Clinical and laboratory predictors of chronic immune thrombocytopenia in children: a systematic review and meta-analysis

Abstract

Key Points• Older age, insidious onset, no preceding infection, mild bleeding, and higher platelet count are the strongest risk factors for chronic ITP.• Intravenous immunoglobulin treatment seems to protect against development of chronic ITP.Childhood immune thrombocytopenia (ITP) is a rare autoimmune bleeding disorder. Most children recover within 6 to 12 months, but individual course is difficult to predict. We performed a systematic review and meta-analysis to identify predictors of chronic ITP. We found 1399 articles; after critical appraisal, 54 studies were included. The following predictors of chronic ITP in children, assessed in at least 3 studies, have been identified: female gender (odds ratio [OR] 1.17, 95% confidence interval [CI] 1.04-1.31), older age at presentation (age ‡11 years; OR 2.47, 95% CI 1.94-3.15), no preceding infection or vaccination (OR 3.08,, insidious onset (OR 11.27,), higher platelet counts at presentation ( ‡20 3 10 9 /L: OR 2.15, 95% CI 1.63-2.83), presence of antinuclear antibodies (OR 2.87, 95% 1.57-5.24), and treatment with a combination of methylprednisolone and intravenous immunoglobulin (OR 2.67, 95% CI 1. 44-4.96). Children with mucosal bleeding at diagnosis or treatment with intravenous immunoglobulin alone developed chronic ITP less often (OR 0.39, 95% CI 0.28-0.54 and OR 0.71, 95% CI 0.52-0.97, respectively). The protective effect of intravenous immunoglobulin is remarkable and needs confirmation in prospective randomized trials as well as future laboratory studies to elucidate the mechanism of this effect. (Blood. 2014;124(22):3295-3307) IntroductionChildhood immune thrombocytopenia (ITP) is a rare autoimmune disorder characterized by isolated thrombocytopenia (peripheral blood platelet count ,100 3 10 9 /L) in the absence of other causes that may be associated with thrombocytopenia.1 Most children present with a typical history of acute development of purpura and bruising, often after a mild viral infection. Management of newly diagnosed ITP consists of careful observation, regardless of platelet count. Severe bleeding, occurring in only 3% to 5% of children, 2 requires treatment with corticosteroids, intravenous immunoglobulin (IVIg), or anti-Rhesus-D immunoglobulin, either alone or in combination and, if life threatening, also with platelet and red blood cell transfusions. 3,4 Chronic ITP is currently defined as thrombocytopenia ,100 3 10 9 /L lasting for .12 months.1 About 20% to 25% of children with newly diagnosed ITP will develop chronic disease. Because of the high impact of ITP on a child's everyday life and activities, as well as to decide whether treatment has to be instituted to influence the clinical course of ITP, it is of clinical significance if the course of the disease could be predicted at time of diagnosis.Several clinical, therapeutic, laboratory, and genetic predictors of chronic ITP have been evaluated in children.5-7 A systematic review or meta-analysis, however, has not yet been performed. In this study, we systematically analyzed all...

Clinical course and prognostic factors of childhood immune thrombocytopenia: single center experience of 10 years

“…A recent comprehensive systematic review and meta-analysis by Heitink-Polle et al17) assessing predictors of chronic ITP in children observed an apparent protective effect of IVIG treatment against the development of chronic disease. Thus, since all of our patients who required treatment for ITP (70.3% of our total patient population) received IVIG, our use of IVIG as first-line therapy might have influenced the course of ITP in our study, namely our high proportion of patients with final diagnosis of acute ITP.…”

Management of newly diagnosed immune thrombocytopenia: can we change outcomes?

“…Nevertheless, modifiable disease factors that could reduce the likelihood of chronic disease in children have been sought. In a systematic review, 41 the only modifiable variable was administration of IVIg at diagnosis. The investigators have since completed a randomized prospective trial of IVIg compared with placebo for newly diagnosed children with ITP (n 5 200).…”

Spotlight on romiplostim in the treatment of children with chronic immune thrombocytopenia: design, development, and potential place in therapy

“…Despite the fact that the vast majority of children with ITP will experience resolution, estimates suggest that one-third of children will demonstrate thrombocytopenia at 12 months post-diagnosis consistent with chronic ITP 3. Risk factors associated with the development of chronic ITP in children are numerous such as female gender, older age at presentation, a lack of preceding infection or vaccination, insidious onset, higher platelet counts at presentation, and the presence of antinuclear antibodies 4. Other biomarkers such as cytokines and gene expression profiles are currently being explored to better differentiate chronic ITP from those newly diagnosed cases that will not become chronic 5,6.…”