50th ASH Annual Meeting and Exposition (December 6 - 9, 2008): Blood Coagulation and Fibrinolytic Factors Poster III

Monday, December 8, 2008: 5:30 PM-7:30 PM

Hall A (Moscone Center)

Substitution of Four Residues Revealed by High-Throughput Screening of Human Factor VIII A2 Domain Generated a Recombinant Molecule That Escapes to Anti-Factor VIII Antibodies

Jean-Luc Plantier¹^*, Didier Saboulard²^*, Marc Delcourt²^*, Nathalie Enjolras¹^* and Claude Negrier, MD³

¹IFR62-Faculté de médecine RTH Laennec, Laboratoire d'hémobiologie-EA4174, Lyon, France
²Biomethodes, Evry, France
³Centre de Traitement, Lyon, France

3068

Inhibition of Pulmonary Coagulopathy by Nebulized Natural Anticoagulants during Streptococcus Pneumoniae Pneumonia in Rats

J. J. Hofstra, MD¹^*, F. E. van den Boogaard, MD²^*, A. D. Cornet, MD³^*, A. P.J. Vlaar, MD²^*, T. van der Poll, Prof, MD, PhD¹^*, M. Levi, Prof, MD, PhD¹^* and M. J. Schultz, MD, PhD⁴^*

¹Department of Internal Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, Netherlands
²Laboratory of Experimental Intensive Care and Anesthesiology, Academic Medical Centre, University of Amsterdam, Amsterdam, Netherlands
³Department of Intensive Care Medicine, VU Medical Center, Free University of Amsterdam, Amsterdam, Netherlands
⁴Department of Intensive Care Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam

3069

A FVIII C1 Domain Loop Containing Phe2093 Contributes Affinity to the Binding of Recombinant FVIII C1C2 Proteins to Activated Platelets

Ting-Chang Hsu, Ph.D.^*, Kathleen P. Pratt, Ph.D. and Arthur R. Thompson, M.D., Ph.D.

Puget Sound Blood Center, Seattle, WA

3070

Conformational Activation of Zymogen-Like Thrombin Variants by Tight Binding Ligands

Anuja Khan, PhD¹^*, Peter Panizzi, PhD²^*, Heather K Kroh, PhD²^*, Paul E. Bock, PhD²^* and Sriram Krishnaswamy, PhD¹

¹Children's Hospital of Philadelphia, Philadelphia, PA
²Pathology, Vanderbilt University, Nashville, TN

3071

A Single Amino Acid Substitution (I18V) in the Gla Domain of Activated Protein C Markedly Impairs Ability of PE and GlyCer to Enhance Anticoagulant Activity

Jennifer Johnson, BSc¹^*, Fionnuala Ni Ainle, MD¹^*, Shona Harmon, PhD¹^*, James S O'Donnell, MD, PhD² and Roger JS Preston, PhD¹^*

¹Haemostasis Research Group, Trinity College Dublin, Dublin, Ireland
²National Centre for Coagulation Disorders, Dublin, Ireland

3072

Development of a Novel Recombinant Factor VIII Product through Transgene Engineering and Lentiviral-Driven Expression

Keith W Kerstann, PhD¹^*, Pete Lollar, MD²^*, H. Trent Spencer, PhD²^*, Gabriela Denning, PhD¹^*, Lajos Baranyi, PhD³^*, Robert Keefe, PhD³^*, Boro Dropulic, MBA, PhD³ and Christopher B Doering, PhD²

¹Expression Therapeutics, LLC, Tucker, GA
²Emory University School of Medicine, Aflac Cancer Center and Blood Disorders Service, Atlanta, GA
³Administration, Lentigen Corp., Baltimore, MD

3073

Incremental Improvement in Bioengineering of Coagulation Factor VIII for Efficient Expression: Elimination of a Dispensable Disulfide Loop Enhances Secretion

Sundar Rajan Selvaraj, PhD¹^*, Randal J Kaufman, PhD²^* and Steven W. Pipe, MD¹

¹Dept of Pediatrics, University of Michigan, Ann Arbor, MI
²Depts of Biological Chemistry & Internal Medicine, Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI

3074

Size Matters: Differential Effects of RNA and Polyphosphate on Blood Clotting

Stephanie A. Smith, DVM, MS¹ and James H. Morrissey, PhD²

¹Internal Medicine, University of Illinois, Urbana, IL
²Univ. of Illinois College of Med., Urbana, IL

3075

Factor V as Anticoagulant Cofactor for Activated Protein C in Factor Va Inactivation

Thomas J Cramer, MSc.¹^*, John H. Griffin, PhD² and Andrew J. Gale, PhD³

¹Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA
²Scripps Research Institute, La Jolla, CA
³The Scripps Research Inst., La Jolla, CA

3076

Antithrombotic Effects of a FXI Antisense Oligonucleotide in Mice

Hong Zhang, MD¹, Chenguang Zhao¹^*, Jeff Crosby²^*, Curt Mazur²^*, Susan M. Freier²^*, Andy Watt²^*, Andy Siwkowski²^*, Dacao Gao²^*, Chris Black²^* and Brett P. Monia²^*

¹Antisense Drug Discovery, Isis Pharmaceuticals, Inc., Carlsbad, CA
²Isis Pharmaceuticals, Inc., Carlsbad, CA

3077

Regulation of the Gene Encoding Human Thrombin-Activable Fibrinolysis Inhibitor by Female Sex Steroids

Mathieu Garand, M.Sc.¹^*, Michael B Boffa, Ph.D.²^* and Marlys L. Koschinsky, Ph.D.²^*

¹Biochemistry, Queen's University, Kingston, ON, Canada
²Department of Chemistry & Biochemistry, University of Windsor, Windsor, ON, Canada

3078

Regulation of Human Thrombin-Activable Fibrinolysis Inhibitor Gene Expression in Megakaryocyte-Like (Dami) and Monocyte/Macrphage-Like (THP-1) Cell Lines

Joellen H. H. Lin, M.Sc.¹^*, Michael B. Boffa, Ph.D.²^* and Marlys L. Koschinsky, Ph.D.³^*

¹Department of Biochemistry, Queen's University, Kingston, ON, Canada
²Department of Chemistry and Biochemistry, University of Windsor, Windsor, ON, Canada
³Department of Chemistry & Biochemistry, University of Windsor, Windsor, ON, Canada

3079

Hemostatic Factors Support Colitis and Colitis-Associated Colon Cancer

Kris A. Steinbrecher^*, Netanel Horowitz^*, Maureen A. Shaw^*, Kelley A. Barney^*, Matthew J. Flick^*, Eleana Harmel-Laws^*, David P. Witte^*, Elizabeth A. Blevins^* and Joseph S. Palumbo, MD

Cincinnati Children's Hospital Medical Center and The University of Cincinnati College of Medicine, Cincinnati, OH

3080

Antisense Oligonucletide Mediated Depletion of Factor VII Provides Protection from Ferric Chloride Induced Thrombosis without Increased Bleeding Risk in Mice

Jeff Crosby, PhD^*, Chenguang Zhao^*, Dacao Gao^*, Andy Siwkowski^*, Hong Zhang, MD and Brett P. Monia, PhD

Antisense Drug Discovery, Isis Pharmaceuticals, Inc., Carlsbad, CA

3081

Depolymerized Holothurian Glycosaminoglycan Inhibits Plasma Thrombin Generation Via Interaction with the Factor IXa Heparin-Binding Exosite

Buyue Yang¹^* and John P. Sheehan, MD²

¹University of Wisconsin-Madison, Madison, WI
²Dept. of Medicine/Hematology-Oncology, University of Wisconsin, Madison, WI

3082

Factor XI Contributes to Thrombin Generation in the Absence of Factor XIIa

Anton Matafonov¹^*, Dmitri Kravtsov¹^*, Erik I. Tucker²^*, Mao-fu Sun³^*, John P. Sheehan, MD⁴, Andras Gruber, MD² and David Gailani⁵

¹Dept. of Pathology, Vanderbilt University, Nashville, TN
²Division of Biomedical Engineering, Oregon Health and Science University School of Medicine, Portland, OR
³Pathology and Medicine, University of Vanderbilt, Nashville, TN
⁴Medical Sciences Center, University of Wisconsin, Madison, WI
⁵Department of Pathology and Medicine, Vanderbilt University School of Medicine, Nashville, TN

3083

Identification of Hemostatic Modifier Genes Rescuing FVII Deficient Mice

Elliot D. Rosen, PhD¹^*, Valerie A Schroeder, RVT²^*, Zhong Liang, MSc³ and Mark Suckow, DVM²^*

¹Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN
²Freiman Life Science Center, Notre Dame, Notre Dame, IN
³IU School of Medicine, Indianapolis, IN

3084

Inhibition of γ’ Fibrinogen Production in Liver Cells by D-Dimers

Chantelle M Rein, BA¹^*, May-Lynn Chu, BS²^* and David H. Farrell, PhD³

¹Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR
²Department of Pathology, Oregon Health & Science University, Portland, OR
³School of Medicine, L113, Oregon Health & Science Univ., Portland, OR

3085

Endothelial and Hematopoietic Tissue Factor Are Unnecessary in Two Mouse Models of Hemostasis and Thrombosis

Tovo H David^*, David Sulciner^*, Ivo Cornelissen^* and Shaun R Coughlin^*

Cardiovascular Research Institute, UCSF, San Francisco, CA

3086

The Role of N-Linked Glycosylation in Expression and Function of ADAMTS13

Agata Nowak¹^*, Chan Kwo Chion²^*, Michael Laffan¹ and Thomas A J McKinnon³^*

¹Dept. of Hematology, Imperial College School of Med., London, United Kingdom
²Haematology, Imperial College Hammersmith Hospital, London, United Kingdom
³Haematology, Imperial College London, London, United Kingdom

3087

Exploiting ER Stress to Eliminate Inhibitor Antibodies in Hemophilia

Michael U Callaghan, MD¹ and Randal J Kaufman, Ph.D.²^*

¹Hematology/Oncology, Children's Hospital of Michigan, Detroit, MI
²Biological Chemistry, Howard Hughes Medical Institute/University of Michigan, Ann Arbor, MI

3088

An Analysis of Cleavage of the Factor IX Activation Sites by Factor XIa

David Gailani¹, Stephen B. Smith¹^*, Sayeh Agah²^* and S. Paul Bajaj³

¹Department of Pathology and Medicine, Vanderbilt University School of Medicine, Nashville, TN
²Orthopaedic Surgery, UCLA/Orthopaedic Hospital, Los Angeles, CA
³UCLA/Orthopedic Hospital, Los Angeles, CA

3089

Multiscale Mechanics of Fibrin Clots

Andre E.X. Brown¹^*, Rustem I. Litvinov, M.D.²^*, Prashant Purohit³^*, Dennis E. Discher⁴^* and John Weisel⁵^*

¹Physics, University of Pennsylvania, Philadelphia, PA
²University of Pennsylvania School of Medicine, Philadelphia, PA
³Mechanical Engineering and Applied Physics, University of Pennsylvania, Philadelphia, PA
⁴University of Pennsylvania, Philadelphia, PA
⁵Dept Cell & Dev Biology, University of Pennsylvania, Philadelphia, PA

3090

The Factor VIIII C2 Domain Shows Stereospecificity for Phosphatidyl-L-Serine and Increases Factor IXa Activity

Valerie A Novakovic, M.S.¹^*, James D Baleja, Ph.D.²^* and Gary E. Gilbert, MD³

¹Research, VA Boston Healthcare System, West Roxbury, MA
²Sackler School of Biomedical Sciences, Tufts University, Boston, MA
³Medicine and Research, VA Boston Healthcare System, Harvard Medical School, West Roxbury, MA

3091

Procoagulant Activity and Phosphatidylserine of Amniotic Fluid Cells

Jin Zhou¹^*, Shuchuan Liu¹^*, Ming Ma¹^*, Jinxiao Hou¹^*, Hongjuan Yu¹^*, Chengfang Lu¹^*, Gary Gilbert²^* and Jialan Shi²

¹Department of Medicine, Hematology, The First Hospital Affiliated Harbin Medical University, Harbin, China
²Department of Medicine, Hematology, VA Boston Healthcare System, Brigham and Women's Hospital, Harvard Medical School, Boston, MA

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^*signifies non-member of ASH