Essential Thrombocythemia

Chronic myeloproliferative disorder caused by a clonal increase in platelets resulting in thromboembolic and hemorrhagic complications.

Primary Thrombocytosis; Idiopathic Thrombocytosis; Hemorrhagic Thrombocytosis.

Estimated at 1.4-2.5:100,000 per year. Overall, both genders are approximately equally affected; however, there is a predilection for females at younger ages. Although the majority of patients at presentation are approximately 60 years old, approximately 20% of the patients are younger than 40 years. Only rarely has essential thrombocytosis (ET) been described in children.

Rare familial form with autosomal dominant transmission has been described. However, in the vast majority of patients, no genetic background is detectable.

Not fully elucidated yet. ET is caused by proliferation of megakaryocytes, of which the exact pathogenesis remains to be elucidated. However, evidence now indicates that a mutation of the thrombopoietin gene (located on 3q26.3-q27) may play a major role. Thrombopoietin is the key hormone in the regulation of megakaryocyte differentiation and proliferation. The mechanisms by which ET leads to thromboembolic and hemorrhagic complications remain unclear, although different laboratory findings have been used to explain them (intrinsic abnormality of the platelets resulting in hypoaggregation and hyperaggregation of platelets, anomalies or decreased concentrations of “von Willebrand factor,” or deficiencies of proteins C and S and/or antithrombin III).

Based on the clinical findings of a sustained, not otherwise explained platelet count greater than 600 × 109/liter, a hematocrit less than 40 (mild erythrocytosis is present in approximately one third of patients, while others have a mild hypochromic, microcytic anemia), and normal or increased leukocyte count. The mean platelet volume usually is increased, but microcytosis has also been described. Giant platelets can be found in the peripheral blood smear. A bone marrow aspirate and biopsy are needed and show an increased cellularity with megalokaryocytic predominance (often in clumps or sheets). Increased red and white cell hyperplasia are common. The stainable iron in the bone marrow, serum ferritin levels, and mean corpuscular erythrocyte volume are normal. Bone marrow fibrosis is either absent or affects less than one third of the biopsy area. No cytogenetic or morphologic evidence of a myelodysplastic syndrome can be found. No cause for reactive thrombocytosis. Essential thrombocythemia is diagnosed once reactive thrombocytosis has been excluded.

Up to 50% of patients present with microvascular occlusions (e.g., fingers and toes with risk of gangrene if left untreated, priapism), whereas major vessel occlusions (e.g., coronary, renal and femoral arteries, or hepatic-vein thrombosis [Budd-Chiari Syndrome], portal vein, splenic, or femoral vein thrombosis) are less common. Cerebrovascular infarction, transient ischemic attacks, and myocardial infarction, although common in elderly patients, are less common in young patients. Pulmonary embolism is a common finding and may result in chronic pulmonary artery hypertension. Hemorrhage can be a presenting feature, is generally not severe, and often is associated with platelet counts greater than 1000 × 109/liter, with the gastrointestinal tract (duodenum) the most common site of bleeding. Other sites of bleeding may include the urogenital tract, skin, gums, eyes, and central nervous system. Results of screening tests of coagulation usually are normal, but bleeding time may be prolonged. Splenomegaly and hepatomegaly (less common) are present in a significant number of patients. B symptoms (weight loss, fever, sweating) but also pruritus have been described in up to one third of patients. The risk of transformation into an acute leukemia reported in the literature varies between 2% and 20%. Death is usually the result of thromboembolic complications. Ten-year survival may be as high as 80%. Aspirin is the mainstay of management against recurrent thrombotic events (and places these patients at high risk for bleeding). Hydroxyurea, busulphan, and pipobroman have been used to lower very high platelet counts, although they may increase the rate of conversion to acute leukemia (leukemogenicity). This has suggested use of a conservative approach to management in younger patients. Anagrelide (an imidazoquinazoline compound that not only inhibits platelet aggregation but also results in suppression of megakaryocyte maturation with a decreased platelet count) has been used successfully to reduce the platelet count, while α-interferon currently is being investigated for use in ET. Plateletpheresis is used for patients with acute cerebrovascular complications or digital ischemia, for which rapid reduction of the platelet count is required.

A full examination for past or recent vascular occlusions, especially affecting the central nervous and/or cardiovascular systems but also kidneys and liver, is mandatory. A 12-lead electrocardiogram can help diagnose recent or old infarctions, major pulmonary embolism, or pulmonary hypertension. Echocardiography may be required to assess myocardial function and detect myocardial wall-motion abnormalities, myocardial scars from infarction and/or cor pulmonale, and signs of pulmonary hypertension. Laboratory investigations should include a complete blood count, coagulation studies (including bleeding time), serum concentrations of electrolytes (pseudohyperkalemia resulting from thrombocytosis), phosphate, urea, creatinine, and urate, and renal function. Pseudohypoxemia has been described in some patients, which is explained by the increased oxygen consumption in stored blood samples (so transport on ice and rapid processing of blood samples is recommended). Ensure appropriate fluid resuscitation and consider prophylaxis against thromboembolism. In approximately one third of patients, anagrelide may cause vasodilatory and positive inotropic effects, fluid retention, palpitations, arrhythmias, heart failure, and headache. Another side effect of this treatment may be a progressive anemia.

Ensure normovolemia throughout the perioperative period to minimize the risk of vascular occlusions and thromboembolic events. Avoid or limit the use of tourniquets when possible. Regional anesthesia has been used successfully; however, careful timing with thromboembolism prophylaxis and assessment of bleeding time is mandatory preoperatively, particularly for central neuraxial blockade.

No known specific implications for this condition.

Erythromelalgia: Disorder characterized by vasodilatation associated with paroxysmal, intense burning pain and episodic reddening of the extremities (mainly feet). The symptoms of redness, heat, pain, and swelling, when not associated with an organic disease, constitute the primary form, which has also been termed “erythermalgia” because of the significance of the heat. The secondary or acquired form is related to underlying medical conditions.