# Optimizing the management of congenital thrombotic thrombocytopenic purpura

## TL;DR

This paper reviews the management of a rare inherited blood disorder called congenital TTP, focusing on a new treatment that could improve patient outcomes.

## Contribution

The paper highlights the clinical advantages of recombinant ADAMTS-13 over traditional plasma therapy for congenital TTP.

## Key findings

- Plasma infusions are effective but have logistical challenges and adverse events.
- Recombinant ADAMTS-13 shows improved efficacy and safety for preventing acute cTTP episodes.
- Multidisciplinary care is essential for managing cTTP due to its complex complications.

## Abstract

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.

•Congenital TTP (cTTP) is a rare, inherited disorder caused by biallelic ADAMTS13 mutations, leading to recurrent microvascular thrombosis, hemolytic anemia, and organ damage.•This review draws on international hereditary TTP registries, clinical studies of plasma and recombinant ADAMTS13 therapy, and real-world patient experiences, including pregnancy management.•Plasma therapy reduces acute episodes but is burdensome and inconsistently effective, while recombinant ADAMTS13 shows improved prophylactic efficacy, safety, and convenience.•rADAMTS13 represents a major advancement in cTTP management, offering a targeted, potentially safer, and more sustainable treatment option that may improve long-term patient outcomes.

Congenital TTP (cTTP) is a rare, inherited disorder caused by biallelic ADAMTS13 mutations, leading to recurrent microvascular thrombosis, hemolytic anemia, and organ damage.

This review draws on international hereditary TTP registries, clinical studies of plasma and recombinant ADAMTS13 therapy, and real-world patient experiences, including pregnancy management.

Plasma therapy reduces acute episodes but is burdensome and inconsistently effective, while recombinant ADAMTS13 shows improved prophylactic efficacy, safety, and convenience.

rADAMTS13 represents a major advancement in cTTP management, offering a targeted, potentially safer, and more sustainable treatment option that may improve long-term patient outcomes.