38 results match your criteria adamts13 newly


Early ADAMTS13 testing associates with pre-eclampsia occurrence in antiphospholipid syndrome.

Thromb Res 2021 07 27;203:101-109. Epub 2021 Apr 27.

Department of Gynaecology and Obstetrics, First Moscow State Medical University (Sechenov University), Russian Federation; Department of Haematology, CHU Nîmes, Univ Montpellier, Nîmes, France; Faculty of Pharmaceutical and Biological Sciences, Montpellier University, Montpellier, France; UA 011 INSERM- Université de Montpellier, Institut Desbrest d'Epidémiologie et de Santé Publique, Montpellier, France. Electronic address:

Introduction: Women with obstetric antiphospholipid syndrome (oAPS) still develop placental diseases, mainly pre-eclampsia (PEcl), which diagnosis is associated with reduced ADAMTS13 levels. Testing ADAMTS13 in newly pregnant oAPS may provide evidence for risk stratification.

Materials And Methods: We retrospectively investigated the prognostic value of ADAMTS13 activity, antigen and antibodies on stored plasma samples obtained prior to beginning low-molecular weight heparin-low dose aspirin treatment in 513 oAPS women. Read More

View Article and Full-Text PDF

Incidence, diagnosis, and outcome of immune-mediated thrombotic thrombocytopenic purpura: A nationwide survey by the Spanish registry of thrombotic thrombocytopenic purpura.

J Clin Apher 2021 Mar 29. Epub 2021 Mar 29.

Hospital Universitari Sagrat Cor, Barcelona, Spain.

Background: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare disease characterized by the presence of anti-ADAMTS13 autoantibodies. Achieving accurate information on incidence and customary disease management is important to provide appropriate diagnostic and therapeutic resources. The aim of this study was to determine the incidence and outcomes of iTTP in Spain. Read More

View Article and Full-Text PDF

Hemolysis and von Willebrand factor degradation in mechanical shuttle shear flow tester.

J Artif Organs 2021 Jun 9;24(2):111-119. Epub 2021 Feb 9.

Department of Preclinical Evaluation, Pre-Clinical Research Center, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.

Chronic blood trauma caused by the shear stresses generated by mechanical circulatory support (MCS) systems is one of the major concerns to be considered during the development of ventricular assist devices. Large multimers with high-molecular-weight von Willebrand factor (VWF) are extended by the fluid forces in a shear flow and are cleaved by ADAMTS13. Since the mechanical revolving motions in artificial MCSs induce cleavage in large VWF multimers, nonsurgical bleeding associated with the MCS is likely to occur after mechanical hemodynamic support. Read More

View Article and Full-Text PDF

The HLA Variant rs6903608 Is Associated with Disease Onset and Relapse of Immune-Mediated Thrombotic Thrombocytopenic Purpura in Caucasians.

J Clin Med 2020 Oct 21;9(10). Epub 2020 Oct 21.

Departmental Simple Unit of Pediatric Rheumatology, AUSL-IRCSS Reggio Emilia, 42123 Reggio Emilia, Italy.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening thrombotic microangiopathy caused by severe ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin motifs 13) deficiency, recurring in 30-50% of patients. The common human leukocyte antigen (HLA) variant rs6903608 was found to be associated with prevalent iTTP, but whether this variant is associated with disease relapse is unknown. To estimate the impact of rs6903608 on iTTP onset and relapse, we performed a case-control and cohort study in 161 Italian patients with a first iTTP episode between 2002 and 2018, and in 456 Italian controls. Read More

View Article and Full-Text PDF
October 2020

Upshaw-Schulman syndrome-associated ADAMTS13 variants possess proteolytic activity at the surface of endothelial cells and in simulated circulation.

PLoS One 2020 4;15(5):e0232637. Epub 2020 May 4.

Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

ADAMTS13 regulates the hemostatic activity of von Willebrand factor (VWF). Determined by static assays, proteolytic activity <10IU/dL in patient plasma, in absence of ADAMTS13 autoantibodies, indicates Upshaw-Schulman syndrome (USS); the congenital form of Thrombotic Thrombocytopenic Purpura (TTP). We have recently functionally characterized sixteen USS-associated ADAMTS13 missense variants under static conditions. Read More

View Article and Full-Text PDF

Thrombotic microangiopathy and liver toxicity due to a combination therapy of leflunomide and methotrexate: a case report.

J Med Case Rep 2020 Feb 5;14(1):26. Epub 2020 Feb 5.

Department of Internal Medicine 2, Halle University Hospital, Martin-Luther University Halle-Wittenberg, Ernst-Grube-Strasse 40, 06120, Halle (Saale), Germany.

Background: Treatment of active rheumatoid arthritis may necessitate a methotrexate mono- or combination therapy. As in the present case, novel side effects may occur, when escalating therapy.

Case Presentation: A 63-year-old Caucasian female patient with rheumatoid arthritis on methotrexate for 8 years and on leflunomide for 6 years was admitted for weakness, edema, ascites, and petechiae of the lower legs. Read More

View Article and Full-Text PDF
February 2020

Incidence of acquired thrombotic thrombocytopenic purpura in Germany: a hospital level study.

Orphanet J Rare Dis 2019 11 15;14(1):260. Epub 2019 Nov 15.

AHEAD GmbH, Agency for Health Economic Assessment and Dissemination, Lörrach, Germany.

Background: Acquired thrombotic thrombocytopenic Purpura (aTTP) is a life-threatening ultra-orphan disease with a reported annual incidence between 1.5 and 6.0 cases per million in Europe and mainly affecting otherwise young and healthy adults aged 40 years on average. Read More

View Article and Full-Text PDF
November 2019

Autoimmune Thrombotic Thrombocytopenic Purpura: Two Rare Cases Associated with Juvenile Idiopathic Arthritis and Multiple Sclerosis.

Front Med (Lausanne) 2017 24;4:89. Epub 2017 Jul 24.

4th Department of Internal Medicine, Hippokration Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Secondary thrombotic microangiopathies are associated with several underlying conditions, with most of them being resolved after the treatment of background disease. Thrombotic thrombocytopenic purpura (TTP) is a rare microangiopathy presenting with anemia, thrombocytopenia, and neurological deficits, occurring most often in various autoimmune diseases due to inhibition of ADAMTS13 by autoantibodies, as well as in pregnant women with or without an autoimmune substrate. In this article, we report two newly diagnosed TTP cases, who have not been published so far. Read More

View Article and Full-Text PDF

Evaluating the impact of the ABO blood group on the clinical outcome of thrombotic thrombocytopenic purpura associated with severe ADAMTS13 deficiency.

Authors:
E Hussein J Teruya

Vox Sang 2017 Jul 31;112(5):434-442. Epub 2017 Mar 31.

Pathology & Immunology, Pediatrics, and Medicine, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, USA.

Background And Objectives: Thrombotic thrombocytopenic purpura (TTP) is caused by the decrease of ADAMTS13, leading to the accumulation of ultra large von Willebrand factor (ULVWF). It was proposed that the distribution of blood group O among TTP patients may be potentially lower than expected because of the lower levels of VWF. The aim of this study was to explore the relationship between various blood groups and the clinical outcome in TTP. Read More

View Article and Full-Text PDF

[Changes of ADAMTS13 Activity and TSP1 Level in Patients with Hematologic Malignancies].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2016 Oct;24(5):1294-1298

Department of Hematology, The Central Hospital of Shengli Oilfield, Dongying 257000, Shandong Province, China. E-mail:

Objective: To investigate the changes of thrombospondin 1(TSP1) level and von Willebrand factor cleaving protease(ADAMTS13) activity in the patients with hematologic malignancies before and after treatment and to evaluate their clinical significance.

Methods: Eighty-two patients with hematologic malignancies were enrolled in this study, among them 20 patients were with acute leukemia, 48 patients were with lymphoma and 14 patients were with multiple myeloma. The plasma samples of 82 patients with hematologic malignancies and 45 healthy controls were collected. Read More

View Article and Full-Text PDF
October 2016

Generation of Anti-Murine ADAMTS13 Antibodies and Their Application in a Mouse Model for Acquired Thrombotic Thrombocytopenic Purpura.

PLoS One 2016 1;11(8):e0160388. Epub 2016 Aug 1.

Laboratory for Thrombosis Research, IRF Life Sciences, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium.

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening thrombotic microangiopathy linked to a deficiency in the metalloprotease ADAMTS13. In the current study, a novel mouse model for acquired TTP was generated to facilitate development and validation of new therapies for this disease. Therefore, a large panel (n = 19) of novel anti-mouse ADAMTS13 (mADAMTS13) monoclonal antibodies (mAbs) of mouse origin was generated. Read More

View Article and Full-Text PDF

Efficacy and safety of rituximab in Japanese patients with acquired thrombotic thrombocytopenic purpura refractory to conventional therapy.

Int J Hematol 2016 Aug 17;104(2):228-35. Epub 2016 May 17.

Division of Hematology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.

Thrombotic thrombocytopenic purpura (TTP), while rare, is a potentially life-threatening disorder. Plasma exchange (PE) is considered the primary treatment for TTP. In Western countries, rituximab, an anti-CD20 antibody, is recommended with PE for the treatment of refractory/relapsed TTP, and as up-front therapy in newly diagnosed TTP with neurological/cardiac pathology. Read More

View Article and Full-Text PDF

Clinical and prognostic significance of serum levels of von Willebrand factor and ADAMTS-13 antigens in AL amyloidosis.

Blood 2016 07 10;128(3):405-9. Epub 2016 May 10.

Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine, Athens, Greece;

Cardiac dysfunction determines prognosis in amyloid light-chain (AL) amyloidosis. The heart is the central organ of the vascular system in which endothelium function is critical for the circulatory homeostasis, but there are limited data on endothelial function in AL amyloidosis. von Willebrand factor (VWF) has been considered as a marker of endothelial activation and dysfunction, whereas a disintegrin and metalloproteinase with thrombospondin type-1 repeats 13 (ADAMTS-13) cleaves VWF multimers, but both have been associated with prognosis in cardiovascular disease. Read More

View Article and Full-Text PDF

Serial ADAMTS13 measurements during initial plasma exchange therapy guide decisions for management of unresponsive thrombotic thrombocytopenic purpura.

Transfusion 2015 Oct 26;55(10):2511-5. Epub 2015 Aug 26.

Department of Internal Medicine, Medical Center Leeuwarden, Leeuwarden, the Netherlands.

Background: The standard therapy in acquired thrombotic thrombocytopenic purpura (TTP) is plasma exchange. In unresponsive TTP, intensification of plasma exchange and immunomodulatory therapy can be initiated but it can be complicated to select for patients that will benefit from intensification.

Case Report: We describe two cases of newly diagnosed TTP with a complicated clinical course during initial treatment with plasma exchange. Read More

View Article and Full-Text PDF
October 2015

[Changes of ADAMTS13 activity and vWF antigen level in patients with acute myelogenous leukemia and their significance].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2014 Dec;22(6):1503-7

Department of Hematology, The First Affiliated Hospital of Suzhou University, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou 215006, Jiangsu Province, China.

This study was purposed to investigate the changes of von Willebrand factor cleaving protease (ADAMTS13) activity and vWF antigen level in patients with acute myelogenous leukemia (AML) before and after treatment and evaluate their clinical significance. Seventy-three AML patients were enrolled in this study, the sodium citrate anticoagulated plasma was collected before and after their induction chemotherapy. Fluorescence resonance energy transfer substrate vWF73 (FRETS-vWF73) assay was established to detect the plasma ADAMTS13 activity while vWF antigen level was measured by ELISA. Read More

View Article and Full-Text PDF
December 2014

Safety and efficacy of cryoprecipitate-poor plasma as a replacement fluid for therapeutic plasma exchange in thrombotic thrombocytopenic purpura: a single center retrospective evaluation.

J Clin Apher 2014 Dec 3;29(6):311-5. Epub 2014 Jun 3.

Hematology and Hemotherapy Center, University of Campinas, Campinas, São Paulo, Brazil.

Introduction: Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy caused by decreased activity of ADAMTS13, resulting in reduced clearance of ultralarge von Willebrand factor (VWF) multimers. Treatment of TTP is therapeutic plasma exchange (TPE) with replacement with fresh frozen plasma (FFP). Cryoprecipitate-poor plasma (CPP) is a plasma product with lower concentrations of large VWF multimers, and similar amounts of ADAMTS13. Read More

View Article and Full-Text PDF
December 2014

Acquired thrombotic thrombocytopenic purpura due to antibody-mediated ADAMTS13 deficiency precipitated by a localized Castleman's disease: a case report.

Platelets 2015 22;26(3):263-6. Epub 2014 May 22.

Hematology and Hemotherapy Center, University of Campinas, Hemocentro-Unicamp, Instituto Nacional de Ciência e Tecnologia do Sangue , Campinas , Brazil .

Acquired ADAMTS13 inhibitor causing thrombotic thrombocytopenic purpura (TTP) may be precipitated by some infections, inflammatory diseases or neoplasia. We reported a case of refractory TTP precipitated by a newly diagnosed localized Castleman's disease (CD). TTP was initially treated with plasma exchange and immunosuppressive therapy with corticosteroids; however the treatment failed to promote sustained response. Read More

View Article and Full-Text PDF
December 2015

Plasma pentraxin-3 and coagulation and fibrinolysis variables during acute Puumala hantavirus infection and associated thrombocytopenia.

Blood Coagul Fibrinolysis 2014 Sep;25(6):612-7

aDepartment of Internal Medicine, Tampere University Hospital bSchool of Medicine, University of Tampere cCoagulation Disorders, Department of Clinical Chemistry (HUSLAB Laboratory Services), Helsinki University Central Hospital dSchool of Health Sciences, University of Tampere eDepartment of Virology, Haartman Institute, University of Helsinki fLaboratory Centre, Tampere University Hospital, Tampere, Finland.

Thrombocytopenia and altered coagulation characterize all hantavirus infections. To further assess the newly discovered predictive biomarkers of disease severity during acute Puumala virus (PUUV) infection, we studied the associations between them and the variables reflecting coagulation, fibrinolysis and endothelial activation. Nineteen hospital-treated patients with serologically confirmed acute PUUV infection were included. Read More

View Article and Full-Text PDF
September 2014

A new mouse model mimicking thrombotic thrombocytopenic purpura: correction of symptoms by recombinant human ADAMTS13.

Blood 2012 Jun 23;119(25):6128-35. Epub 2012 Apr 23.

Department of Preclinical Pharmacology & Toxicology, Baxter Innovations GmbH, Industriestrasse 67, Vienna, Austria.

Deficiency of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13), a VWF-cleaving protease, is the key factor in the pathogenesis of thrombotic thrombocytopenic purpura (TTP), a life-threatening thrombotic microangiopathy. It is well established that ADAMTS13 deficiency results in elevated plasma levels of ultra-large VWF multimers (ULVWF), which are prone to induce platelet aggregation; however, the actual trigger of TTP development remains uncertain. Here we describe a new animal model in which some TTP-like symptoms can be triggered in ADAMTS13 knockout mice by challenge with 2000 units/kg body weight of recombinant human VWF containing ULVWF multimers. Read More

View Article and Full-Text PDF

Thrombotic microangiopathy due to multiple autoantibodies related to antiphospholipid syndrome.

Pediatr Nephrol 2012 Apr 31;27(4):681-5. Epub 2011 Dec 31.

Division of Nephrology and Rheumatology, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan.

Background: Antiphospholipid syndrome (APS) is a rare disorder in children. More than half of childhood APS occurs as secondary APS complicated by systemic lupus erythematosus (SLE) and other autoimmune diseases.

Case-diagnosis/treatment: We encountered a boy with SLE who presented with thrombotic microangiopathy (TMA) due to APS. Read More

View Article and Full-Text PDF

Shear stress-induced unfolding of VWF accelerates oxidation of key methionine residues in the A1A2A3 region.

Blood 2011 Nov 13;118(19):5283-91. Epub 2011 Sep 13.

Research Division, Puget Sound Blood Center, Seattle, WA 98104, USA.

VWF is required for platelet adhesion to sites of vessel injury, a process vital for both hemostasis and thrombosis. Enhanced VWF secretion and oxidative stress are both hallmarks of inflammation. We recently showed that the neutrophil oxidant hypochlorous acid (HOCl) inhibits VWF proteolysis by ADAMTS13 by oxidizing VWF methionine 1606 (M1606) in the A2 domain. Read More

View Article and Full-Text PDF
November 2011

Predictive features of severe acquired ADAMTS13 deficiency in idiopathic thrombotic microangiopathies: the French TMA reference center experience.

PLoS One 2010 Apr 23;5(4):e10208. Epub 2010 Apr 23.

Service d'Hématologie et de Thérapie Cellulaire, AP-HP, Hôpital Saint-Antoine, Paris, France.

Severe ADAMTS13 deficiency occurs in 13% to 75% of thrombotic microangiopathies (TMA). In this context, the early identification of a severe, antibody-mediated, ADAMTS13 deficiency may allow to start targeted therapies such as B-lymphocytes-depleting monoclonal antibodies. To date, assays exploring ADAMTS13 activity require skill and are limited to only some specialized reference laboratories, given the very low incidence of the disease. Read More

View Article and Full-Text PDF

Von Willebrand factor, ADAMTS-13, and thrombotic thrombocytopenic purpura.

Semin Thromb Hemost 2010 Feb 13;36(1):71-81. Epub 2010 Apr 13.

Department of Medicine, Baylor College of Medicine, Houston, TX, USA.

For a disease with <80 years of history, clinical and basic research into thrombotic thrombocytopenic purpura (TTP) has been significantly accelerated since the identification of unusually large von Willebrand factor (VWF) multimers and deficiency of ADAMTS-13 ( A Disintegrin And Metalloproteinase with Thrombo Spondin-1-like domains) as the potential cause. The VWF-cleaving metalloprotease ADAMTS-13 has since been extensively characterized and its biological action tested in vitro and in vivo. There have also been considerable efforts to understand the interaction between ADAMTS-13 and its substrate VWF, as well as its biological regulation. Read More

View Article and Full-Text PDF
February 2010

[New marker in thrombotic thrombocytopenic purpura].

Ugeskr Laeger 2008 Aug;170(33):2446-9

Rigshospitalet, Klinisk Biokemisk Afdeling, Københavns Universitet, Biomedicinsk Institut, København Ø.

Thrombotic microangiopathy can be caused by several conditions which are difficult to diagnose from the clinical presentation alone. Deficient enzyme activity of a newly-discovered enzyme, ADAMTS-13, can lead to thrombotic thrombocytopenic purpura (TTP). Lack of ADAMTS-13 activity causes increased concentrations of high molecular weight von Willebrand factor forms and increased platelet aggregation. Read More

View Article and Full-Text PDF

Magnesium maintains endothelial integrity, up-regulates proteolysis of ultra-large von Willebrand factor, and reduces platelet aggregation under flow conditions.

Thromb Haemost 2008 Mar;99(3):586-93

Section of Thrombosis Research, Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.

Mg (++) regulates endothelial functions and has anti-inflammatory effects. Its effects on thrombosis have been demonstrated, but the mechanism remains poorly understood. We investigated the roles of MgSO(4) in regulating the release and cleavage of the prothrombotic ultra-large (UL) von Willebrand factor (VWF) and VWF-mediated platelet adhesion and aggregation. Read More

View Article and Full-Text PDF

von Willebrand factor, von Willebrand factor-cleaving protease, and shear stress.

Cardiovasc Hematol Agents Med Chem 2007 Oct;5(4):305-10

Hemostasis and Thrombosis Unit, Department of Hematology and Oncology, Giannia Gaslini Children's Hospital, Largo G. Gaslini, 5, I-16147 Genova, Italy.

von Willebrand factor (VWF) is a multimeric plasma glycoprotein (GP) involved in platelet adhesion at the site of vascular damage, which acts as a bridge between the injured subendothelium and the platelet receptors. The multimeric structure of VWF allows it to support multiple interactions with platelets and endothelial components under high shear stress. Rapid flow conditions induce a conformational transition of the VWF molecule, thus allowing its functional binding domains to be exposed. Read More

View Article and Full-Text PDF
October 2007

[Development of a novel ADAMTS13 activity assay for diagnosis of TMA and criteria for judgment of platelet transfusion].

Authors:
Hisahide Hiura

Rinsho Byori 2007 Jan;55(1):69-75

Japan Clinical Laboratories, Inc. Kyoto.

ADAMTS13 specifically cleaves unusually large von Willebrand factor (VWF) multimers, which induce platelet thrombi formation under high shear stress. The determination of plasma levels of ADAMTS13 activity is prerequisite for a differential diagnosis of thrombotic microangiopathies (TMAs). Here, we describe a unique and highly sensitive enzyme immunoassay of ADAMTS13 activity for routine laboratory use. Read More

View Article and Full-Text PDF
January 2007

Acute activation of the endothelium results in increased levels of active von Willebrand factor in hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome.

J Thromb Haemost 2006 Dec 12;4(12):2569-75. Epub 2006 Sep 12.

Department of Haematology, University Medical Centre Utrecht, Utrecht, the Netherlands.

Background: HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome is a severe complication of pre-eclampsia in pregnancy, characterized by microvascular platelet thrombi. Activation of the endothelium is thought to play a key role in pre-eclampsia and HELLP syndrome. Activation of endothelial cells may lead to release of von Willebrand factor (VWF) multimers, which are highly reactive with platelets. Read More

View Article and Full-Text PDF
December 2006

[A clinical study of congenital thrombotic thrombocytopenic purpura].

Zhonghua Nei Ke Za Zhi 2006 Jun;45(6):482-4

Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, Suzhou 215006, China.

Objective: To study on the first Chinese congenital thrombotic thrombocytopenic purpura (TTP) patient with respect to peripheral blood platelet count and ADAMTS13 activity, ADAMTS13 antigen, anti-endothelial cell antibody (ACEA), and thrombospondin1 (TSP1) etc. to compared it with idiopathic TTP and to explore something special and meaningful in the pathogenesis of congenital TTP.

Methods: A total of 30 volunteers served as controls. Read More

View Article and Full-Text PDF

[Determination of the ADAMTS13 antigen and its activity in TTP patients and carriers].

Zhonghua Xue Ye Xue Za Zhi 2006 Mar;27(3):154-7

Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou 215006, China.

Objective: To investigate the antigen levels and activity of von Willebrand factor cleaving protease ADAMTS13 in thrombotic thrombocytopenic purpura (TTP) patients and carriers.

Methods: 28 samples from 13 TTP patients and 10 samples from the carriers were examined. The activity of ADAMTS13 was measured by residue collagen binding assay, and antigen by a newly developed sandwich ELISA. Read More

View Article and Full-Text PDF