Optimizing ADAMTS13 prophylaxis to reduce relapse and organ failure in congenital thrombotic thrombocytopenic purpura.

Congenital thrombotic thrombocytopenic purpura (cTTP) is caused by a severe inherited ADAMTS13 deficiency. While acute episodes are life-threatening, long-term burden of ischemic complications and effectiveness of prophylactic strategies remain underexplored. We conducted a 25-year national, multicenter study of 88 cTTP patients enrolled in the French Thrombotic Microangiopathy (TMA) registry.

Trp1250, Lys1252 and Arg1367 of ADAMTS13 comprise a hot-spot for anti-CUB domain antibodies in patients with iTTP.

Immune mediated thrombotic thrombocytopenic purpura (iTTP) is a rare life-threatening thrombotic disorder, which results from the development of autoantibodies targeting ADAMTS13. The majority of patients (>90%) with iTTP display antibodies against a shared epitope in the spacer domain of ADAMTS13. Nevertheless, a smaller population of patients (20-40%) also has antibodies directed towards the CUB-domains of ADAMTS13.

Immune-mediated thrombotic thrombocytopenic purpura with systemic lupus erythematosus: clinical features and outcome.

Objective: The association of immune-mediated thrombotic thrombocytopenic purpura (iTTP) and SLE was previously described, but patients with iTTP with coexistent SLE remain poorly characterised.

Methods: We compared the clinical presentation and the outcome of patients with iTTP with coexistent SLE (SLE-iTTP) to an age-sex matched cohort of patients with idiopathic iTTP without SLE.

Results: During the study period, 1409 patients with iTTP were recruited in our registry.

Anti-ADAMTS13 Antibodies Trajectory is Associated With ADAMTS13 Recovery in Immune-Mediated TTP.

Current triplet regimens associating therapeutic plasma exchange (TPE), immunosuppression with corticosteroids and rituximab, and caplacizumab have dramatically improved the outcome of immune-mediated thrombotic thrombocytopenic purpura (iTTP). However, nearly half of the patients require extended caplacizumab treatment (i.e.

Diagnostic Value of Biological Parameters in Biopsy-Confirmed Thrombotic Microangiopathy-MATRIX Consortium Group.

Introduction: The diagnosis of thrombotic microangiopathy (TMA) relies on common biological parameters, the diagnostic value of which are unknown.

Methods: The presence of common biological parameters was assessed in 967 patients with TMA from 2009 to 2023 (ClinicalTrials.gov: NCT05991245).

Thrombotic thrombocytopenic purpura: early diagnosis and effective treatment in 2025.

In 2024, the centenary of thrombotic thrombocytopenic purpura (TTP) marks a significant milestone in the understanding and management of this rare and life-threatening condition. To commemorate this occasion, the European Society of Intensive Care Medicine launched an educational initiative aimed at consolidating and disseminating key knowledge on TTP, spanning its history, pathophysiology, diagnosis, and treatment. This paper summarizes the advances that have transformed TTP from a nearly universally fatal disease to one with a survival rate exceeding 95%.

2025 focused update of the 2020 ISTH guidelines for management of thrombotic thrombocytopenic purpura.

Background: Over the past few years, new information has emerged in the management of both immune thrombotic thrombocytopenic purpura (iTTP) and congenital (or hereditary) thrombotic thrombocytopenic purpura (cTTP).

Methods: In March 2024, the International Society on Thrombosis and Haemostasis (ISTH) formed a multidisciplinary panel comprising hematologists, intensivists, nephrologists, pathologists, patient representatives, and a methodology team. The panel discussed all treatment questions related to thrombotic thrombocytopenic purpura (TTP) using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method to appraise evidence and formulate recommendations.

How we manage immune-mediated thrombotic thrombocytopenic purpura after rituximab failure or intolerance.

The use of rituximab, a B-cell-depleting agent as a pre-emptive treatment in immune-mediated thrombotic thrombocytopenic purpura (iTTP), is the current standard of care. However, for patients refractory to rituximab or for those with contraindications, further treatment guidelines are scarce. Standard immunosuppressive or chemotherapeutic agents were used routinely in the past, but most of the data proving their efficacy are stemming from experience before the routine use of rituximab.

Caplacizumab use in immune-mediated thrombotic thrombocytopenic purpura: an international multicentre retrospective Cohort study (The Capla 1000+ project).

Background: The anti-Von Willebrand Factor (VWF) nanobody caplacizumab is licensed for adults with immune-mediated thrombotic thrombocytopenic purpura (iTTP) in association with therapeutic plasma exchange (TPE) and immunosuppression. However, whether caplacizumab reduces mortality, and its optimal timing of initiation, is not completely settled.

Methods: This international, multicenter retrospective cohort study recruited patients from 2018 until 2023 and data collection took place from January 1st to June 30th 2023 in the participating centers.

Pilot Study of Diagnostic Performances of Vascular Biomarkers Soluble fms-Like Tyrosine Kinase and Placental Growth Factor in Scleroderma Renal Crisis.

Introduction: Scleroderma renal crisis (SRC) is a major vascular complication of systemic sclerosis (SSc), associated with high morbidity and mortality. In this retrospective study, we evaluated the potential prognostic and diagnostic roles of angiogenesis molecules, placental growth factor (PlGF), soluble fms-like tyrosine kinase 1 (sFlt-1) and sFlt1/PlGF ratio as biomarkers in SRC.

Methods: Sera samples from 27 patients with a history of SRC (SSc-SRC+) were collected following event occurence.

A Thrombocytopenic Thrombotic Purpura in a Patient With a Metastatic HER2+ Breast Cancer: Description of a Case Report.

Paraneoplastic (p) TTP is a rare syndrome characterized by an immune-induced, generalized microangiopathy associated with solid or hematological tumors. This case, reporting a patient with a metastatic HER2+ breast cancer and a pTTP, highlights the rarity of this entity, its difficult and challenging diagnosis, and the complexity of its management.

Real-world evaluation of a novel automated method for measuring ADAMTS-13 activity using the Ceveron s100 analyzer.

Background: Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy characterized by a severe functional deficiency of ADAMTS-13. Measuring ADAMTS-13 activity is crucial for diagnosing TTP (<10 IU/dL), monitoring treatments, and detecting relapses (<20 IU/dL). The Technofluor assay (Technoclone) allows a rapid ADAMTS-13 activity measurement using the Ceveron s100 analyzer (Technoclone).

Thrombotic Thrombocytopenic Purpura: A Missed Cause in Stroke Prevention Guidelines.

The 2024 Guidelines for the Primary Prevention of Stroke, recently updated by the American Heart Association and the American Stroke Association, serve as an essential resource for clinicians aiming to reduce the growing impact of cerebrovascular disease. These guidelines emphasize modifiable risk factors and population-specific considerations, covering a range of cardiovascular conditions, including hypertension, diabetes, atherosclerotic disease, and genetic predispositions to stroke. However, a notable omission in these guidelines is the absence of specific recommendations for patients with thrombotic thrombocytopenic purpura.

N-glycan shielded CUB domains of ADAMTS13 prevent binding of C-terminal antibodies in patients with immune-mediated TTP.

In immune-mediated thrombotic thrombocytopenic purpura (iTTP), patients develop antibodies against ADAMTS13. Most patients exhibit inhibitory antispacer antibodies. Noninhibitory antibodies binding to the carboxy-terminal CUB domains have been suggested to enhance the clearance of ADAMTS13 in iTTP.

Incidence and impact of other malignancies after immunochemotherapy by fludarabine, cyclophosphamide, and rituximab as frontline treatment for chronic lymphocytic leukemia: A single-center retrospective study.

Individuals with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) have a high risk of developing other malignancies (OMs). The development of OMs may be associated with the advanced age of CLL/SLL patients, presence of a tumor-promoting microenvironment, immune alterations inherent to CLL/SLL, or chemotherapy. Importantly, the occurrence of OMs following frontline fludarabine, cyclophosphamide and rituximab (FCR) treatment is associated with a reduction in the overall survival (OS).

Acquired thrombotic thrombocytopenic purpura of unidentified pathophysiology in patients with severe disease: completing the landscape of thrombotic thrombocytopenic purpura.

Not available.

[Management of congenital thrombotic thrombocytopenic purpura in the era of recombinant ADAMTS13 protein: Recommendations from the Reference Center for Thrombotic Microangiopathies (CNR-MAT)].

Thrombotic Thrombocytopenic Purpura (TTP) is a rare disease characterized by a severe deficiency of ADAMTS13, the specific protease that cleaves von Willebrand factor. The congenital form of TTP (cTTP) results from pathogenic variants of the ADAMTS13 gene. cTTP has two peaks of incidence: one in childhood and the other in adulthood, mainly in an obstetric context.

Efficacy and safety of daratumumab in multiresistant immune-mediated thrombotic thrombocytopenic purpura.

The immunosuppressive treatment of immune-mediated thrombotic thrombocytopenic purpura (iTTP) in patients with intolerance or refractoriness to the B-cell depleting monoclonal antibody rituximab remains debated. Daratumumab, a plasma cell-directed monoclonal antibody targeting CD38, represents a therapeutic option, but data are scarce. The French Thrombotic Microangiopathies Reference Center conducted a nationwide survey on iTTP patients treated with daratumumab.

Clinical, biological, prognostic characteristics of patients with immune-mediated thrombotic thrombocytopenic purpura and Sjögren's disease.

Objectives: The association between immune-mediated thrombotic thrombocytopenic purpura (iTTP) and Sjögren disease (SjD) has been poorly investigated. This study presents the first retrospective cohort of iTTP-SjD aiming to identify risk factors for iTTP occurrence in SjD patients and examine their clinical course.

Methods: Patients with iTTP-SjD were identified within the French TTP Registry based on American College of Rheumatology/European League Against Rheumatism 2016 criteria.