(Idiopathic Thrombocytopenic Purpura)
Immune thrombocytopenic purpura (ITP) is a bleeding disorder caused by thrombocytopenia not associated with a systemic disease. Typically, it is chronic in adults but is usually acute and self-limited in children. Spleen size is normal. Diagnosis requires that other disorders be excluded through selective tests. Treatment includes corticosteroids, splenectomy, and immunosuppressants and thrombopoietic-mimetic drugs. For life-threatening bleeding, platelet transfusions, IV corticosteroids, and IV immune globulin are required.
ITP usually results from development of an autoantibody directed against a structural platelet antigen. In childhood ITP, the autoantibody may be triggered by binding of viral antigen to megakaryocytes.
Symptoms and Signs
The symptoms and signs are petechiae, purpura, and mucosal bleeding. Gross GI bleeding and hematuria are uncommon. The spleen is of normal size unless it is enlarged by a coexisting childhood viral infection.
ITP is suspected in patients with isolated thrombocytopenia (ie, otherwise normal CBC and peripheral blood smear). Because manifestations of ITP are nonspecific, other causes of isolated thrombocytopenia (eg, drugs, alcohol, lymphoproliferative disorders, systemic illness) need to be excluded by clinical evaluation and appropriate testing. Typically, patients have coagulation studies, liver function tests (including testing for hepatitis C), and, because HIV-associated thrombocytopenia may be otherwise indistinguishable from ITP, HIV testing. Testing for antiplatelet antibodies does not aid diagnosis or treatment.
Bone marrow examination is not required to make the diagnosis but is done if blood counts or blood smear reveals abnormalities in addition to thrombocytopenia, when clinical features are not typical, and in patients > 60 yr (because myelodysplasia is more common in older patients). In patients with ITP, bone marrow examination reveals normal or possibly increased numbers of megakaryocytes in an otherwise normal bone marrow sample.
Children typically recover spontaneously, even from severe thrombocytopenia, in several weeks to months.
In adults, spontaneous remission is rare. However, some have mild and stable disease (ie, platelet counts > 30,000/μL); such cases may be more common than previously thought, many being discovered by the automated platelet counting now routinely done with CBC. Others have significant, symptomatic thrombocytopenia, although life-threatening bleeding and death are rare.
Adults usually are given an oral corticosteroid (eg, prednisone 1 mg/kg once/day) initially. In patients who respond, the platelet count rises to normal within 2 to 6 wk. The corticosteroid dosage is then tapered. An alternative corticosteroid regimen is dexamethasone 40 mg po once/day for 4 days. However, most patients do not respond adequately or relapse as the corticosteroid is tapered. Splenectomy can achieve a complete remission in about two thirds of these patients but is usually reserved for those with severe thrombocytopenia, bleeding, or both; it may not be appropriate for those with mild disease. Rituximab (375 mg/m2 IV once/wk for 4 wk) may be used in patients who do not respond to splenectomy or in patients who are not candidates for splenectomy.
Because other treatments may not be effective for patients with ITP refractory to corticosteroids and splenectomy and because ITP often has a benign natural history, additional treatments may not be indicated unless the platelet count is < 10,000 to 20,000/μL and active bleeding is present. In these patients, thrombopoietin-mimetic drugs, such as romiplostim 1 to 5 μg/kg sc once/wk and eltrombopag 50 to 75 mg po once/day, may be used.
About 75 to 80% of patients respond to thrombopoietin-mimetic drugs even after failure of multiple previous treatments. However, these drugs are used for maintenance therapy rather than induction of remission and need to be administered continuously to maintain the platelet count > 50,000/μL. More intensive immunosuppression may be required with drugs such as cyclophosphamide and azathioprine in patients unresponsive to other drugs who have severe, symptomatic thrombocytopenia.
Treatment of children is usually supportive, because most children spontaneously recover. Even after months or years of thrombocytopenia, most children have spontaneous remissions. If mucosal bleeding occurs, corticosteroids or IV immune globulin is given. Initial use of corticosteroids and IV immune globulin is controversial, because they increase platelet count but may not improve clinical outcome. Splenectomy is rarely done in children. However, if thrombocytopenia is severe and symptomatic for > 6 mo, then splenectomy is effective.
In children or adults with ITP and life-threatening bleeding, rapid phagocytic blockade is attempted by giving IV immune globulin 1 g/kg once/day for 1 to 2 days. This treatment usually causes the platelet count to rise within 2 to 4 days, but the count remains high only for 2 to 4 wk. High-dose methylprednisolone (1 g IV once/day for 3 days) is less expensive than IV immune globulin and is easier to administer but may not be as effective. Patients with ITP and life-threatening bleeding are also given platelet transfusions. Platelet transfusions are not used prophylactically.
Oral corticosteroids or IV immune globulin may also be given when a transient increase of the platelet count is required for tooth extractions, childbirth, surgery, or other invasive procedures.
Last full review/revision May 2009 by James N. George, MD