Immune Thrombocytopenia (ITP)
(Idiopathic Thrombocytopenic Purpura; Immune Thrombocytopenic Purpura)
Immune thrombocytopenia (ITP) is a bleeding disorder caused by thrombocytopenia not associated with a systemic disease. Typically, it is chronic in adults, but it is usually acute and self-limited in children. Spleen size is normal in the absence of another underlying condition. Diagnosis requires that other disorders be excluded through selective tests. Treatment includes corticosteroids, splenectomy, immunosuppressants, and thrombopoietin receptor agonist drugs. For life-threatening bleeding, platelet transfusions, IV corticosteroids, IV anti-D immune globulin, or IV immune globulin may be used individually or in combination.
(See also Overview of Platelet Disorders.)
Immune thrombocytopenia 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, although in some countries (eg, Japan, Italy), ITP has been associated with Helicobacter pylori infection, and treatment of the infection has been followed by remission of the ITP. ITP tends to worsen during pregnancy and increases the risk of maternal morbidity (see Immune Thrombocytopenia (ITP) in Pregnancy).
The symptoms and signs of immune thrombocytopenia are
Gross GI bleeding and hematuria are less common. The spleen is of normal size unless it is enlarged by a coexisting viral infection or autoimmune hemolytic anemia (Evans syndrome). Like the other disorders of increased platelet destruction, ITP is also associated with an increased risk of thrombosis.
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 usually 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.
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.
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. The majority of patients respond with a rise in platelet count within 2 to 5 days, but in some patients, it may take as long as 2 to 4 wk before a response occurs; however, when the corticosteroid is tapered after response, most adult 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 an attempt to avoid splenectomy.
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.
Splenectomy can achieve a complete remission in about two thirds of patients who relapse after initial corticosteroid therapy, but it is usually reserved for patients with severe thrombocytopenia, bleeding, or both. Splenectomy 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 (1). Splenectomy results in an increased risk of thrombosis and infection (particularly with encapsulated bacteria such as pneumococcus); patients require vaccination against Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis (ideally > 2 wk before the procedure).
Second-line medical therapies are available for patients
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 receptor agonists, rituximab, and other immunosuppressive agents. Thrombopoietin receptor 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 receptor 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 (2).
More intensive immunosuppression may be required with drugs such as cyclophosphamide and azathioprine in patients unresponsive to other drugs who have severe, symptomatic thrombocytopenia.
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, in Rh positive patients, a single dose of IV anti-D immune globulin 75 mcg/kg. IV anti-D immunoglobulin is only effective in patients who have not had a splenectomy and may be associated with severe complications such as severe hemolysis and disseminated intravascular coagulation. 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. Vincristine (1.4 mg/kg; maximum dose of 2 mg) has also been used in emergency situations.
Treatment of children with ITP 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 thrombopoietin receptor agonists (romiplostim, eltrombopag) or splenectomy is considered.
1. Neunert C, Lim W, Crowther M, et al: The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood 117:4190–4207, 2011.
2. Patel VL, Mahevas M, Lee SY, et al: Outcomes 5 years after response to rituximab therapy in children and adults with immune thrombocytopenia. Blood 119:5989–5995, 2012.
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.