patients will often have anemia and immature granulocytes including myeloblasts in the peripheral blood and/or bone marrow. Thus, cytogenetic studies are crucial in excluding this diagnosis.

In the absence of causes of secondary thrombocytosis, a diagnosis of ET may be considered when a patient is found with an increased platelet count (>400,000/^L), symptoms of thrombosis (usually), or hemorrhage. ET is a disease characterized by an increased platelet count owing to proliferation of an abnormal clone of megakaryocytes unresponsive to normal control mechanisms governing platelet production.

ET affects young and middle-aged women and men. Recurrent thromboses and, paradoxically, bleeding are the cardinal features. Although some patients, particularly younger ones, remain asymptomatic for long periods, approximately 50% of patients with ET are first seen as emergencies because of an episode of vascular occlusion that may be either arterial, venous, or both.

In our center, most younger patients present with thromboses rather than hemorrhage. Variable symptoms and signs include transient ischemic attacks, stroke, thrombosis of the splenic and/or hepatic veins, and evidence of peripheral circulatory impairment characterized by digital cyanosis, erythromelalgia, and pain and burning owing to microvascular clogging of small vessels by platelets. Clinical bleeding is manifested by easy bruising, bleeding of mucosal surfaces, epistaxis, unexplained hemorrhage, and postoperative hemorrhage.

Aside from the physical findings related to the aforementioned, physical examination of the asymptomatic patient is usually unremarkable. About one third of asymptomatic patients have splenomegaly, which is only modest in degree (1-3 cm below the left costal margin).

The peripheral smear shows clusters and clumps of megakaryocytes and giant platelets. Granulocyte and RBC morphology is essentially normal. The WBC is slightly increased in a minority of patients. Cytogenetic abnormalities (not related to the Ph chromosome diagnostic of CML) are present in only a few patients with ET. The overall significance of cytoge-netic abnormalities in terms of clinical course and prognosis is unclear.

Sometimes, an often unrecognized and curious laboratory abnormality may lead to the diagnosis of ET in asymptomatic patients. When a routine electrolyte panel is submitted for analysis, an artificially abnormal high potassium value may be found. This is due to loss of potassium released from large numbers of platelets, which occurs during clotting in vitro. This abnormality is not associated with any deleterious clinical effect. This spuriously high potassium value is known as pseudohyperkalemia. If a potassium determination is required from a patient with ET, a plasma sample, wherein unclotted blood is submitted for laboratory analysis, will avoid this problem.

As in PV, abnormalities of the MpL receptor abnormality1617 and the PRV-1 gene occur in ET.18 As yet, the practical clinical use of these two tests remains to be established. Abnormal JAK2 expression has been observed in approximately 50% of patients with ET. It has been suggested that the course of JAK2 (+) patient may be more aggresive than JAK2 (—) patients but it is too soon to rely in this statement as fact.19 Thus, ET is largely based on exclusion of secondary reactive causes of thrombocytosis.

Recently, in ET, the morphologic changes in marrow megakaryocytes have been appreciated.20 Thus, all patients with a presumptive diagnosis of ET should have a marrow biopsy performed. In reactive thrombocytosis, the number of megakaryocytes is slightly-to-moderately increased, but size and nuclear lobulation remain normal; there is no tendency for megakaryocytes to cluster together. Megakaryocytes in ET, increased in number, are scattered or loosely grouped within the bone marrow. ET megakaryocytes are characterized by large, giant-sized megakary-ocytes and exhibit deeply lobulated staghorn-like nuclei. Sheets and clumps of platelets may be associated with masses of platelet debris.

The platelet abnormality occurring in ET cannot be quantified by any measure of platelet dysfunction; despite a great deal of research, the pathophysiologic basis for excessive bleeding and thrombosis is not clearly understood. The results of in vitro platelet function tests are variable and show impaired or absent epi-nephrine-induced platelet aggregation. There is no exact correlation between the platelet count and thrombosis or hemorrhage, although in general, the higher the platelet count, the greater is the likelihood of these events occurring.

The diagnostic criteria for ET are shown in Table 47.6. These criteria are based on modified criteria proposed originally by the Polycythemia Vera Study Group (PVSG) and the World Health Organization.21 All criteria must be fulfilled to make a diagnosis of ET. Note that collagen fibrosis of the marrow in 1/3 of the marrow was allowed by the PVSG. Permitting this degree of fibrosis may confuse ET with early cases of AMM (MMM).

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