ESSENTIALS OF DIAGNOSIS
Elevated platelet count in absence of other causes.
Normal red blood cell mass.
Absence of bcr/abl gene (Philadelphia chromosome).
Essential thrombocytosis is an uncommon myeloproliferative disorder of unknown cause in which marked proliferation of the megakaryocytes in the bone marrow leads to elevation of the platelet count. As with polycythemia vera, the finding of a high frequency of mutations of JAK2 and others in these patients has advanced the understanding of this disorder.
The median age at presentation is 50–60 years, and there is a slightly increased incidence in women. The disorder is often suspected when an elevated platelet count is found. Less frequently, the first sign is thrombosis, which is the most common clinical problem. The risk of thrombosis rises with age. Venous thromboses may occur in unusual sites such as the mesenteric, hepatic, or portal vein. Some patients experience erythromelalgia, painful burning of the hands accompanied by erythema; this symptom is reliably relieved by aspirin. Bleeding, typically mucosal, is less common and is related to a concomitant qualitative platelet defect. Splenomegaly is present in at least 25% of patients.
An elevated platelet count is the hallmark of this disorder, and may be over 2,000,000/mcL (2000 × 109/L) (Table 13–14). The white blood cell count is often mildly elevated, usually not above 30,000/mcL (30 × 109/L), but with some immature myeloid forms. The hematocrit is normal. The peripheral blood smear reveals large platelets, but giant degranulated forms seen in myelofibrosis are not observed. Red blood cell morphology is normal.
The bone marrow shows increased numbers of megakaryocytes but no other morphologic abnormalities. The peripheral blood should be tested for the bcr/abl fusion gene (Philadelphia chromosome) since it can differentiate CML, where it is present, from essential thrombocytosis, where it is absent.
Essential thrombocytosis must be distinguished from secondary causes of an elevated platelet count. In reactive thrombocytosis, the platelet count seldom exceeds 1,000,000/mcL (1000 × 109/L). Inflammatory disorders such as rheumatoid arthritis and ulcerative colitis cause significant elevations of the platelet count, as may chronic infection. The thrombocytosis of iron deficiency is observed only when anemia is significant. The platelet count is temporarily elevated after a splenectomy. JAK2 mutations are found in over 50% of cases. MPL and CALR mutations frequently occur in patients with JAK2-negative essential thrombocytosis.
Regarding other myeloproliferative disorders, the lack of erythrocytosis distinguishes it from polycythemia vera. Unlike myelofibrosis, red blood cell morphology is normal, nucleated red blood cells are absent, and giant degranulated platelets are not seen. In CML, the Philadelphia chromosome (or bcr/abl by molecular testing) establishes the diagnosis.