48 T. Kühne

5.3.2 Clinical Manifestations

• Headache, weakness, loss of weight, pruritus, dizziness

• Splenomegaly, leukocytosis, and thrombocytosis frequently observed

• Hypercellular bone marrow

• Cell cultures: increased sensitivity to erythropoietin

5.3.3 Management

•Treatment according to symptoms, red cell mass, and arterial oxygen saturation (O2 saturation, O2-saturation curve)

•No standard therapy for pediatric patients

•Hematocrit should be less than 45%, to prevent thrombohemorrhagic complications

•Red cells may be eliminated by apheresis or phlebotomy

•Cytotoxic agents can be associated with an increased risk of developing leuke- mia; hydroxyurea may be used if there are more than 1,000×109 platelets/l

5.4Essential Thrombocythemia

Secondary (reactive) thrombocytosis (more than 450 × 109/l): acute and chronic infectious diseases, hemolytic anemia, iron deficiency, trauma, surgery, renal disorders, blood loss, postsplenectomy, drugs (e.g., corticosteroids)

5.4.1Differential Diagnosis

•Differential diagnosis: reactive thrombocytosis, myeloproliferative disorders

•Essential thrombocythemia (ET) with autosomal dominant inheritance

5.4.2Diagnosis

•Platelets: more than 600 × 109/l

•Hemoglobin: up to 130 g/l

•Normal iron levels

•No Philadelphia chromosome, t(9;22)

•No bone marrow fibrosis

•No signs of secondary thrombocytosis

•Somatic JAK2 V617F mutation may be present; rarely, mutations in the gene coding for thrombopoietin receptor have been found

•The overlapping clinical and biologic features of polycythemia vera, essential thrombocythemia, and primary myelofibrosis may be reflected by a common JAK2 which may occur in all mentioned disorders

•JAK2 mutations seem not to be an initiating, but rather a late event in the molecular evolution of myeloproliferative neoplasms. This may have implications for