P138 | USE OF CAPLACIZUMAB IN CONGENITAL THROMBOTIC THROMBOCYTOPENIC PURPURA IN CLINICAL PRACTICE

Congenital thrombotic thrombocytopenic purpura (cTTP) is an ultra-rare thrombotic microangiopathy caused by inherited deficiency of ADAMTS13, the metalloprotease responsible for cleaving von Willebrand factor (VWF). This enzymatic defect results in the accumulation of ultra-large VWF multimers, predisposing to microvascular thrombosis. Clinical presentation usually occurs in neonatal period or childhood, more rarely in adults, especially during pregnancy. Treatment involves support with fresh frozen plasma transfusions to normalize ADAMTS13 levels. Caplacizumab, an anti-VWF antibody, is approved for the treatment of acquired TTP and the use in congenital forms should be considered off-label in selected cases with severe clinical manifestations. We report the case of a 74-year-old woman presenting with acute dysarthria and right-sided facial palsy. Neuroimaging revealed an ischemic stroke. Laboratory tests showed thrombocytopenia (platelet count 66 × 10³/µL), elevated LDH, schistocytes on peripheral smear (5%), reduced haptoglobin and suppressed ADAMTS13 activity with no detectable inhibitor. Thrombotic thrombocytopenic purpura was suspected, so the patient was treated with plasma exchange and Caplacizumab with rapid hematologic response and normalization of platelet count (375 x 10³/µL). Given the absence of autoantibodies, a medical history of previous ischemic stroke and recurrent pregnancy loss and persistent ADAMTS13 deficiency, genetic testing was performed. Two ADAMTS13 variants ware detected: c.1883A>G (p.Tyr628Cys, novel) and c.3251G>A (p.Cys1084Tyr, known to be pathogenic), confirming a diagnosis of cTTP. Following molecular confirmation, Caplacizumab was discontinued and plasma therapy initiated as per guidelines for congenital forms. Unfortunately, after the first infusion, the patient developed pneumonia, triggering a reactivation of thrombotic microangiopathy and resulting in a fatal outcome. This case highlights the therapeutic potential of Caplacizumab in congenital forms to a rapid clinical and hematologic improvement, reducing both the number of plasma exchange sessions and ICU stay. Although off-label, Caplacizumab may represent a valuable option in selected cTTP patients with severe manifestations or refractory to the standard procedures. Further studies to define its role in congenital TTP management are warranted.