Misdiagnosed thrombocytopenia in children and adolescents: analysis of the Pediatric and Adult Registry on Chronic ITP

Abstract

Primary immune thrombocytopenia (ITP) in children is a diagnosis of exclusion, but cases of secondary ITP and nonimmune thrombocytopenia (non-IT) are generally difficult to recognize in a timely fashion. We describe a pediatric population with a revised diagnosis of secondary ITP or non-IT within 24 months of follow-up. Data were extracted from the Pediatric and Adult Registry on Chronic ITP, an international multicenter registry collecting data prospectively in patients with newly diagnosed primary ITP. Between 2004 and 2019, a total of 3974 children aged 3 months to 16 years were included. Secondary ITP and non-IT were reported in 113 patients (63 female subjects). Infectious (n = 53) and autoimmune (n = 42) diseases were identified as the main causes, with median ages at diagnosis of 3.2 years (interquartile range: 1.2; 6.7 years) and 12.4 years (interquartile range: 7.6; 13.7 years), respectively. Other causes included malignancies, aplastic anemia, immunodeficiency, and drug use. Patients with malignancy and aplastic anemia had significantly higher initial platelet counts (37 and 52 × 109/L) than did those with infection or autoimmune diseases (12 and 13 × 109/L). Characteristics of patients with secondary ITP due to infection were similar to those of children with primary ITP at first presentation, indicating similar mechanisms. Significant differences were found for age, sex, comorbidities, initial bleeding, sustained need for treatment, and disease persistence for the remaining noninfectious group compared with primary ITP. Based on our findings, we propose a diagnostic algorithm that may serve as a basis for further discussion and prospective trials.

Graphical abstract

Figure 1.

Flowchart of patient selection. FU, follow-up.

Figure 2.

Causes of secondary ITP or non-IT in children misdiagnosed with primary ITP. Infection: HIV, n = 5; Chagas disease, n = 1; herpes zoster, n = 1; no information, n = 47. Autoimmunity: systemic lupus erythematosus, n = 16; Evans syndrome, n = 11; autoimmune lymphoproliferative syndrome, n = 2; autoimmune bicytopenia (thrombocytopenia and neutropenia), n = 5; mixed connective tissue disease, n = 2; diabetes mellitus type 1, n = 1; scleroderma, n = 1; no information, n = 4. Malignancy: myelodysplastic syndrome, n = 3; Hodgkin lymphoma, n = 1; myeloproliferative disease, n = 2; no information, n = 1. Immunodeficiency: DiGeorge syndrome, n = 1; primary chronic granulomatous disease, n = 1; not determined, n = 2.

Figure 3.

Proposal of a diagnostic algorithm for pediatric secondary ITP and non-IT. Red flags (or risk factors) are defined as female sex, age >10 years, moderate thrombocytopenia >20 × 10⁹/L, positive family history, comorbidities, and nonresponse to first-line treatment. CMV, cytomegalovirus; EBV, Epstein-Barr virus; HCV, hepatitis C virus.