Congenital TTP: Case Report and Literature Review

Background: Congenital thrombotic thrombocytopenic purpura (cTTP) is an extremely rare disease caused by an inherited deficiency of ADAMTS13. Residual ADAMTS13 activity <3% is associated with earlier disease onset and the need for prophylactic treatment. cTTP is often misdiagnosed, particularly in childhood and the neonatal period. Prompt diagnosis and treatment reduce mortality. Methods: We report the clinical manifestations, laboratory findings, genetic analysis, and treatment of a child with cTTP. Results: A six-hour-old girl developed jaundice and sudden thrombocytopenia with bleeding. She was treated with steroids, two daily exsanguinotransfusions, platelet transfusions, and phototherapy. Plasma ADAMTS13 activity was severely deficient without inhibitory antibodies. Genetic analysis revealed a compound heterozygous mutation in the ADAMTS13 gene. Daily fresh frozen plasma (FFP) infusions normalized platelet counts and hemolysis indices. Prophylactic plasma infusions were scheduled every 21 days. Despite prophylaxis, the child experienced multiple disease relapses after infectious episodes, requiring hospitalization and daily plasma infusions, sometimes complicated by infection or thrombosis related to venous access. Following ethics committee approval, recombinant ADAMTS13 was administered at 40 IU/kg every two weeks. After one year of treatment, the child experienced no disease recurrence and no infusion-related adverse events. No anti-ADAMTS13 antibodies were detected. Discussion: cTTP is a very rare disease, often misdiagnosed, with high neonatal mortality. Children frequently experience recurrent TTP triggered by infections. Prophylactic ADAMTS13 replacement should be considered to reduce disease recurrence. Recombinant ADAMTS13 appears to be a promising, effective, and safe therapeutic option.