Chapter 43: Essential Thrombocythemia

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.

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 ...