A case series of pediatric patients with congenital thrombotic thrombocytopenia purpura (cTTP) treated with recombinant ADAMTS13 Free

Congenital thrombotic thrombocytopenic purpura (cTTP), also known as Upshaw-Schulman Syndrome, is an ultra-rare thrombotic microangiopathy caused by inherited deficiency of ADAMTS13 (A Disintegrin and Metalloproteinase with Thrombospondin type 1 motif, member 13) with <10% activity. ADAMTS13 is a von Willebrand factor-cleaving metalloprotease; its deficiency results in accumulation of large von Willebrand multimers with high platelet-binding activity (Sukumar 2021, Sadler 2017). This leads to circulating platelet-rich microthrombi and subsequent organ ischemia (Sukumar 2021), potentially causing irreversible complications. Until recently, treatment of cTTP centered on ADAMTS13 replacement through frozen plasma (FFP) or plasma-derived factor VIII-von Willebrand factor concentrates (Alwan 2019, Scully 2024). In 2023, a recombinant ADAMTS13 product (rADAMTS13), received FDA approval. While this therapy has shown promising outcomes in reducing complications and flares, only four children under age 6 were included in the original analysis (Scully 2024). Real world pediatric data supporting the use of rADAMTS13 is limited (Sakai 2025, Laguna 2025).

Our case series aims to describe the clinical presentation, laboratory findings and treatment response in three young children with cTTP. The overall goal is to provide real world evidence supporting the safety and efficacy of recombinant ADAMTS13 in young children.

With parental consent, we conducted a retrospective analysis of three pediatric patients, each presenting with at least two features consistent with TTP, low ADAMTS13 activity, and genetically confirmed mutations. Patients were treated according to the standard of care (FFP or rADAMTS13). In addition to clinical evaluation, treatment response was monitored via hemoglobin, platelet count, bilirubin, and serum creatinine levels.

Results:Patient 1 presented at 8 months of age with flu-like symptoms, petechiae, bruising, and jaundice. Laboratory testing at diagnosis was notable for a hemoglobin of 9.3 g/dL with evidence of hemolysis (LDH 2075 U/L, indirect hyperbilirubinemia to 1.8 mg/dL), thrombocytopenia with a platelet count of 5 X 10³/mcL, and creatinine 0.43 gm/dL. ADAMTS13 activity was <5% with a confirmed ADAMTS13 c.703G>T (p.Asp235Tyr) mutation. He started rADAMTS13 at 40IU/kg every 2-week prophylaxis at 14 months of age and has received 14 lifetime infusions. Post-treatment lab testing shows a hemoglobin of 11.3 gm/dL, platelet count 300 X 10³/mcL, total bilirubin 0.3 mg/dL, and creatinine 0.38 gm/dL. He has not had any acute TTP flares or adverse reactions.

Patient 2 presented at 2 years of age with upper respiratory infection (URI) symptoms and petechiae. Laboratory testing at the time of diagnosis was notable for hemoglobin of 6.5 g/dL with evidence of hemolysis (indirect hyperbilirubinemia to 2.2 mg/dL, LDH to 1537 U/L), platelet count of 8 X10³/mcL. ADAMTS13 activity was 5%, with a confirmed ADAMTS13, c.703G>T (p.Asp235Tyr) mutation. He was started on every 2-week FFP prophylaxis and switched to rADAMTS13 (35-70 IU/kg rounded to nearest vial size) every 2 weeks prophylaxis after 1 month. Post treatment lab testing shows hemoglobin of 13.5 gm/dL, platelet count 452 X 10³/mcL, total bilirubin 0.4 mg/dL, and creatinine of 0.30 gm/dL. He has received a total of 39 total treatments without acute flares or adverse events.

Patient 3 presented at 3 years old with fever and URI symptoms. Laboratory testing showed hemoglobin of 6.6 g/dL with indirect hyperbilirubinemia to 1.27 mg/dL, and thrombocytopenia with platelet count of 12 X 10³/mcL. ADAMTS13 activity was <5% with heterozygous likely pathogenic (c.1393_1394del, p.Ala465Leufs*68) mutation. Post treatment lab testing shows hemoglobin of 12 gm/dL, platelet count 485 X 10³/mcL, total bilirubin 0.4 gm/dL, and creatinine 0.34 gm/dL. He received 8 FFP infusions prior to transition to rADAMTS-13 and has received a total of 38 treatments (35-70 IU/kg rounded to nearest vial size), without acute flares or adverse events.

All three children in our case series, two of whom were switched from FFP, have tolerated rADAMTS13 without any reactions and have not experienced any TTP flares. Lab parameters for all patients remain improved since starting treatment. Our data supports the safety and efficacy of rADAMTS13 in young children. More pediatric real-world evidence is needed and will further inform management of cTTP.