PO129 | CLINICAL BENEFIT OF RECOMBINANT ADAMTS13 IN CTTP ASSOCIATED WITH HOMOZYGOUS PD173G MUTATION AND UNDETECTABLE ACTIVITY

Abstract

Background. Congenital thrombotic thrombocytopenic purpura (cTTP) is a rare hereditary disorder caused by severe deficiency of the ADAMTS13 enzyme, leading to recurrent thrombotic microangiopathy. We report the case of a 34-year-old male with homozygous missense mutation p.D173G, associated with 0% ADAMTS13 activity, diagnosed after presenting with thrombocytopenia, hemolytic anemia, and neurological risk features. Family history revealed consanguinity and a sibling death from similar manifestations, supporting a genetic etiology.Methods. Clinical history, laboratory findings, genetic analysis, and therapeutic interventions were reviewed. The patient previously received on-demand Fresh Frozen Plasma (FFP) infusions for acute episodes, with increasing frequency (4–5/year) and declining tolerability. Over the past 3 months, a prophylactic regimen with recombinant ADAMTS13 (rADAMTS13, provided by Takeda) was initiated at 40 U/kg intravenously every 2 weeks. Clinical response, adverse events, and episode recurrence were monitored.Results. Before prophylaxis, episodes were frequently triggered by respiratory infections and required hospitalization, with delayed platelet recovery and adverse reactions to FFP, including respiratory distress and cutaneous reactions. Following initiation of rADAMTS13, the patient experienced no cTTP relapses over 3 months, always showing ADAMTS13 levels at trough>5% (Fig. 1). Notably, even during bronchitis episodes, historically associated with disease flares, platelet counts remained stable, and no symptoms of microangiopathy occurred. Intravenous administration was well tolerated, with no infusion-related or systemic adverse events observed.Discussion. This case highlights the clinical burden of recurrent cTTP and limitations of FFP therapy, including adverse reactions and suboptimal efficacy over time. Prophylactic rADAMTS13 appears to provide sustained enzymatic replacement of ADAMTS13, never observed at a level <5% (Fig. 1), preventing trigger-induced relapses. The favorable safety profile and effectiveness observed in this patient align with emerging evidence supporting recombinant therapy as a disease-modifying strategy.Conclusions. Prophylactic recombinant ADAMTS13 demonstrated excellent short-term efficacy and safety in a patient with cTTP due to homozygous p.D173G mutation associated with absent enzymatic activity. This approach may represent a superior alternative to plasma-based therapy, particularly in patients with frequent relapses or intolerance to FFP. Longer follow-up is warranted to confirm durability of response.