...James N. George; J. Evan Sadler; Bernhard Lämmle Abnormalities of plasma von Willebrand factor (VWF) have been recognized to be associated with thrombotic thrombocytopenic purpura (TTP) for over 20 years. Patients with chronic, relapsing TTP have VWF multimers that are larger than normal, similar...

...Guomin Shen; Hao Zhang; Weidong Cui; Evan Sadler; Michael Gross; Weikai Li, PhD Warfarin targets vitamin K epoxide reductase (VKOR) to interfere with blood coagulation in humans. Warfarin is the most widely used oral anticoagulant, but its inhibition mechanism remains largely unknown. Here we use...

...J. Evan Sadler Copyright © 2007 by The American Society of Hematology 2007 References 1 Sadler JE, Budde U, Eikenboom JC, et al. Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor. J Thromb Haemost 2006...

...Kyuhwan Shim; Patricia J. Anderson; Elodee A. Tuley; Erin Wiswall; J. Evan Sadler Endothelial cells secrete prothrombotic ultralarge von Willebrand factor (VWF) multimers, and the metalloprotease ADAMTS13 cleaves them into smaller, less dangerous multimers. This reaction is stimulated by tensile...

...Evan Sadler The mechanism of idiopathic TTP appears to affect platelet thrombus formation by altering VWF-platelet dynamics, and the microvascular lesions contain platelets and VWF but scant fibrin. The possible involvement of factor V Leiden suggests that other mechanisms of TTP may depend...

...J. Evan Sadler Copyright © 2003 by The American Society of Hematology 2003 The recent characterization of a von Wille-brand factor cleaving protease, now called ADAMTS13, was a major breakthrough in understanding the pathogenesis of thrombotic thrombocytopenic purpura (TTP). Congenital...

...Jing Huang, PhD; Rodger P. McEver, Ph.D; John Heuser, Ph.D; J. Evan Sadler, MD/Ph.D Von Willebrand factor multimers that are tethered on endothelial cells are ultra large, hyperactive and susceptible to ADAMTS13 cleavage. However, the morphology of acutely secreted ULVWF that are deposited...

...Evan Sadler Wu and colleagues (page 3623 ) now have shown that a monoclonal antibody to VWF domain A3 that inhibits VWF-collagen binding in vitro can prevent platelet-rich thrombi from forming in damaged femoral arteries in vivo. At higher doses, the antibody also prolongs the skin bleeding...

...J. Evan Sadler, MD, PhD Von Willebrand factor (VWF) plays a central role in hemostasis, and dysregulation of VWF can cause either bleeding or thrombosis. Endothelial cells assemble VWF multimers in two stages that occur in distinct intracellular compartments: proVWF subunits dimerize...

...J. Evan Sadler The protein C pathway performs a critical anticoagulant function by subverting the procoagulant effects of thrombin, and a paper by Taylor and colleagues (page 1685 ) suggests that an endothelial membrane cofactor besides thrombomodulin modulates this function in vivo...

...Jing Huang, PhD, MD; Lisa A Westfield, Ph.D; J. Evan Sadler, MD, PhD Abstract 3311 The hemostatic function of von Willebrand factor (VWF) depends on the formation of disulfide-linked multimers. We have previously shown that several evolutionarily conserved His residues within the VWF propeptide...

...András Gézsi; Gábor Balázsi; Krisztina Sallai; Adrienn Mohl; Eszter Nagy, PhD; Teréz Szabó, MD; J. Evan Sadler, MD, PhD; Imre Bodó, MD, PhD The pathogenesis of VWD Vicenza has remained elusive. VWD Vicenza is characterized by low plasma but normal platelet VWF concentration, the presence...

...D'Andra Parker, BSc (Hon); Subia Tasneem, PhD; Nola Fuller, MSc; J. Evan Sadler, MD, PhD; Philip G de Groot, PhD; Catherine PM Hayward, MD, PhD Abstract 1144 Introduction: Multimerin 1 (MMRN1) is a massive variably-sized homopolymeric protein that is stored in platelet and endothelial cell...

...Jing Huang, PhD; John E. Heuser, MD; Rodger P. McEver, MD; J. Evan Sadler, MD, PhD Von Willebrand factor (VWF) multimers attached to endothelial cells can provide a platform for thrombosis, especially when accompanied by ADAMTS13 deficiency. We characterized the structural features of ultralarge...

...Weiqiang Gao, MD, PhD; Patricia J. Anderson, Ph.D; Elaine M. Majerus, MD, Ph.D; Elodee A. Tuley; J. Evan Sadler, MD,Ph.D ADAMTS13 is a member of the A D isintergrin A nd M etalloprotease with T hrombo S pondin type I repeat family, and it cleaves the Tyr 1605 -Met 1606 bond in the von Willebrand...

...Elaine M. Majerus, MD, PhD; Patricia J. Anderson, PhD; J. Evan Sadler, MD, PhD VWF multimers are cleaved into smaller less thrombogenic fragments in plasma by ADAMTS13. Deficiency of ADAMTS13 activity leads to thombotic thrombocytopenic purpura (TTP), a disease characterized by thrombocytopenia...

...Zheyong Yu, PhD; J. Evan Sadler, MD, PhD The metalloprotease ADAMTS13 regulates the size of released von Willebrand factor (VWF) multimers by cleaving a peptide bond in the VWF A2 domain. Unlike the other ADAMTS family members, ADAMTS13 contains two C-terminal CUB domains, and mutations...

...Ren-Huai Huang, PhD; David Fremont, PhD; Elodee A Tuley; John L Diener, PhD; Robert G Schaub, PhD; J. Evan Sadler, MD, PhD ARC1779 is a modified 40-mer oligonucleotide aptamer that binds with high affinity to the VWF A1 domain and blocks VWF binding to platelet GPIb-alpha. When given intravenously...

...Jeffrey I. Zwicker; Joshua Muia; Leili Dolatshahi; Lisa A. Westfield; Patricia Nieters; Anita Rodrigues; Ayad Hamdan; Ana G. Antun; Ara Metjian; J. Evan Sadler 28 06 2019 © 2019 by The American Society of Hematology 2019 TO THE EDITOR: The introduction of plasmapheresis...

...Jing Huang, PhD, MD; Fang Liu; J. Evan Sadler, MD, PhD Abstract 2113 Shiga toxin (Stx) causes diarrhea-associated hemolytic uremic syndrome (D+HUS) by damaging renal microvascular endothelium. Stx is composed of an active (A) N-glycosidase subunit that is responsible for cytotoxicity, and 5 binding...