patients with ET In a second peak it primarily occurs in in women in the childbearing years, approximately 30 years of age while its rare in children. Due to thrombocytosis, there are risks of vascular events such as thrombosis and hemorrhage.
- JAK2 is a non-receptor tyrosine kinase found in the cytoplasm playing a pivotal role in hematopoiesis in which it provides instructions for making a protein that promotes the growth and division (proliferation) of cells, the JAK2 V617F mutation which is an acquired, somatic mutation that aids in the gain of function leading to the activation of intracellular signaling pathways associated with the receptors of hematopoietic cytokines: erythropoietin, thrombopoietin, present in most patients with myeloproliferative neoplasms and occurs in approximately 55% of patients with ET. CALR gene is a gene that provides instructions for making a multi-functional protein called calreticulin that is responsible for the regulation of Ca(2+) homoeostasis. Its mutation is related to an insertions or deletions causing a shift in the amino acid reading frame which leads to the formation of a novel C terminus.
- Splenomegaly is a condition that occurs when your spleen becomes enlarged, it is mild when compared to other myeloproliferative neoplasms. Vascular occlusions are often the result of microvascular thromboses in the digits or thromboses in major arteries and veins. Bleeding occurs most frequently from mucous membranes in the gastrointestinal and upper respiratory tracts. Splenomegaly is observed at presentation in 50% of patients.
- In a complete blood count test the number of platelets must exceed 450,000 platelets per microliter of blood. The bone marrow biopsy should show evidence of increased proliferation of the megakaryocytic cell lines with increased numbers of enlarged, matured megakaryocytes. Genetic testing to evaluate for gene mutations whether it’s a mutation in JKA2 or CALR. Also, it helps to determine the phenotype and prognosis of essential thrombocytosis. For instance, a patient with CALR mutations of essential thrombocytosis has a better prognosis.
- The figure includes giantism, agranularity, and pseudopods.
- Special studies reveal increased numbers of smaller and less mature megakaryocytes.
- hemorrhagic or vasoocclusive complications that occur as the platelet count increases as they are the leading causes of morbidity and mortality. The production of platelets must be reduced by suppressing marrow megakaryocyte production with an alkylating agent like hydroxyurea.