ADAMTS-13

Congenital thrombotic thrombocytopenic purpura (TTP) is a rare autosomal recessive genetic disorder caused by mutations in the ADAMTS13 gene. Approximately 200 mutations of the ADAMTS-13 gene have been identified, although only a few have been characterized through in vitro expression studies. We conducted an investigation on a male congenital TTP patient with reduced plasma levels of ADAMTS13 activity. DNA sequence analysis revealed two mutations on chromosome 9 ( 1.9q34.2 ) in the patient's ADAMTS13 gene...

•Data on caplacizumab use for thrombotic thrombocytopenic purpura (TTP) in Italy are missing.•Twenty-six Italian patients were treated with caplacizumab for an acute immune TTP episode.•Caplacizumab was effective in treating acute TTP in the Italian real-world clinical setting.•Two major bleeds leading to drug discontinuation were observed.

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. Yet, FO-SPR has never been explored to measure enzymatic activities. OBJECTIVES: To develop an easy-to-use ADAMTS-13 activity assay utilizing optical fibers to rapidly diagnose TTP...

PURPOSE: Hepatitis E virus infection mainly presents with liver-related symptoms, and multiple studies have shown that hepatitis E virus infection can also induce extrahepatic-related symptoms. Thrombotic thrombocytopenic purpura is an uncommon and fatal thrombotic microangiopathy characterized by severe thrombocytopenia, organ damage, and microangiopathic haemolytic anaemia. We report the first case in which acute hepatitis E induced the first episode of immune-mediated thrombotic thrombocytopenic purpura...

BACKGROUND: von Willebrand factor (VWF) is a multimeric glycoprotein critically involved in hemostasis, thrombosis, and inflammation. VWF function is regulated by its antigen levels, multimeric structures, and the state of enzymatic cleavage. Population studies in the past have focused almost exclusively on VWF antigen levels in cross-sectional study designs. OBJECTIVE: To identify subjects in the Atherosclerosis Risk in Community study who had persistent low and high VWF antigen over 10 years and to quantify longitudinal changes in the biological activities and cleavage of VWF in these subjects...

When stimulated by proinflammatory mediators, endothelial cells release ultra-large von Willebrand factor (ULVWF) multimers that are hyperactive in activating and aggregating platelets. These ULVWF multimers can accumulate in the circulation and on the inflamed endothelium because they are insufficiently cleaved by the metalloprotease ADAMTS-13, which becomes moderately deficient under conditions of systemic inflammation. This moderate ADAMTS-13 deficiency may lead to thrombotic complications that contribute to ischemic tissue injury and organ failure that are associated with severe infections...

PURPOSE OF REVIEW: This review provides an update on recent advances in mechanistic studies of thromboinflammatory mechanisms that contribute to the disease pathology in sickle cell disease (SCD). There is a focus on novel pathways, clinical relevance, and translational potential of these findings. We hope to encourage more advances in this area to reduce organ damage in young patients prior to gene therapy, and to serve the aging SCD patient population. RECENT FINDINGS: Novel insights into the roles of neutrophils, the ADAMTS-13/VWF axis, oxidative stress, and the intrinsic coagulation cascade, as well as relevant clinical trials, are discussed...

Fibrosis is an unavoidable consequence of chronic inflammation. Extracellular matrix deposition by fibroblasts, stimulated by multiple pathways, is the first step in the onset of chronic liver disease, and its propagation promotes liver dysfunction. At the same time, chronic liver disease is characterized by alterations in primary and secondary hemostasis but unlike previously thought, these changes are not associated with an increased risk of bleeding complications. In recent years, the role of coagulation imbalance has been postulated as one of the main mechanisms promoting hepatic fibrogenesis...

INTRODUCTION: Alterations in the endothelium and endothelial adhesion proteins such as von Willebrand factor (vWF) play major roles in hypercoagulability in thalassemia. vWF protein release leads to platelet aggregation and thrombi formation at the site of vascular injury. It is then degraded by the proteolytic enzyme ADAMTS13. Thrombospondin-1 is a multifactorial glycoprotein, which was reported to compete with ADAMTS13 for sites of vWF proteolysis. In this study, levels of vWF, ADAMTS13, and TSP-1 proteins were determined in β-thalassemia major patients...

SUMMARY: Systemic thrombotic microangiopathy (TMA) is a serious condition whose early treatment is essential to reduce morbidity and mortality. TMA with only renal involvement has been associated with tyrosine kinase inhibitors, including lenvatinib, a drug used for certain advanced neoplasms. To date, TMA with systemic involvement associated with this drug has not been described. We present the case of a patient with progressive metastatic thyroid cancer who developed this complication after starting treatment with lenvatinib...

Thrombotic thrombocytopenic purpura (TTP) is a diffused microvascular occlusive disorder characterized by microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and ischemic organ dysfunction. In addition, this condition has been linked to an absence or dysfunction of ADAMTS13. Although TTP can occur due to various factors, such as bacteria, viruses, autoimmune disorders, drugs, connective tissue conditions, and solid tumors, it is a rare hematological complication associated with brucellosis. We describe the first case of a 9-year-old boy with acquired TTP with undetectable ADAMTS-13 assay secondary to Brucella infection...

In addition to kidney replacement procedures, several other extracorporeal procedures are employed in the intensive care unit. Hemoperfusion with activated charcoal was the predominant treatment used for removal of toxins from the 1970s until the millennium. Nowadays, this treatment does no longer play a clinically meaningful role as even strongly protein-bound toxins can be removed by effective dialysis procedures in case poisoning. The concept of a cytokine adsorber was introduced 10 years ago, which is directed towards withstanding the cytokine storm...

BACKGROUND: The covid-19 disease has caused many deaths worldwide since December 2019. Many thromboembolic events, such as VTE and TTP, have been reported since the beginning of this pandemic. Considering the prominent role of complement in developing TTP and TTP-like syndrome in recent studies, this study aimed to assess the prevalence of TTP-like syndrome and its relationship with complement activity in critically ill patients with COVID-19. METHOD: This study was conducted on 77 COVID-19 patients admitted to the ICU wards of Tabriz Imam Reza hospital from March to June 2021...

Thrombotic thrombocytopenic purpura (TTP), a rare and lethal thrombotic microangiopathy, is an autoimmune disease that can be triggered by viral infections such as COVID-19. This condition is characterized by hemolytic microangiopathy, thrombocytopenia, and neurologic alterations, possibly accompanied by fever and renal damage. Moreover, more than 220 patients with Guillain-Barré syndrome (GBS) have been reported in association with the COVID-19 infection. In this report, we present a case of a patient who developed refractory TTP complicated by GBS following a SARS-CoV-2 infection...

BACKGROUND: von Willebrand factor (VWF) multimers are cleaved by A disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13 (ADAMTS-13) into less active fragments. Thrombospondin 1 (TSP-1) competes with VWF's cleavage site, protecting it from degradation. Low ADAMTS-13 and high VWF have been associated with cardiovascular disease and atrial fibrillation (AF). OBJECTIVES: We aimed to investigate whether VWF, ADAMTS-13, and TSP-1 are associated with clinical outcome...

UNLABELLED: Sepsis-induced coagulopathy leading to disseminated microvascular thrombosis is associated with high mortality and has no existing therapy. Despite the high prevalence of Gram-positive bacterial sepsis, especially methicillin-resistant Staphylococcus aureus (MRSA), there is a paucity of published Gram-positive pediatric sepsis models. Large animal models replicating sepsis-induced coagulopathy are needed to test new therapeutics before human clinical trials. HYPOTHESIS: Our objective is to develop a pediatric sepsis-induced coagulopathy swine model that last 70 hours...

Vaccine-associated thrombotic thrombocytopenic purpura (TTP) is a rare type of acquired TTP recently reported after COVID-19 vaccination. Merely four cases are ascribed to the ChAdOx1 nCoV-19 vaccine in the medical literature till the preparation of this study. In this case report, we describe a 43-year-old man who developed symptoms of TTP four days after receiving the second dose of the ChAdOx1 nCoV-19 vaccine. Peripheral blood smear demonstrated multiple schistocytes. Given a high plasmic score, he received plasma exchange, corticosteroids, and rituximab, and later, low ADAMTS 13 activity and high-titer ADAMTS inhibition antibody confirmed the diagnosis of COVID-19 vaccine-associated TTP...

The coexistence of anti-glomerular basement membrane (anti-GBM) disease with thrombotic microangiopathy (TMA) is rarely encountered, and the clinical characteristics of this phenomenon are not well known.A 76-year-old Japanese woman with a history of idiopathic pulmonary disease was diagnosed with anti-GBM disease due to rapidly progressive glomerulonephritis and a positive anti-GBM antibody test result. We treated the patient with hemodialysis, glucocorticoids, and plasmapheresis. During treatment, the patient suddenly became comatose...

OBJECTIVE:  To investigate the appropriateness of Bentley and plasmic scores and ADAMTS-13 activity to distinguish between primary thrombotic microangiopathies (TMA) syndromes and other thrombotic microangiopathies, as well as primary thrombotic microangiopathies (TTP, complement-related TMA, etc). STUDY DESIGN:  Descriptive study. Place and Duration of the Study: Department of Hematology, Faculty of Medicine, from February 2013 to February 2020. METHODOLOGY: Data of patients with non-immune hemolytic anaemia (MAHA) and thrombocytopenia who had ADAMTS-13 test, were analysed...

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy caused by a hereditary or immune-mediated deficiency of the enzyme ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13). TTPs are caused by the following pathophysiological mechanisms: (1) the presence of inhibitory autoantibodies against ADAMTS13; and (2) hereditary mutations of the ADAMTS13 gene, which is present on chromosome 9. In both syndromes, TTP results from a severe deficiency of ADAMTS13, which is responsible for the impaired proteolytic processing of high-molecular-weight von Willebrand factor (HMW-VWF) multimers, which avidly interact with platelets and subendothelial collagen and promote tissue and multiorgan ischemia...