Background In childhood immune thrombocytopenia (ITP), an autoimmune bleeding disorder, there is a need for better prediction of individual disease courses and treatment outcomes.Objective To... Show moreBackground In childhood immune thrombocytopenia (ITP), an autoimmune bleeding disorder, there is a need for better prediction of individual disease courses and treatment outcomes.Objective To predict the response to intravenous immunoglobulins (IVIg) and ITP disease course using genetic and immune markers.Methods Children aged younger than 7 years with newly diagnosed ITP (N = 147) from the Treatment With or Without IVIG for Kids with ITP study were included, which randomized children to an IVIg or observation group. A total of 46 variables were available: clinical characteristics, targeted genotyping, lymphocyte immune phenotyping, and platelet autoantibodies.Results In the treatment arm, 48/80 children (60%) showed a complete response (platelets >= 100 x 10(9)/L) that lasted for at least 1 month (complete sustained response [CSR]) and 32 exhibited no or a temporary response (absence of a sustained response [ASR]). For a biological risk score, five variables were selected by regularized logistic regression that predicted ASR vs CSR: (1) hemoglobin; (2) platelet count; (3) genetic polymorphisms of Fc-receptor (Fc gamma R) IIc; (4) the presence of immunoglobulin G (IgG) anti-platelet antibodies; and (5) preceding vaccination. The ASR sensitivity was 0.91 (95% confidence interval, 0.80-1.00) and specificity was 0.67 (95% confidence interval, 0.53-0.80). In the 67 patients of the observation arm, this biological score was also associated with recovery during 1 year of follow-up. The addition of the biological score to a predefined clinical score further improved the discrimination of favorable ITP disease courses.Conclusions The prediction of disease courses and IVIg treatment responses in ITP is improved by using both clinical and biological stratification. Show less
Schmidt, D.E.; Edslev, P.W.; Heitink-Polle, K.M.J.; Mertens, B.; Bruin, M.C.A.; Kapur, R.; ... ; Haas, M. de 2020
Background Childhood immune thrombocytopenia (ITP) is an autoimmune bleeding disorder. The prognosis (transient, persistent, or chronic ITP) remains difficult to predict. The morbidity is most... Show moreBackground Childhood immune thrombocytopenia (ITP) is an autoimmune bleeding disorder. The prognosis (transient, persistent, or chronic ITP) remains difficult to predict. The morbidity is most pronounced in children with persistent and chronic ITP. Clinical characteristics are associated with ITP outcomes, but there are no validated multivariate prediction models.Objective Development and external validatation of the Childhood ITP Recovery Score to predict transient versus persistent ITP in children with newly diagnosed ITP.Methods Patients with a diagnosis platelet count <= 20 x 10(9)/L and age below 16 years were included from two prospective multicenter studies (NOPHO ITP study, N = 377 [development cohort]; TIKI trial, N = 194 [external validation]). The primary outcome was transient ITP (complete recovery with platelets >= 100 x 10(9)/L 3 months after diagnosis) versus persistent ITP. Age, sex, mucosal bleeding, preceding infection/vaccination, insidious onset, and diagnosis platelet count were used as predictors.Results In external validation, the score predicted transient versus persistent ITP at 3 months follow-up with an area under the receiver operating characteristic curve of 0.71. In patients predicted to have a high chance of recovery, we observed 85%, 90%, and 95% recovered 3, 6, and 12 months after the diagnosis. For patients predicted to have a low chance of recovery, this was 32%, 46%, and 71%. The score also predicted cessation of bleeding symptoms and the response to intravenous immunoglobulins (IVIg).Conclusion The Childhood ITP Recovery Score predicts prognosis and may be useful to individualize clinical management. In future research, the additional predictive value of biomarkers can be compared to this score. A risk calculator is available (). Show less
Zwaginga, J.J.; Holt, B. van der; Boekhorst, P.A. te; Biemond, B.J.; Levin, M.D.; Griend, R. van der; ... ; Dutch HOVON 64 Study Grp 2015
