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Idiopathic Thrombocytopenic Purpura

The most common cause of acute onset of thrombocytopenia in an otherwise well child is (autoimmune) idiopathic thrombocytopenic purpura (ITP).

In a small number of children, 1–4 wk after exposure to a common viral infection, an autoantibody directed against the platelet surface develops. The exact antigenic target for most such antibodies in most cases of acute ITP remains undetermined. After binding of the antibody to the platelet surface, circulating antibody-coated platelets are recognized by the Fc receptor on the splenic macrophages, ingested, and destroyed. A recent history of viral illness is described in 50–65% of cases of childhood ITP. The reason why some children respond to a common infection with an autoimmune disease remains unknown. Most common infectious viruses have been described in association with ITP, including Epstein-Barr virus and HIV. Epstein-Barr virus–related ITP is usually of short duration and follows the course of infectious mononucleosis. HIV-associated ITP is usually chronic.

The classic presentation of ITP is that of a previously healthy 1–4 yr old child who has sudden onset of generalized petechiae and purpura. The parents often state that the child was fine yesterday and now is covered with bruises and purple dots. Often there is bleeding from the gums and mucous membranes, particularly with profound thrombocytopenia (platelet count <10 × 109/L). There is a history of a preceding viral infection 1–4 wk before the onset of thrombocytopenia. Findings on physical examination are normal, other than the finding of petechiae and purpura. Splenomegaly is rare, as is lymphadenopathy or pallor. An easy to use classification system has been proposed from the U.K. to characterize the severity of bleeding in ITP on the basis of symptoms and signs, but not platelet count: 1. 2. 3. 4. No symptoms Mild symptoms: bruising and petechiae, occasional minor epistaxis, very little interference with daily living Moderate: more severe skin and mucosal lesions, more troublesome epistaxis and menorrhagia Severe: bleeding episodes—menorrhagia, epistaxis, melena—requiring transfusion or hospitalization, symptoms interfering seriously with the quality of life

The presence of abnormal findings, such as hepatosplenomegaly or remarkable lymphadenopathy, suggests other diagnoses (leukemia). When the onset is insidious, especially in an adolescent, chronic ITP or the possibility that thrombocytopenia is a

Disorders that cause increased platelet destruction on a nonimmune basis are usually serious systemic illnesses with obvious clinical findings (e. Bone marrow examination shows normal granulocytic and erythrocytic series. white blood cell (WBC) count. Some of the megakaryocytes may appear to be immature and are reflective of increased platelet turnover. In 70–80% of children who present with acute ITP. hemolytic-uremic syndrome [HUS]. LABORATORY FINDINGS. disseminated intravascular coagulation [DIC]). especially sexually active teens. In adolescents with new-onset ITP. and differential count should be normal. an antinuclear antibody test should be done to evaluate for SLE. Therapy does not appear to affect the natural history of the illness. Other than congenital syndromes. and rarely. Isolated enlargement of the spleen suggests the potential for hypersplenism owing to either liver disease or portal vein thrombosis. Those who favor interventional therapy argue that the objective of early therapy is to raise the platelet count to >20 × 109/L and prevent the rare development of intracranial hemorrhage. A Coombs test should be done if there is unexplained anemia to rule out Evans syndrome (autoimmune hemolytic anemia and thrombocytopenia) [see Chapter 464 ] or before instituting therapy with IV anti-D. Platelet antibody testing is seldom useful in acute ITP. Hemoglobin may be decreased if there have been profuse nosebleeds or menorrhagia. Wiskott-Aldrich syndrome must be considered in young males found . Indications for bone marrow aspiration include an abnormal WBC count or differential or unexplained anemia as well as findings suggestive of bone marrow disease on history and physical examination. or rarely. HIV studies should be done in at-risk populations. spontaneous resolution occurs within 6 mo. and platelet size is normal or increased.manifestation of a systemic illness. DIFFERENTIAL DIAGNOSIS. Fewer than 1% of patients have intracranial hemorrhage. Autoimmune thrombocytopenia may be an initial manifestation of SLE. such as systemic lupus erythematosus (SLE). The well-appearing child with moderate to severe thrombocytopenia. HIV infection. In acute ITP. such as amegakaryocytic thrombocytopenia and thrombocytopenia-absent radius (TAR) syndrome. most marrow processes that interfere with platelet production also cause abnormal synthesis of red blood cells (RBCs) and WBCs and therefore manifest diverse abnormalities on the CBC. and normal findings on physical examination has a limited differential diagnosis that includes exposure to medication that induces drug-dependent antibodies. splenic sequestration due to previously unappreciated portal hypertension. is more likely. Severe thrombocytopenia (platelet count <20 × 109/L) is common. Approximately 20% of children who present with acute ITP go on to have chronic ITP. reflective of increased platelet turnover. early aplastic processes. with characteristically normal or increased numbers of megakaryocytes. such as Fanconi anemia. an otherwise normal complete blood cell count (CBC).g. lymphoma. Other laboratory tests should be done as indicated by the history and physical examination. the hemoglobin value..

Doses of prednisone of 1–4 mg/kg/24 hr appear to induce a more rapid rise in platelet count than in untreated patients with ITP. There are no data showing that treatment affects either short. TREATMENT. with a rapid taper to avoid the long-term side effects of corticosteroid therapy. mild. IVIG appears to induce a response by downregulating Fc-mediated phagocytosis of antibody-coated platelets. and moderate have low platelet counts. Intravenous immunoglobulin (IVIG). No therapy other than education and counseling of the family and patient for patients with minimal. diabetes mellitus. which commonly occur several wk after an initial course of therapy. particularly if there is a history of eczema and recurrent infection.8–1. Many patients with new-onset ITP have mild symptoms. Corticosteroid therapy has been used for many years to treat acute and chronic ITP in adults and children. although there are no data indicating that early therapy prevents intracranial hemorrhage. especially growth failure. . Whether bone marrow examination should be performed to rule out other causes of thrombocytopenia. 3. Initial approaches to the management of ITP include the following: 1. platelet transfusion in ITP is usually contraindicated unless life-threatening bleeding is present. This approach emphasizes the usually benign nature of ITP and avoids the therapeutic roller coaster that ensues once interventional therapy is begun. there is a high frequency of headaches and vomiting. 4. Each of these medications may be used to treat exacerbations of ITP. Antiplatelet antibodies bind to transfused platelets as well as they do to autologous platelets. and side effects are minimal. Intravenous anti-D therapy. before institution of prednisone therapy in acute ITP is controversial. Prednisone. especially acute lymphoblastic leukemia. This approach is far less costly. IV antiD is ineffective in Rh negative patients. after infusion. Additionally. Compared with untreated control subjects. as defined earlier. IVIG therapy is both expensive and time-consuming to administer. IV anti-D induces mild hemolytic anemia.0 g/kg/day for 1–2 days induces a rapid rise in platelet count (usually>20× 109/L) in 95% of patients within 48 hr. RBC-antibody complexes bind to macrophage Fc receptors and interfere with platelet destruction. and osteoporosis. When given to Rh positive individuals. For Rh positive patients. suggestive of IVIG-induced aseptic meningitis. thereby causing a rise in platelet count. with findings limited to petechiae and purpura on the skin. despite severe thrombocytopenia. IV anti-D at a dose of 50– 75μg/kg causes a rise in platelet count to>20× 109/L in 80–90% of patients within 48–72 hr. treatment appears to be capable of inducing a more rapid rise in platelet count to the theoretically safe level of >20 × 109/L. 2. Corticosteroid therapy is usually continued for 2–3 wk or until a rise in platelet count to>20× 109/L has been achieved.or long-term clinical outcome of ITP. Thus. IVIG at a dose of 0.

a thrombopoiesis-stimulating protein. Intracranial hemorrhage remains rare. but there is significant disagreement within the field. such as SLE. such as HIV. and there are no data showing that treatment actually reduces its incidence. or rituximab (see Chapter 464 ). Approximately 20% of patients who present with acute ITP have persistent thrombocytopenia for > 6 mo and are said to have chronic ITP. chronic infectious disorders. and nonimmune causes of chronic thrombocytopenia. CHRONIC IDIOPATHIC THROMBOCYTOPENIC PURPURA. 484. Splenectomy is successful in inducing complete remission in 64– 88% of children with chronic ITP. a careful reevaluation for associated disorders should be performed. such as IVIG. especially for autoimmune disease. AMG 531. autosomal macrothrombocytopenia. with plans for emergency splenectomy. corticosteroids. Whether penicillin prophylaxis should be lifelong is controversial. The role of splenectomy in ITP should be reserved for 1 of 2 circumstances. such as type 2B and platelet-type von Willebrand disease. The American Society of Hematology has published treatment guidelines for adults with ITP. X-linked thrombocytopenia. and prompt surgical consultation. and these may represent only 5% of children with ITP. and WAS (also X-linked). This decision is often affected by lifestyle issues as well as the ease with which the child can be managed using medical therapy. The only consensus is that patients who are bleeding significantly should be treated. Therapy should be aimed at controlling symptoms and preventing serious bleeding. the child should receive pneumococcal and meningococcal vaccines. Before splenectomy. IV anti-D. high-dose corticosteroids. and after splenectomy. autoimmune lymphoproliferative syndrome. The older child (> 4 yr) with severe ITP that has lasted >1 yr (chronic ITP) and whose symptoms are not easily controlled with therapy is a candidate for splenectomy. In ITP. including platelet transfusion. IVIG. Currently.In the special case of intracranial hemorrhage. At that time. Splenectomy must also be considered when life-threatening hemorrhage (intracranial hemorrhage) complicates acute ITP. common variable immunodeficiency syndrome. he or she should receive penicillin prophylaxis for a number of yr. has had some success in treating adults with chronic immune thrombocytopenia. multiple modalities should be used.2 Drug-Induced Thrombocytopenia . if the platelet count cannot be corrected rapidly with transfusion of platelets and administration of IVIG and corticosteroids. Splenectomy is associated with a lifelong risk of overwhelming postsplenectomy infection caused by encapsulated organisms. the spleen is the primary site of both antiplatelet antibody synthesis and platelet destruction. This must be balanced against the lifelong risk of overwhelming postsplenectomy infection. there is no consensus regarding the management of acute childhood ITP.

sulfonamides. and trimethoprim-sulfamethoxazole. Heparin-induced thrombocytopenia (and rarely.A number of drugs are associated with immune thrombocytopenia as the result of either an immune process or megakaryocyte injury. the patient has an antibody directed against the heparin-platelet factor 4 complex. but it occurs when. . Some common drugs used in pediatrics that cause thrombocytopenia include valproic acid. phenytoin. after exposure to heparin. thrombosis) is seldom seen in pediatrics.