Optimizing the management of congenital thrombotic thrombocytopenic purpura

Congenital thrombotic thrombocytopenic purpura (cTTP) is a rare, life-threatening thrombotic microangiopathy caused by genetic mutations in the ADAMTS-13 gene, leading to severe enzyme deficiency. This results in the accumulation of ultralarge von Willebrand factor multimers, which trigger platelet aggregation, microangiopathic hemolytic anemia, thrombocytopenia, and organ damage. cTTP episodes are often triggered by physiological stressors and have a bimodal age of presentation.

To summarize the clinical course, complications, and advances in treatment of cTTP, highlighting the role of recombinant ADAMTS-13 (rADAMTS-13).

A review of registry data, clinical studies, and expert guidelines was conducted to assess cTTP pathophysiology, presentation, and therapeutic approaches.

Acute cTTP episodes manifest variably, often requiring a "second hit," such as infection or pregnancy, for disease induction. Chronic complications include cardiovascular disease, chronic kidney disease, and neurocognitive impairments, contributing to increased morbidity and mortality. Plasma infusions are effective but are associated with logistical challenges and adverse events. rADAMTS-13, a novel therapy approved in 2023, demonstrated superior efficacy in preventing acute episodes and reducing treatment burden, with fewer adverse events compared with standard plasma therapy.

cTTP management necessitates individualized care by a multidisciplinary team. Treatment of cTTP relies on ADAMTS-13 replacement, which may be more effectively delivered with rADAMTS-13 than with plasma infusions. Further studies are needed to evaluate its long-term safety, particularly during pregnancy, and to optimize treatment strategies.