(Idiopathic Thrombocytopenic Purpura; Immune Thrombocytopenic Purpura; ITP)

Immune thrombocytopenia (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, immunosuppressants, and thrombopoietin agonist drugs. For life-threatening bleeding, platelet transfusions, IV corticosteroids, IV anti-D immune globulin, and IV immunoglobulin 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 viral antigens. The trigger in adults is unknown.

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. Like the other disorders of increased platelet destruction, ITP is also associated with an increased risk of thrombosis.

Diagnosis

• CBC with platelets, peripheral blood smear
• Sometimes bone marrow aspiration
• Exclusion of other thrombocytopenic disorders

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, other autoimmune diseases, viral infections) need to be excluded by clinical evaluation and appropriate testing. Typically, patients have coagulation studies, liver function tests, and tests for infection with hepatitis C and HIV. 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, or if patients fail to respond to standard therapies. In patients with ITP, bone marrow examination reveals normal or possibly increased numbers of megakaryocytes in an otherwise normal bone marrow sample.

Prognosis

Children typically recover spontaneously, even from severe thrombocytopenia, in several weeks to months.

In adults, spontaneous remission may occur, but it is uncommon after the first year of disease. However, many patients have mild and stable disease (ie, platelet counts > 30,000/μL) with minimal or no bleeding; such cases may be more common than previously thought, many being discovered by the automated platelet counting now routinely done with CBC. Other patients have significant, symptomatic thrombocytopenia, although life-threatening bleeding and death are rare.

Treatment

• Oral corticosteroids
• IV immunoglobulin (IVIG)
• IV anti-D immune globulin
• Splenectomy
• Thrombopoietin agonist drugs
• Rituximab
• Other immunosuppressants
• For severe bleeding, IVIG, IV anti-D immune globulin, IV corticosteroids, and/or platelet transfusions

Adults with bleeding and a platelet count < 30,000/µL are usually given an oral corticosteroid (eg, prednisone 1 mg/kg po once/day) initially. An alternative, but probably less effective, corticosteroid regimen is dexamethasone 40 mg po once/day for 4 days. If there is concurrent severe bleeding or a need to rapidly increase the platelet count, IVIG or IV anti-D immune globulin may be added to the corticosteroids. Most patients respond with a rise in platelet count in 2 to 4 wk; however, when the corticosteroid is tapered, following response, most patients relapse. Repeated corticosteroid treatments may be effective, but increase the risk of adverse effects. Corticosteroids should not usually be continued beyond the first several months; other drugs may be tried in attempt to avoid splenectomy.

Splenectomy can achieve a complete remission in about two thirds of patients who relapse but is usually reserved for those with severe thrombocytopenia, bleeding, or both; it may not be appropriate for patients with mild disease. If thrombocytopenia can be controlled with medical therapies, splenectomy is often deferred for 6 to 12 mo to allow for the chance of spontaneous remission.

Second-line medical therapies are available for patients who are seeking to defer splenectomy in hope of a spontaneous remission, those who are not candidates for or refuse splenectomy, and those in whom splenectomy has not been effective. Such patients usually have platelet counts < 10,000 to 20,000/μL (and thus are at risk for bleeding). Second-line medical therapies include thrombopoietin agonists, rituximab, and other immunosuppressive agents. Thrombopoietin agonist drugs, such as romiplostim 1 to 10 mcg/kg sc once/wk and eltrombopag 25 to 75 mg po once/day have response rates > 85%. However, thrombopoietin agonists need to be administered continuously to maintain the platelet count > 50,000/μL. Rituximab (375 mg/m² IV once/wk for 4 wk) has a response rate of 57%, but only 21% of adult patients remain in remission after 5 yr. 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 IVIG may be given. Corticosteroid and IVIG use is controversial because the increased platelet count may not improve clinical outcome. Splenectomy is rarely done in children. However, if thrombocytopenia is severe and symptomatic for > 6 mo, then splenectomy is a consideration.

In children or adults with ITP and life-threatening bleeding, rapid phagocytic blockade is attempted by giving IVIG 1 g/kg once/day for 1 to 2 days or a single dose of IV anti-D immune globulin 75 mcg/kg. This treatment usually causes the platelet count to rise within 2 to 4 days, but the count remains high for only 2 to 4 wk. High-dose methylprednisolone (1 g IV once/day for 3 days) is less expensive than IVIG or IV anti-D 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 IVIG or IV anti-D 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.

Key Points

• The immune system destroys platelets in the circulation and at the same time attacks bone marrow megakaryocytes, thereby reducing platelet production.
• Other causes of isolated thrombocytopenia (eg, drugs, alcohol, lymphoproliferative disorders, other autoimmune diseases, viral infections) need to be excluded.
• Children usually have spontaneous remission; in adults, spontaneous remission may occur during the first year but is uncommon thereafter.
• Corticosteroids (and sometimes IVIG or IV anti-D immune globulin) are first-line treatments for bleeding or severe thrombocytopenia.
• Splenectomy is often effective but is reserved for patients in whom medical therapy is ineffective or those whose disease persists after 12 mo.
• Platelet transfusion is given only for life-threatening bleeding.

Last full review/revision October 2012 by David J. Kuter