Journal ArticleDOI
von Willebrand Factor–Cleaving Protease in Thrombotic Thrombocytopenic Purpura and the Hemolytic–Uremic Syndrome
Miha Furlan,Rodolfo Robles,Miriam Galbusera,Giuseppe Remuzzi,Paul A. Kyrle,Brigitte Brenner,Manuela Krause,Inge Scharrer,Volker Aumann,Uwe Mittler,Max Solenthaler,Bernhard Lämmle +11 more
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TLDR
In this article, the authors investigated the prevalence of von Willebrand factor-cleaving protease deficiency in patients with familial and non-familial forms of thrombocytopenic purpura and hemolytic-uremic syndrome.Abstract:
Background Thrombotic thrombocytopenic purpura and the hemolytic–uremic syndrome are severe microvascular disorders of platelet clumping with similar signs and symptoms. Unusually large multimers of von Willebrand factor, capable of agglutinating circulating platelets under high shear stress, occur in the two conditions. We investigated the prevalence of von Willebrand factor–cleaving protease deficiency in patients with familial and nonfamilial forms of these disorders. Methods Plasma samples were obtained from 53 patients with thrombotic thrombocytopenic purpura or hemolytic–uremic syndrome. Von Willebrand factor–cleaving protease was assayed in diluted plasma samples with purified normal von Willebrand factor as the substrate. The extent of the degradation of von Willebrand factor was assessed by electrophoresis in sodium dodecyl sulfate–agarose gels and immunoblotting. To determine whether an inhibitor of von Willebrand factor–cleaving protease was present, we measured the protease activity in normal ...read more
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Disseminated Intravascular Coagulation
Marcel Levi,Ten Cate H +1 more
TL;DR: Bleeding may be the presenting symptom in a patient with disseminated intravascular coagulation, a factor that can complicate decisions about treatment, and the use and subsequent depletion of platelets and coagulating proteins resulting from the ongoing coagulations may induce severe bleeding.
Journal ArticleDOI
Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome
TL;DR: Management of HUS remains supportive; there are no specific therapies to ameliorate the course, and the best way to prevent HUS is to prevent primary infection with Shiga-toxin-producing bacteria.
Journal ArticleDOI
Antibodies to von willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura
Han-Mou Tsai,Eric Chun-Yet Lian +1 more
TL;DR: Inhibitory antibodies against von Willebrand factor-cleaving protease occur in patients with acute thrombotic throm bocytopenic purpura, suggesting that a deficiency of this protease is likely to have a critical role in the pathogenesis of platelet thromBosis in this disease.
Journal ArticleDOI
Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura
Gallia Levy,William C. Nichols,Eric C.-Y. Lian,Tatiana Foroud,Jeanette N. McClintick,Beth McGee,Angela Y. Yang,David R. Siemieniak,Kenneth R. Stark,Ralph A. Gruppo,Ravindra Sarode,Susan B. Shurin,Visalam Chandrasekaran,Sally P. Stabler,Hernan Sabio,Eric E. Bouhassira,Jefferson D. Upshaw,David Ginsburg,Han-Mou Tsai +18 more
TL;DR: In this article, the ADAMTS family of zinc metalloproteinase genes (ADAMTS13) was identified as the molecular mechanism responsible for TTP, and it was shown that the deficiency of ADADTS13 is the molecular mechanisms responsible for the development of TTP.
Journal ArticleDOI
New fundamentals in hemostasis
TL;DR: This review summarizes new concepts of activation of proteases that regulate coagulation and anticoagulation, to give rise to transient thrombin generation and fibrin clot formation and speculates on the (patho)physiological roles of intra- and extravascular receptors that operate in response to these proteases.
References
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Journal ArticleDOI
Unusually large plasma factor VIII:von Willebrand factor multimers in chronic relapsing thrombotic thrombocytopenic purpura.
Joel L. Moake,Christine K. Rudy,Joseph H. Troll,Mark J. Weinstein,Noreen M. Colannino,José Azocar,Richard H. Seder,Suchen L. Hong,Daniel Deykin +8 more
TL;DR: A platelet-agglutinating factor has been detected in the plasma of some patients during episodes ofThrombotic thrombocytopenic purpura (TTP) and Agglutination induced in vitro by this plasma fac...
Journal ArticleDOI
Partial purification and characterization of a protease from human plasma cleaving von Willebrand factor to fragments produced by in vivo proteolysis
TL;DR: The size, amino acid composition, and amino terminal sequence of the reduced fragments confirmed that the peptide bond 842Tyr-843Met had been cleaved, ie, the same bond that has been proposed to be cleaved in vivo.
Journal ArticleDOI
Improved survival in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Clinical experience in 108 patients.
TL;DR: Effective treatment with 91 percent survival is available for patients with TTP-HUS, and treatment with aspirin and dipyridamole was effective in those with a poor response to plasma exchange.
Journal ArticleDOI
Physiologic cleavage of von Willebrand factor by a plasma protease is dependent on its conformation and requires calcium ion
TL;DR: The model that endothelial secreted vWF is converted to multimers by a novel plasma metalloproteinase is supported, as an alteration in the conformation by shear stress can lead to enhanced proteolytic susceptibility.
Journal ArticleDOI
Involvement of large plasma von Willebrand factor (vWF) multimers and unusually large vWF forms derived from endothelial cells in shear stress-induced platelet aggregation.
TL;DR: In this article, a fluid shear stress of 180 dyn/cm2 was applied for 0.5 and 5 min to platelets in citrated plasma or blood in a cone and plate viscometer with minimal platelet surface interactions.
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Antibodies to von willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura
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Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura
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