Immune thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening disorder characterized by microangiopathic hemolytic anemia, severe thrombocytopenia, and ischemic organ damage due to microvascular thrombosis. It results from a severe deficiency in the von Willeband factor (vWF)-cleaving protease ADAMTS13, primarily caused by autoantibodies that inhibit its activity. This deficiency leads to accumulation of ultra-large vWF multimers, triggering pathological platelet aggregation and widespread microthrombi. iTTP typically presents with acute neurological symptoms (e.g., confusion, seizures, coma), cardiac events (e.g., myocardial infarction), and multiorgan dysfunction. Without prompt treatment-plasma exchange, immunosuppression, and the vWF inhibitor caplacizumab-mortality exceeds 90%. Survivors face long-term risks, including cardiovascular complications, cognitive impairment, and reduced life expectancy.
The TWI-LIGHT protocol is a national retrospective epidemiological study coordinated by the French Reference Center for Thrombotic Microangiopathies (CNR-MAT). It aims to analyze long-term outcome in \>1,200 iTTP patients diagnosed between October 2000 and June 2024. The study leverages pseudonymized data from the CNR-MAT registry, collected via a secure REDCap database.
Key Objectives:
1. Primary: Assess the impact of cardiovascular risk factors (e.g., hypertension, diabetes) and ADAMTS13 activity on life expectancy in iTTP survivors. 2. Secondary:
* Evaluate disease burden in underrepresented groups (pregnant/postpartum women, children, elderly patients). * Analyze the influence of new therapies (caplacizumab, rituximab, recombinant ADAMTS13) on care pathways. * Identify prognostic factors and treatment practices. * Characterize neurocognitive outcomes and quality of life post-iTTP.
Methodology:
* Design: Non-interventional, retrospective (MR-004 compliance), using data from standard care. * Inclusion: Patients with confirmed iTTP (thrombocytopenia, hemolytic anemia, ADAMTS13 \<10%), diagnosed within the study period, and ≥1 year of follow-up. * Exclusion: Cancer-associated iTTP, severe sepsis, or patient opposition to data reuse. * Data Collection: Clinical, biological, and therapeutic variables from hospital/consultation records, including cardiovascular events, ADAMTS13 activity, and neurocognitive assessments. * Analysis: Kaplan-Meier survival curves and Cox regression models to identify risk factors for non-iTTP-related death.
Expected Outcomes:
* Prevalence of cardiovascular comorbidities and their correlation with ADAMTS13 activity. * Insights into iTTP subtypes (e.g., gestational, pediatric) and therapeutic efficacy. * Evidence-based strategies for personalized long-term management.
Ethical Framework:
* AP-HP-sponsored, with oversight from Sorbonne University's ethics committee. * Patients informed of data reuse with opt-out rights; data archived for 15 years.
This landmark study will inform clinical guidelines, optimize survivor care, and address unmet needs in iTTP management through comprehensive, real-world data analysis.
None
Cancer- associated iTTP and HIV-associated iTTP
Severe sepsis
Disseminated intravascular coagulation with consumption of coagulation factors;
Transplant-associated TTP
The study population consists of all patients in France diagnosed with thrombotic thrombocytopenic purpura (TTP), primarily the autoimmune subtype, between October 1, 2000, and June 1, 2024, who received care within the national network of the French Reference Center for Thrombotic Microangiopathies (CNR-MAT). This includes adults and children with autoimmune who have at least one year of follow-up. Patients are recruited from 6 core and 25 competence centers covering mainland France and overseas territories, ensuring nationwide representation. Data are collected from hospital and consultation records, and only patients who do not object to data reuse are included. This approach ensures a comprehensive, multicentric, and representative cohort for rare disease research.
Cohort
Retrospective
Not listed
prevalence of major cardiovascular events
ischemic strocke, myocardial infarction, reperfusion/angioplasty
Incidence of cardiovascular risk factors
Hypertension, diabetes, dyslipidaemia, smocking, body mass index,
correlation between ADMTS13 activity during remission and incidence of cardiovascular events and life expectancy
characterization of pregnancy onset iTTP
clinical presentation, management, prognosis(specific characteristics )
characterization of childhood onset iTTP
clinical presentation, management, prognosis(specific characteristics )
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