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

NCT07205861 | Recruiting

• 1 other identifier: APHP240960
• Study Type: observational
• Target: 1,200
• Locations: 1 country
• Sites: 1

Brief Summary

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:

• 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.

Conditions

Thrombotic Thrombocytopenic Purpura (TTP); Immune Thrombotic Thrombocytopenic Purpura; Thrombotic Microangiopathies; Microangiopathy, Thromboic; Cardiovascular Diseases; Autoimmune Diseases; Rare Diseases; Neurological Manifestations

Keywords

Thrombotic Thrombocytopenic Purpura; Immune Thrombotic Thrombocytopenic Purpura; Thrombotic Microangiopathies (MeSH: D057049); Microangiopathies, Thrombotic (MeSH: D057172); ADAMTS13 Protein (MeSH: C423082); Autoimmune Diseases (MeSH: D001327); Cardiovascular Diseases (MeSH: D002318); Epidemiologic Studies (MeSH: D004812); Retrospective Studies (MeSH: D012196); Observational Study (Publication Type); Risk Factors (MeSH: D012307); Treatment Outcome (MeSH: D016647); Rare Diseases (MeSH: D034381); Longitudinal Studies (MeSH: D008159); Patient Registry (MeSH: D010329); Survival (MeSH: D009505); Quality of Life (MeSH: D011788); Neurological Manifestations (MeSH: D009462)

Outcome Measures

Primary Outcomes (1)

• prevalence of major cardiovascular events

  ischemic strocke, myocardial infarction, reperfusion/angioplasty

  from diagnosis to last follow- up, up to 3 years

Secondary Outcomes (5)

• Incidence of cardiovascular risk factors

  from diagnosis to last follow- up, up to 3 years

• correlation between ADMTS13 activity during remission and incidence of cardiovascular events and life expectancy

  from remission to last follow- up, up to 3 years

• characterization of pregnancy onset iTTP

  from diagnosis to last follow- up, up to 3 years

• characterization of childhood onset iTTP

  from diagnosis to last follow- up, up to 3 years

• characterization of elderly onset iTTP

  from diagnosis to last follow- up, up to 3 years

Study Arms (1)

iTTP patients

The study is structured around one main cohort of all patients with immune thrombotic thrombocytopenic purpura (iTTP). Subgroup analyses are planned for specific populations: pregnant and postpartum women, pediatric patients, and elderly patients. There are no separate intervention or control groups; the design is a single retrospective cohort with multiple subgroup analyses.

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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.

You may qualify if:

• Patients with a diagnosis of immune mediated TTP

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Service d'Hématologie Hôpital Saint-Antoine

Paris, 75012, France

RECRUITING

MeSH Terms

Conditions

Purpura, Thrombotic Thrombocytopenic; Thrombotic Microangiopathies; Cardiovascular Diseases; Autoimmune Diseases; Rare Diseases; Neurologic Manifestations

Condition Hierarchy (Ancestors)

Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Thrombophilia; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms; Immune System Diseases; Disease Attributes; Nervous System Diseases

Study Officials

• Paul COPPO, MD, PHD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Paul COPPO, MD, PHD

CONTACT

00 33 1 49 28 34 39; aul.coppo@aphp.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 25, 2025
• First Posted: October 3, 2025
• Study Start: December 2, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: October 3, 2025

Record last verified: 2025-08

Locations

FR (1)