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Acute (Childhood) Immune Thrombocytopenia
Immune thrombocytopenia (ITP) is a bleeding disorder characterized by immune-mediated platelet destruction and resultant thrombocytopenia. Two forms of ITP had been described previously: acute ITP that resolves within 6 months and chronic ITP that persists beyond 6 months. Recently, an international working group on ITP has modified these designations to reflect the relatively common occurrence of spontaneous remission in children between 6 months and 1 year of diagnosis. Newly diagnosed ITP now denotes those within the first 3 months of diagnosis, persistent ITP refers to those between 3 months and 1 year of diagnosis, and chronic ITP now represents more than 1 year of disease persistence. ITP is one of the most common acquired bleeding disorders in the pediatric population, with an estimated prevalence of 4–8 per 100,000 children per year. Children typically present with severe thrombocytopenia but rarely have serious bleeding. In the majority of children, the disease resolves spontaneously over a period of weeks, irrespective of treatment. Only 10%–20% of children with ITP go on to have chronic disease. In contrast, most adults who are present with ITP develop chronic disease with thrombocytopenia persisting beyond 1 year, and spontaneous recovery occurs in less than 10% of such cases. Acute and chronic ITP are approached differently and therefore are discussed in two separate chapters; acute childhood ITP will be reviewed in this chapter, whereas chronic ITP in adults will be presented in Chapter 102 .
Pathophysiology
Although ITP is an autoimmune disease, the precise pathophysiologic mechanisms responsible for the disorder are poorly understood. A major feature of ITP is Fc receptor–mediated clearance of IgG autoantibody–coated platelets by macrophages in the reticuloendothelial system. Most affected children produce both IgG and IgM autoantibodies reactive to multiple platelet antigens, usually platelet surface glycoproteins such as GPIIb/IIIa and GPIb/IX. However, not all patients have measurable antibodies, and the mechanisms that trigger autoantibody production are not clear. Children with acute ITP show increased expression of gamma interferon–dependent genes in the early stages of the disease, indicating the presence of a global proinflammatory state. T-cell abnormalities are also involved in the pathophysiology of acute ITP. Imbalances in the mutually inhibitory Th1 and Th2 patterns of cytokine response in T-helper lymphocytes have been measured in patients with ITP. Platelet autoreactive T-cell clones have been identified in the peripheral blood of children with ITP, and cytotoxic T cells from ITP patients can destroy platelets with a high effector cell to target ratio. In addition, abnormalities in the numbers and function of regulatory T cells (CD4 + , CD25 + T cells) have been shown to be important for the development of many autoimmune diseases, including ITP. Ultimately, the normal mechanisms of self-tolerance and autoantibody suppression are reestablished in the majority of children with ITP, and the thrombocytopenia resolves.
Clinical Manifestations
The physical findings of ITP are usually limited to those associated with thrombocytopenia and include petechiae, bruising, and mucocutaneous bleeding. Patients with acute ITP usually have a rapid onset of bleeding symptoms, which appear over a few hours or days. Typically, children with ITP have surprisingly few other complaints. There may be a history of a recent upper respiratory infection, febrile illness, or immunization, but the history is otherwise unremarkable. In the majority of children with ITP, there is no history of persistent fevers, recurrent infection, weight loss, bone pain, fatigue, or other constitutional symptoms. Despite severe thrombocytopenia in the majority of cases, there is a surprisingly low incidence of overt or severe bleeding. Occasionally children with ITP develop nasal or oral bleeding, but more serious or life-threatening bleeding is unusual. The most serious complication of acute ITP is intracranial hemorrhage (ICH). Although ICH (and other serious bleeding) does occur in childhood ITP, the risk is low (approximately 1:600). Some children with ITP will have other findings, such as fever, lymphadenopathy, or splenomegaly, but these findings are atypical and deserve further scrutiny for a more serious condition such as leukemia, myelodysplasia, rheumatologic disorder, or infection.
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