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. The majority of patients exhibit inhibitory anti-spacer antibodies. Non-inhibitory antibodies binding to the carboxy-terminal CUB domains have been suggested to enhance the clearance of ADAMTS13 in iTTP.

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.

Real-Life Management of Patients Aged 80 Years Old and Over With Multiple Myeloma: Results of the EMMY Cohort.

Introduction: Multiple myeloma patients aged 80 years and older are a population more prone to comorbidities and frailty. We aim to describe the real-life management and outcomes of this population. EMMY is a descriptive large-scale study.

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.

Using Digital Storytelling as an Evaluation Tool.

Digital storytelling is an innovative approach that evaluators can adopt to expand their dissemination efforts. The stories use brief audio and video recordings, and they can be used to provide reflections on the perceived value, experiences, or impact of public health efforts. We offer tips for evaluators to add this tool to their portfolio using several traditional evaluation data collection techniques.

Carfilzomib-associated thrombotic microangiopathy: clinical features and outcomes.

Background: Carfilzomib, a new proteasome inhibitor indicated for patients with relapsed/refractory myeloma, has been associated with cases of thrombotic microangiopathy (CFZ-TMA). The role of variants in the complement alternative pathway and therapeutic potential of complement blockade with eculizumab remain to be determined.

Methods: We report 37 cases of CFZ-TMA recorded in the French reference center for TMA with their clinical characteristics, genetic analysis and outcome according to treatments.

Diagnosis of thrombotic thrombocytopenic purpura: easy-to-use fiber optic surface plasmon resonance immunoassays for automated ADAMTS-13 antigen and conformation evaluation.

Background: Laboratory diagnosis of immune-mediated thrombotic thrombocytopenic purpura (iTTP) remains challenging when ADAMTS-13 activity ranges between 10% and 20%. To prevent misdiagnosis, open ADAMTS-13 conformation gained clinical attention as a novel biomarker, especially to diagnose acute iTTP in patients with diagnostic undecisive ADAMTS-13 activity. Plasma ADAMTS-13 conformation analysis corrects for ADAMTS-13 antigen, with both parameters being characterized in enzyme-linked immunosorbent assay (ELISA)-based reference assays requiring expert technicians.

Hemophagocytic lymphohistiocytosis is associated with deficiency and closed conformation of ADAMTS-13.

Background: A disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13 (ADAMTS-13) is the specific von Willebrand factor-cleaving protease and circulates in a closed and latent conformation due to a spacer/CUB1 domain interaction. ADAMTS-13 is allosterically activated after binding of its substrate or antibodies, inducing an open conformation. Recently, we suggested a potential role of plasmin (fibrinolysin) in hemostasis disorders reported in most patients with hemophagocytic lymphohistiocytosis (HLH), a rare and life-threatening condition related to a severe systemic inflammatory state.

Alemtuzumab-induced immune-mediated thrombotic thrombocytopenic purpura: A newly described drug-related autoimmune disease.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare and life-threatening disease that may result from drug exposure. We report a case of iTTP occurring in a 39-year-old patient, 45 months following introduction of the anti-CD52 lymphoid cell depleting monoclonal antibody alemtuzumab, to treat a relapsing-remitting multiple sclerosis. Treatment consisted in plasma exchange, corticosteroids and caplacizumab, allowing clinical remission 3 months after the diagnosis, attested by the absence of thrombocytopenia and recovery of ADAMTS-13 activity.

Management and follow-up of pregnancy-onset thrombotic thrombocytopenic purpura: the French experience.

Pregnancy-onset thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening disease of which diagnosis and management requires experienced multidisciplinary teams. The mechanisms responsible for a deficiency in the disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13 (ADAMTS13) leading to pregnancy-onset TTP may be congenital or acquired, and studying ADAMTS13 conformation could be of interest. The differential diagnosis between TTP and other pregnancy-associated thrombotic microangiopathies (TMA) is often challenging.

Bothrops venom-induced hemostasis disorders in the rat: Between Scylla and Charybdis.

Hemostasis impairment represents the most threatening consequence of Viperidae envenoming, notably with Bothrops genus. In the French departments of America, B. atrox envenomation in French Guiana may lead to bleeding while B.

Open ADAMTS-13 conformation index predicts earlier relapse in immune-mediated thrombotic thrombocytopenic purpura.

Background: ADAMTS-13 adopts an open conformation in patients with immune-mediated thrombotic thrombocytopenic purpura (iTTP) in acute phase while being closed in healthy donors. We reported that a substantial number of patients with iTTP in remission with restored ADAMTS-13 activity (>50%) still had an open ADAMTS-13 conformation, although a closed conformation is expected given the extent of remission.

Objectives: To investigate whether open ADAMTS-13, represented by a conformation index >0.

Return to military duty following anterior cruciate ligament reconstruction is associated with preoperative Body Mass Index and postoperative physiotherapy.

Purpose: To determine the rate and time of return to duty following anterior cruciate ligament reconstruction (ACLR) in military members, and to determine whether their outcomes are influenced by patient characteristics or surgical parameters.

Methods: We prospectively assessed 280 military members that underwent ACLR. 27 were excluded due to multi-ligamentous injuries or revision surgery, two did not provide informed consent and 62 were lost to follow-up.

Measuring ADAMTS-13 activity to diagnose thrombotic thrombocytopenic purpura: a novel, fast fiber-optic surface plasmon resonance immunoassay.

Background: Thrombotic thrombocytopenic purpura (TTP) is characterized by severe ADAMTS-13 activity deficiency (<10%). Diagnostic testing is challenging because of unavailability, high cost, and expert technician requirement of ADAMTS-13 enzyme assays. Cost-effective, automated fiber-optic surface plasmon resonance (FO-SPR) platforms show potential for developing diagnostic tests.

Impact of N-glycan mediated shielding of ADAMTS-13 on the binding of pathogenic antibodies in immune thrombotic thrombocytopenic purpura.

Background: Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic disorder, with 1.5 to 6.0 cases per million per year.

Caplacizumab: A game changer also in pregnancy-associated immune-mediated thrombotic thrombocytopenic purpura?

Therapeutic options in immune-mediated thrombotic thrombocytopenic purpura (iTTP) during pregnancy are limited besides therapeutic plasma exchange (TPE) and corticosteroids. The report by Odetola et al. suggests that caplacizumab represents a reasonable option in iTTP during pregnancy, especially when the disease is not rapidly controlled with the standard TPE-corticosteroid association.

The Specificities of Thrombotic Thrombocytopenic Purpura at Extreme Ages: A Narrative Review.

Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening thrombotic microangiopathy (TMA) related to a severe ADAMTS13 deficiency, the specific von Willebrand factor (VWF)-cleaving protease. This deficiency is often immune-mediated (iTTP) and related to the presence of anti-ADAMTS13 autoantibodies that enhance its clearance or inhibit its VWF processing activity. iTTP management may be challenging at extreme ages of life.