Essential Thrombocythemia: Diagnosis and Treatment, with Special Emphasis on the Use of Anagrelide

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Essential thrombocythemia (ET) is a myeloproliferative disorder of heterogeneous nature. It is characterized by megakaryocytic hyperplasia that leads to an elevated circulating platelet count [1–3]. A marked thrombocytosis can also be part of polycythemia vera (PV), chronic myeloid leukemia (CML) and agnogeneic myeloid metaplasia (AMM). In addition, thrombocytosis is often seen in conjunction with hemorrhage, infection, inflammatory states, malignant disease and after splenectomy. It was therefore even questioned for long time, if ET was a distinct entity or just a symptom of various other conditions. ET has, however, been convincingly demonstrated to be a clonal disorder, some patients have clonal involvement of at least one other cell lineage, whereas others demonstrate a polyclonal origin of all cell lineages outside of the megakaryocyte series [4–6]. This probably indicates, that genetic alterations at various levels of maturation of the pluripotent stem cell can lead to a similar clinical syndrome. The clinical diagnosis of ET is mostly based on exclusion of other, better defined, entities such as the above mentioned PV, CML and AMM. The establishment of the PV study group has made major contributions in (1) the development of criteria for the diagnosis of different myeloproliferative disorders (MPD), (2) collection of information around the epidemiology, natural history and pathophysiology and (3) systematic prospective clinical trials to determine optimal treatment programs for patients with MPD, primarily PV. The development of diagnostic criteria for PV and ET in 1975, and revised in 1986, has benefited the clinician in providing more stringent criteria for diagnosis of ET, since ET is a clinical diagnosis made partly by exclusion of other conditions [7]. Thus, for a diagnosis of ET the platelet count should be above 600,000 per microlitre without cause of reactive thrombocytosis such as, e.g. hemorrhage, infection, inflammatory disorder or malignancy. There should also be a normal red cell mass, i.e. ,36 ml per kg in males and ,32 ml per kg in females. Further, a determination of red cell mass and plasma volume is recommended to assist in distinguishing ET from PV if the hematocrit is ,60% in males and ,55% in females. Collagen fibrosis is usually absent on the bone marrow biopsy. The marrow is characterized by megakaryocytic hyperplasia, hypercellularity and usually presence of stainable iron [7,8]. There should be no cytogenetic abnormalities as associated with MDS, and the Philadelphia chromosome and/or bcr/abl abnormality associated with CML should not be present, the latter would be diagnostic of a CML variant rather than ET. Finally, in female patients the diagnosis is supported by clonal hematopoiesis when assaying gene markers for restriction fragment length polymorphisms on the X-chromosome [6]. The majority of patients with ET are discovered by chance when they have a routine blood count for unrelated reasons, but at least 20% of patients are diagnosed secondary to a clinical thromboembolic or hemorrhagic event, which may indicate an urgent need for medical intervention. At least another 30% of ET patients develop thrombotic problems during the course of their disease [8]. Microvascular complications are common, including erythromelalgia, acroparesthesies and neurological deficits, ranging