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Meta-analysis identifies predictors of chronic childhood immune thrombocytopenia
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Female gender, older age at presentation and the presence of antinuclear antibodies were among the characteristics that predicted chronic immune thrombocytopenia in children, according to results of a meta-analysis.
Researchers also observed a considerable protective effect of IV immunoglobulin alone against chronic immune thrombocytopenia.
Katja M.J. Heitink-Pollé, MD, of University Medical Center Utrecht and Wilhelmina Children’s Hospital in the Netherlands, and colleagues reviewed data from 54 studies conducted between 1975 and 2013. All studies included children aged 3 months to 18 years who were newly diagnosed with immune thrombocytopenia. The number of children in each study ranged from 43 to 1,984.
Chronic immune thrombocytopenia — or thrombocytopenia ˂100 x 109/L for more than 12 months — occurs in about 20% to 25% of cases.
When researchers reviewed the studies, they determined clinical predictors of chronic immune thrombocytopenia included female gender (OR=1.17; 95% CI, 1.04-1.31), absence of previous infections or vaccinations (OR=3.08; 95% CI, 2.19-4.32), and insidious onset of immune thrombocytopenia (OR=11.27; 95% CI, 6.27-20.27).
Age older than 11 years also was associated with chronic immune thrombocytopenia (OR=2.47; 95% CI, 1.94-3.15), and patients who developed chronic disease were a mean 2.68 years older (95% CI, 1.89-3.47) than those with disease resolution.
Researchers identified two laboratory measures — platelet counts ≥20 x 109/L at presentation (OR=2.15; 95% CI, 1.63-2.83) and the presence of antinuclear antibodies (OR=2.87; 95% CI, 1.57-5.24) — that increased risk for development of chronic immune thrombocytopenia.
Researchers determined patients treated with a combination of methylprednisolone and IV immunoglobulin were more likely to develop chronic immune thrombocytopenia (OR=2.67; 95% CI, 1.44-4.96), yet patients treated with IV immunoglobulin alone were less likely to develop chronic disease (OR=0.71 95% CI, 0.52-0.97).
“The protective effective of IV immunoglobulin is remarkable and needs confirmation in prospective randomized trials, as well as future laboratory studies to elucidate the mechanism of this effect,” Heitink-Pollé and colleagues wrote.
Patients who had mucosal bleeding at diagnosis also were less likely to develop chronic immune thrombocytopenia (OR=0.39; 95% CI, 0.28-0.54).
“The information provided by our systematic review serves the need for identification of reliable predictors for the outcome of immune thrombocytopenia and will guide researchers in the field of pediatric as well as adult immune thrombocytopenia to reflect on their own research as well as to design future studies,” the researchers concluded. “Based on our review, new prediction scores can be generated and tested in large cohorts of patients. To be able to compare prognostic risk factors, in future studies all predictors should be strictly defined and be recorded at time of diagnosis of immune thrombocytopenia. In this way, we might be able to identify patients at higher risk of developing chronic immune thrombocytopenia who may benefit from treatment to prevent a chronic course of immune thrombocytopenia.”
Disclosure: The researchers report no relevant financial disclosures.
Perspective
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Laurence A. Boxer, MD
As the authors indicate, childhood immune thrombocytopenia (ITP) is considered to be a heterogeneous disease in terms of pathophysiology and clinical course. The authors concluded from their analysis that an older age of the patient, insidious onset, lack of a preceding infection, mild bleeding or higher platelet counts could be the strongest risk factors for chronic ITP. They also suggested that IV immunoglobulin treatment might protect against development of chronic ITP. Unfortunately, the cited article provided incomplete data regarding pathophysiology.
As noted in Figure 2, patients who developed chronic ITP were aged older than 11 years compared with the younger children. Adolescents who manifest chronic ITP often have underlying immune dysfunction, such as those with Evan’s syndrome and combined variable immune deficiency. In addition, older children might have autoimmune lymphoproliferative disease underlying the predisposition to ITP. Those children with underlying disorders often prove refractory to conventional treatment with immunoglobulin and/or steroid therapy and may require immunosuppressive therapy. No mention in the article was made regarding the role of splenectomy. Future studies regarding a possible treatment need to evaluate the immune status of patients, especially adolescents, before randomized treatments with IV immunoglobulin are implemented.
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