Idiopathic thrombocytopenic purpura in childhood : Clinical features, diagnostics and treatment

University dissertation from Stockholm : Karolinska Institutet, Karolinska Institutet, Stockholm Söder Hospital

Abstract: Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by thrombocytopenia, i.e. platelet count (pl.c.) <150x109/L, due to antibody binding to platelet antigen(s) causing their rapid destruction by the reticuloendothelial system, especially the spleen. Acute onset ITP often follows a viral illness or immunization, and in the majority of children the disorder resolves within 6 months. Some 15-25% develop a chronic form of ITP. The literature shows that the investigation and management of children with ITP vary widely, and is not evidence based due to lack of clinical trials. There are few randomized trials in ITP and many of the recommendations for the management of childhood ITP are based on expert opinion. The aims of the present studies were to evaluate a promising treatment (at the time) for chronic ITP, pulsed high-dose dexamethasone, and its possible effects on the immune system. We further wanted to study the course, management and morbidity of ITP during the first 6 months after diagnosis. A randomized study where the children were assigned at random (2:1) to treatment with dexamethasone or IVIg for six months, and then followed for six additional months was conducted. The T cell receptor (TCR) repertoires of CD4+ and CD8+ peripheral blood lymphocytes of 16 patients were analysed by staining with a panel of anti-TCR Valpha and VP antibodies followed by flow cytometry. Pulsed high-dose dexamethasone treatment induced long term partial or complete response in 25% of treated patients, as measured by the platelet counts. Side-effects were common and in some cases led to discontinuation of the treatment. Overall T cell expansion frequency was the same in the children with chronic ITP as in healthy individuals. However, the presence of expansions that normalized with treatment suggests that T cells may play a role the pathogenesis of ITP. All pediatric departments in the five Nordic countries were asked to include all children aged 0-14, with newly diagnosed ITP and at least one recorded pl.c. below 30 x 109/L, in a study performed between January 1, 1998 and December 31, 2000. 501 children from 97 institutions were included. The study has established that ITP takes a short and uneventful course in the great majority of children, that the morbidity is limited even in children with prolonged or persisting disease, and that bleeding episodes requiring specific treatment such as blood transfusions are rare. A majority of the children received treatment within 14 days of diagnosis. A high treatment rate reduced the exposure to risk as reflected by more frequent early termination of the period with pl.c. <20 x 109/L. It did not, however, reduce the duration of disease or the frequency of chronic course. It also failed to reduce the morbidity from disease during 6 months follow up. Morbidity from disease-related events occurred mainly in children with chronic ITP and was very low in children with acute ITP. Finally, the total burden of disease was assessed from the sum of events, interventions and complications in the patientgroups, assuming that procedures are stressful as well as bleeding events. The total number of interventions vastly exceeded the number of bleeding events, especially for children with acute ITP admitted to centers with high treatment rates.

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