Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content +++ INTRODUCTION ++ The upper limit of a normal platelet count is usually between 350 × 109/L and 450 × 109/L depending on the clinical laboratory and specific method used. Table 43–1 presents the major causes of elevation of the platelet count above the normal limit. Only essential thrombocythemia (ET) is discussed here; familial and reactive thrombocytosis are discussed in Chapter 75, Hereditary and Reactive (Secondary) Thrombocytosis. ++Table Graphic Jump LocationTABLE 43–1MAJOR CAUSES OF THROMBOCYTOSISView Table||Download (.pdf) TABLE 43–1 MAJOR CAUSES OF THROMBOCYTOSIS Clonal thrombocytosis Essential thrombocythemia Polycythemia vera Primary myelofibrosis Chronic myeloid leukemia Refractory anemia with ringed sideroblasts and thrombocytosis 5q-minus syndrome Reactive (secondary) thrombocytosis Transient thrombocytosis Acute blood loss Recovery from thrombocytopenia (rebound thrombocytosis) Acute infection or inflammation Response to exercise Response to drugs (vincristine, epinephrine, all-trans-retinoic acid) Sustained thrombocytosis Iron deficiency Splenectomy or congenital absence of spleen Malignancy Chronic infection or inflammation Hemolytic anemia Familial thrombocytosis Spurious thrombocytosis Cryoglobulinemia Cytoplasmic fragmentation in acute leukemia Red cell fragmentation Bacteremia +++ PATHOPHYSIOLOGY ++ ET is a clonal disorder of multipotential hematopoietic progenitor cells/stem cells. It is a classified as a myeloproliferative neoplasm (MPN) and is related to polycythemia vera, primary myelofibrosis, and chronic myelogenous leukemia (CML; see Chap. 47). However, unlike CML, the other three diseases are not associated with BCR/ABL mutations and thus are generally referred to as Philadelphia chromosome–negative MPNs[0]. Approximately 50% of patients with ET express a mutant form of the Janus 2 signaling kinase (JAK2 V617F) found in several MPNs (eg, polycythemia vera, primary myelofibrosis, rare cases of myelodysplastic syndromes). The mutant allele is almost invariantly found in one copy per cell in patients with ET and leads in vivo to hematopoietic growth factor hypersensitivity, a hallmark of the disease. A very small fraction of patients display other mutations of JAK2. Mutations in JAK2, calreticulin (~35% of patients), or the thrombopoietin receptor MPL gene (~5% of patients) together account for 85% to 90% of the driver mutations in patients with ET. In most instances, the remaining patients without any of these three mutations, who are labeled as having triple-negative ET, display other sematic mutations. Depending on where the patient is in the course of the disease, from 70% to 90% of the marrow and blood cells of patients with ET express the relevant driver mutation. Patients who do not express a mutant form of JAK2 usually display lower hemoglobin concentrations than patients with JAK2 V617F. +++ CLINICAL FEATURES ++ The criteria used for the diagnosis of ET are shown in Table 43–2. ET usually develops between ages 50 and 70. Sex distribution is slightly skewed toward women, especially in younger patients. Because platelet counts are now often done routinely, the disorder is being discovered in younger individuals and in patients who are asymptomatic. Rare familial cases have ... Your Access profile is currently affiliated with '[InstitutionA]' and is in the process of switching affiliations to '[InstitutionB]'. Please click ‘Continue’ to continue the affiliation switch, otherwise click ‘Cancel’ to cancel signing in. Get Free Access Through Your Institution Learn how to see if your library subscribes to McGraw Hill Medical products. Subscribe: Institutional or Individual Sign In Username Error: Please enter User Name Password Error: Please enter Password Forgot Password? Forgot Username? Sign in via OpenAthens Sign in via Shibboleth