Retrospective Epidemiological Study of Patients in the National Cohort of the French TMA Center

The TWI-LIGHT protocol is a retrospective, non-interventional epidemiological study coordinated by the French National Reference Center for Thrombotic Microangiopathies (CNR-MAT). It leverages the CNR-MAT registry to analyze long-term outcomes in over 1,200 patients diagnosed with autoimmune thrombotic thrombocytopenic purpura (iTTP) between October 1, 2000, and June 1, 2024.

Background and Rationale iTTP is a rare, life-threatening disorder caused by severe ADAMTS13 deficiency, leading to microvascular thrombosis, multiorgan damage, and high mortality without prompt treatment. Survivors face long-term risks, including cardiovascular complications, cognitive impairment, and reduced life expectancy. Despite therapeutic advances (e.g., caplacizumab, rituximab), data on late complications, risk factors, and disease burden in underrepresented subgroups (e.g., pregnant women, children, elderly patients) remain limited. This study addresses critical gaps in understanding iTTP's natural history, treatment efficacy, and survival.

Study Design

• Type: Retrospective, multicenter, non-interventional (MR-004 compliance).
• Data Collected:

• Acute Phase: Clinical presentation, lab results (standard biology, including ADAMTS13 activity, troponin), treatments (plasma exchange, immunosuppressants, caplacizumab).
• Long-Term Follow-Up: Cardiovascular events (major adverse cardiovascular events, including ischemic stroke, myocardial infarction and angioplasty) and cardiovascular risk factors (hypertension, diabetes, weight and body mass index, dyslipidemia, smoking), ADAMTS13 activity trends, neurocognitive outcomes (quality-of-life scales: SF36, HADS), relapse rates, and mortality.
• Biobanking: ADAMTS13 samples stored at Hôpital Lariboisière (Prof. Veyradier's lab) under ethical approval (AC-2023-6021).

Expected Outcomes and Impact

• Clinical Insights:

• Personalized cardiovascular risk profiles for iTTP survivors.
• Evidence-based guidelines for pregnancy, elderly, and pediatric iTTP management.
• Optimization of long-term monitoring (e.g., rituximab frequency).
• Health System Impact:

• Cost-benefit analysis of novel therapies (e.g., caplacizumab, recombinant ADAMTS13).
• Strategies to reduce diagnostic delays and hospitalizations. Real-World Relevance: Focus on underrepresented groups and long-term survival, with the goal to improve life expectancy of iTTP patients. This protocol represents a landmark effort to transform iTTP management through comprehensive real-world data, directly impacting clinical practice.
• Methodological Rigor: Centralized data auditing, ISO/IEC 17025-compliant biobanking.

Inclusion criteria

-Patients with a diagnosis of immune mediated TTP

Exclusion criteria

• Cancer- associated iTTP and HIV-associated iTTP
• Severe sepsis
• Disseminated intravascular coagulation with consumption of coagulation factors;
• Transplant-associated TTP
• HIV-associated TTP (AIDS stage)
• Patient not affiliated with a social security scheme
• Patient or parent's objection to the reuse of their healthcare data for research