Congenital Thrombotic Thrombocytopenic Purpura (cTTP) – Case report of two siblings

Introduction cTTP belongs to the group of thrombotic microangiopathies and is characterized by the congenital absence of the enzyme ADAMTS 13, the von Willebrand Factor-cleaving protease. The diagnosis of this very rare, life-threatening disease is often delayed resulting in a severe, possibly even lethal course. Unfortunately, the PLASMIC-Score is not validated for paediatric cases. The modified PLASMICkid-Score, substituting Serum-Creatinine by eGFR, is also not validated in adequate studies so far. Method We present a case report of two siblings. Results In the course of a initially uncomplicated respiratory infection which was persisting for one week and treated symptomatically, the condition of an 8.5-year-old girl deteriorated dramatically and required intensive care therapy for the suspected diagnosis of pneumonia with septic shock. In the absence of anaemia and schistocytes, moderate thrombocytopenia of 69 GPt/L, high inflammation parameters, significant increase in creatinine and conspicuous coagulation with normalisation of all laboratory parameters in the course of the disease, the diagnosis of the underlying cTTP remained undetected. The markedly elevated lactate dehydrogenase (LDH 18.3 µmol/s*L) and the subsequent development of anaemia were interpreted as connected to the severe inflammation. The retrospectively determined PLASMIC Score disclosed 4 points. Four months later, the child presented with a seizure in the presence of a gastrointestinal infection, petechial skin bleedings caused by severe thrombocytopenia (5 GPt/L) and kidney failure requiring dialysis. At this time schistocytes were detectable. Due to a PLASMIC-Score of 6, plasma exchange was carried out immediately. The markedly reduced ADAMTS 13 activity (8.4%, determined beforehand), without detectable antibodies finally led to the diagnosis of cTTP – later also confirmed by molecular genetics. Subsequently ADAMTS 13 concentrates were administered repeatedly and continued as a bi-weekly permanent substitution therapy in the outpatient setting. At time of diagnosis, her 4.5-year-old brother had been hospitalized simultaneously for 3 days due to a seizure during a viral respiratory infection. The patient was stable. The diagnosis of cTTP, suspected in context of his sister’s condition, was confirmed by schistocytes and ADAMTS 13 activity