Caplacizumab reduces the frequency of major thromboembolic events, exacerbations, and death in patients with acquired thrombotic thrombocytopenic purpura.

BACKGROUND Acquired thrombotic thrombocytopenic purpura (aTTP) is a life-threatening autoimmune thrombotic microangiopathy. In spite of treatment with plasma exchange and immunosuppression, patients remain at risk for thrombotic complications, exacerbations and death. In the Phase II TITAN study, treatment with caplacizumab, an anti-vWF Nanobody(®) , was shown to reduce the time to confirmed platelet count normalization and exacerbations during treatment. OBJECTIVE The clinical benefit of caplacizumab was further investigated in a post-hoc analysis of the incidence of major thromboembolic events and exacerbations during the study drug treatment period and TTP-related death during the study. METHODS The Standardized MedDRA Query (SMQ) for 'embolic and thrombotic events' was run to investigate the occurrence of major thromboembolic events and exacerbations in the safety population of the TITAN study, which consisted of 72 patients of whom 35 received caplacizumab and 37 received placebo. RESULTS Four events (1 pulmonary embolism and 3 aTTP exacerbations) were reported in 4 patients in the caplacizumab group, while 20 such events were reported in 14 patients in the placebo group (2 acute myocardial infarctions, 1 ischemic and 1 hemorrhagic stroke, 1 pulmonary embolism, 1 deep vein thrombosis, 1 venous thrombosis and 13 aTTP exacerbations). Two of the placebo-treated patients died from aTTP during the study. CONCLUSION In total, 11.4% of caplacizumab-treated patients versus 43.2% of placebo-treated patients experienced one or more major thromboembolic event, an exacerbation or died. This analysis shows the potential for caplacizumab to reduce the risk of major thromboembolic morbidities and mortality associated with aTTP. This article is protected by copyright. All rights reserved

Consensus on the standardization of terminology in thrombotic thrombocytopenic purpura and related thrombotic microangiopathies

Essentials An international collaboration provides a consensus for clinical definitions. This concerns thrombotic microangiopathies and thrombotic thrombocytopenic purpura (TTP). The consensus defines diagnosis, disease monitoring and response to treatment. Requirements for ADAMTS-13 are given. Summary: Background Thrombotic thrombocytopenic purpura (TTP) and hemolytic\ue2\u80\u93uremic syndrome (HUS) are two important acute conditions to diagnose. Thrombotic microangiopathy (TMA) is a broad pathophysiologic process that leads to microangiopathic hemolytic anemia and thrombocytopenia, and involves capillary and small-vessel platelet aggregates. The most common cause is disseminated intravascular coagulation, which may be differentiated by abnormal coagulation. Clinically, a number of conditions present with microangiopathic hemolytic anemia and thrombocytopenia, including cancer, infection, transplantation, drug use, autoimmune disease, and pre-eclampsia and hemolysis, elevated liver enzymes and low platelet count syndrome in pregnancy. Despite overlapping clinical presentations, TTP and HUS have distinct pathophysiologies and treatment pathways. Objectives To present a consensus document from an International Working Group on TTP and associated thrombotic microangiopathies (TMAs). Methods The International Working Group has proposed definitions and terminology based on published information and consensus-based recommendations. Conclusion The consensus aims to aid clinical decisions, but also future studies and trials, utilizing standardized definitions. It presents a classification of the causes of TMA, and criteria for clinical response, remission and relapse of congenital and immune-mediated TTP

An expert discussion on the atypical hemolytic uremic syndrome nomenclature—identifying a road map to precision: a report of a National Kidney Foundation Working Group

\ua9 2024 International Society of NephrologyThe term atypical hemolytic uremic syndrome has been in use since the mid-1970s. It was initially used to describe the familial or sporadic form of hemolytic uremic syndrome as opposed to the epidemic, typical form of the disease. Over time, the atypical hemolytic uremic syndrome term has evolved into being used to refer to anything that is not Shiga toxin–associated hemolytic uremic syndrome. The term describes a heterogeneous group of diseases of disparate causes, a circumstance that makes defining disease-specific natural history and/or targeted treatment approaches challenging. A working group of specialty-specific experts in the thrombotic microangiopathies was convened to review the validity of this broad term in an era of swiftly advancing science and targeted therapeutics. A Delphi approach was used to define and interrogate some of the key issues related to the atypical hemolytic uremic syndrome nomenclature

A machine learning approach to predict mortality due to immune-mediated thrombotic thrombocytopenic purpura

Background: Mortality due to immune-mediated thrombotic thrombocytopenic purpura (iTTP) remains significant. Predicting mortality risk may potentially help individualize treatment. The French Thrombotic Microangiopathy (TMA) Reference Score has not been externally validated in the United States. Recent advances in machine learning technology can help analyze large numbers of variables with complex interactions for the development of prediction models. Objectives: To validate the French TMA Reference Score in the United States Thrombotic Microangiopathy (USTMA) iTTP database and subsequently develop a novel mortality prediction tool, the USTMA TTP Mortality Index. Methods: We analyzed variables available at the time of initial presentation, including demographics, symptoms, and laboratory findings. We developed our model using gradient boosting machine, a machine learning ensemble method based on classification trees, implemented in the R package gbm. Results: In our cohort (n = 419), the French score predicted mortality with an area under the receiver operating characteristic curve of 0.63 (95% CI: 0.50-0.77), sensitivity of 0.35, and specificity of 0.84. Our gradient boosting machine model selected 8 variables to predict acute mortality with a cross-validated area under the receiver operating characteristic curve of 0.77 (95% CI: 0.71-0.82). The 2 cutoffs corresponded to sensitivities of 0.64 and 0.50 and specificities of 0.76 and 0.87, respectively. Conclusion: The USTMA Mortality Index was acceptable for predicting mortality due to acute iTTP in the USTMA registry, but not sensitive enough to rule out death. Identifying patients at high risk of iTTP-related mortality may help individualize care and ultimately improve iTTP survival outcomes. Further studies are needed to provide external validation. Our model is one of many recent examples where machine learning models may show promise in clinical prediction tools in healthcare

Consensus on the standardization of terminology in thrombotic thrombocytopenic purpura and related thrombotic microangiopathies.

BACKGROUND Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are two important acute conditions to diagnose. Thrombotic Microangiopathy is a broad pathophysiological process that leads to microangiopathic hemolytic anemia, thrombocytopenia and involves capillary and small vessel platelet aggregates. The most common cause being disseminated intravascular coagulation (DIC), which may be differentiated by abnormal coagulation. Clinically, a number of conditions present with microangiopathic hemolytic anemia and thrombocytopenia (MAHAT), including cancer, infection, transplantation, drugs, autoimmune disease and pre-eclampsia and HELLP (Hemolysis, Elevated Liver enzymes, Low Platelet count) syndrome in pregnancy. Despite overlapping clinical presentations, TTP and HUS have distinct pathophysiology and treatment pathways. OBJECTIVES Presented is a consensus document from an international working group on TTP and associated TMAs (thrombotic microangiopathies). METHODS The international working group has proposed definitions and terminology based on published information and consensus based recommendations. CONCLUSION The consensus aims to aid clinical decisions but also future studies and trials, utilizing standardized definitions. It presents classification of the causes of TMA, and criteria for clinical response, remission and relapse of congenital and immune mediated TTP. This article is protected by copyright. All rights reserved