Abstract
Introduction: Immune thrombotic thrombocytopenic purpura (iTTP) in children is a rare form of thrombotic microangiopathy characterized by severe ADAMTS13 deficiency. While caplacizumab has demonstrated efficacy in adults with iTTP, data on its safety and effectiveness in pediatric populations remain limited. Current approvals for pediatric use vary across regulatory agencies, and pediatric patients were excluded from pivotal trials. This scoping review aims to synthesize published evidence on the use of caplacizumab in children with iTTP.
Methods: This scoping review was conducted in accordance with PRISMA guidelines. A systematic search of PubMed and Scopus was performed from database inception through June 2025 to identify studies reporting clinical data on pediatric patients (<18 years) with immune-mediated thrombotic thrombocytopenic purpura (iTTP) treated with caplacizumab. Eligible studies included case reports, case series, and cohort studies involving patients with confirmed iTTP, defined by ADAMTS13 activity <10% and the presence of an ADAMTS13 inhibitor, who received caplacizumab. Extracted data included demographics, clinical presentation, laboratory findings, treatment details, adverse events, and outcomes. Numerical data were reported as medians or means, as appropriate. Percentages were calculated using available denominators, excluding cases with missing data.
Results: Fifteen publications (14 case reports/series and one cohort study) were included, encompassing 36 pediatric patients. The median age was 14 years (range 1–17), with 22% under 12 years. Females comprised 72% (n=26). Neurological symptoms on presentation were reported in 53%, bleeding manifestations in 74%, and renal impairment in 26%. Most patients exhibited classical laboratory features of iTTP: median platelet count 9×10⁹/L, hemoglobin 7 g/dL, schistocytes in 89% of reported smears, and elevated LDH (median 1788 U/L). Troponin was elevated in 77% of reported cases.
Caplacizumab was administered at 10 mg in 75%, 5 mg in 17%, and 11 mg in 8% of patients. Among children under 12 years, 75% received 5 mg. Median treatment duration was 33.5 days (range 14–97). Corticosteroids and rituximab were given in 97% and 92% of patients, respectively. Plasma exchange (TPE) was used in most cases, with 22% receiving >10 sessions.
In terms of efficacy, the median time to platelet count normalization after caplacizumab initiation was 3.5 days (range 2–10), with 80% achieving rapid recovery (within four days). Median hospital stay was 14 days (range 7–90). The mean time to ADAMTS13 recovery was 38.5 days. Notably, all patients demonstrated clinical response, including those treated for severe, refractory, or recurrent TTP. Two patients (6%) relapsed during follow-up; the remaining 94% remained relapse-free. All 36 patients survived. Among three patients with persistently low ADAMTS13 activity, two responded to rituximab, while one required immunoadsorption. These findings suggest potential benefit of caplacizumab even in complex or treatment-resistant cases.
Regarding safety, adverse events were infrequent and generally mild. No major or life-threatening bleeding events were reported. Minor bleeding occurred in 11%, with epistaxis, hematuria, and injection site reactions each in 6%. One case of jugular venous thrombosis was documented but not clearly attributed to treatment. In 36% of patients, no adverse events were reported. In 33% of cases, adverse events were not specified, which limits comprehensive assessment. Overall, available data suggest a favorable safety profile in children.
Conclusion:Caplacizumab appears to be both effective and well-tolerated in pediatric iTTP. It was associated with rapid platelet recovery, relatively short hospitalization, and high remission rates, with no reported treatment-related deaths or major bleeding. Notably, many patients were treated off-label below the EMA-approved age or weight thresholds, highlighting the clinical need despite regulatory limitations. Treatment duration and dosing varied across cases, reflecting the absence of standardized pediatric protocols. Long-term data remain sparse, and heterogeneity in reporting limits definitive conclusions. These findings support further investigation of caplacizumab in children through prospective pediatric-specific studies and registries to optimize dosing, monitor long-term safety, and define its role in treatment algorithms.
