Primary thrombocythemia (also called essential thrombocythemia) is a stem cell disorder within the bone marrow. A marked increase in platelet production occurs, with the platelet count consistently greater than 600,000/mm3. Platelet size may be abnormal, but platelet survival is typically normal. Occasionally, the platelet in-crease is accompanied by an increase in RBCs or WBCs or both; however, these cells are not increased to the extent that they are in polycythemia vera, CML, or myelofibrosis. Although the exact cause is unknown, primary thrombocythemia is similar to other myeloproliferative disorders, particularly polycythemia vera. Un-like the other myeloproliferative disorders, however, it rarely evolves into acute leukemia.
Many patients with primary thrombocythemia are asymptomatic; the illness is diagnosed as the result of finding an elevated platelet count on a CBC. Symptoms, when they do occur, result primarily from hemorrhage or vasoocclusion in the microvasculature. Symp-toms may occur more when the platelet count exceeds 1 million/ mm3. However, symptoms do not always correlate with the extent to which the platelet count is elevated. Thrombosis is common and can be either arterial or venous; major thromboses occur in 15% to 40% of these patients (Jantunen et al., 2001). Because these platelets can be dysfunctional, minor or major hemorrhage can also occur. Bleeding from the mucous membranes of the nose and mouth is common, and significant gastrointestinal bleeding is also possible. Bleeding typically does not occur until the platelet count exceeds 1 million/mm3.
Vasoocclusive manifestations are most frequently seen in the form of erythromelalgia. The toxic effects of platelet substances include painful burning, warmth, and redness in a localized dis-tal area of the extremities. Neurologic manifestations may also be seen, such as numbness, tingling, and visual disturbance; these occlusive manifestations can progress to stroke and seizure and, less commonly, to myocardial infarction. The spleen may be en-larged, but usually not to a significant extent.
The diagnosis of primary thrombocythemia is made by ruling out other potential disorders. Iron deficiency should be excluded, be-cause a reactive increase in the platelet count often accompanies this deficiency. The myeloproliferative disorders (CML, poly-cythemia vera) should also be excluded. Examination of the CBC shows markedly abnormal platelets. Analysis of the bone marrow (by aspiration and biopsy) shows a marked increase in megakaryo-cytes (platelet precursors) and is useful in excluding CML as a possible cause for the elevated platelet count. The disease, which affects men and women equally, tends to occur in late middle age. The median survival time exceeds 10 years.
No data reliably predict the development of complications. Risk factors for the development of thrombotic complications are age greater than 65 years, prior thrombotic events, and long du-ration of thrombocytosis. Major bleeding tends to occur when the platelet count is very high.
The management of primary thrombocythemia is highly contro-versial. The risk of significant thrombotic or hemorrhagic com-plications may not be increased until the platelet count exceeds 1 million/mm3 (Briere & Guilmin, 2001). A careful assessment of other risk factors, such as history of peripheral vascular disease, history of tobacco use, atherosclerosis, and prior thrombotic events, should be used in making the decision as to when to ini-tiate therapy. In younger patients with no risk factors, low-dose aspirin therapy may be sufficient to prevent thrombotic compli-cations; however, the use of aspirin can increase the risk for hemorrhagic complications and may be considered a contraindi-cation in patients with a history of gastrointestinal bleeding. The neurologic symptoms (eg, headache and erythromelalgia) and vi-sual symptoms of primary thrombocytopenia can be relieved by low-dose aspirin.
More aggressive measures may be required in older patients and in those with concurrent risk factors. Hydroxyurea (eg, Hydrea), a chemotherapeutic medication, is effective in lowering the platelet count. It is taken orally and causes minimal side effects other than dose-related leukopenia. However, its potential for leukogenesis is in question. The medication anagrelide (Agrylin) is more specific in lowering the platelet count than is hydroxyurea, but it has more side effects. Severe headaches cause many patients to stop taking the medication. Tachycardia and chest pain may also occur, and anagrelide is contraindicated in patients with concurrent cardiac problems. Interferon-alfa-2b (eg, Intron-A) has been shown to lower platelet counts by an unknown mechanism. The medication is administered subcutaneously at varying frequency, commonly three times per week. Significant side effects, such as fatigue, weak-ness, memory defects, dizziness, anemia, and liver dysfunction, limit its usefulness.
Rarely, the occlusive symptoms are so great that the platelet count must be reduced immediately. Platelet pheresis (see later discussion) can reduce the amount of circulating platelets, but only transiently. The extent by which symptoms and complica-tions (eg, thromboses) are reduced remains unclear.
Patients with primary thrombocythemia need to be instructed about the accompanying risks of hemorrhage and thrombosis. Patients should be informed about signs and symptoms of thrombosis, particularly the neurologic manifestations, such as vi-sual changes, numbness, tingling, and weakness. Risk factors for thrombosis should be assessed, and measures to diminish risk fac-tors (particularly cessation of tobacco use) should be encouraged. Patients receiving aspirin therapy should be informed about the increased risk for bleeding. Patients who are at risk for bleeding should be instructed about medications that can alter platelet function, such as aspirin, NSAIDs, and alcohol. Patients receiv-ing interferon therapy should be taught to self-administer the medication and manage side effects.
Increased platelet production is the primary mechanism of sec-ondary, or reactive, thrombocytosis. The platelet count is above normal, but, in contrast to primary thrombocythemia, an increase above 1 million/mm3 is rare. Platelet function is normal; the plate-let survival time is normal or decreased. Symptoms associated with hemorrhage or thrombosis are rare. Many disorders can cause a reactive increase in platelets, including chronic inflammatory dis-orders, iron deficiency, malignant disease, acute hemorrhage, and splenectomy (see previous discussion of primary thrombocythe-mia). Treatment is aimed at the underlying disorder. With suc-cessful management, the platelet count usually returns to normal.