FIBRINOGEN, THROMBOSIS, COAGULATION, AND FIBRINOLYSIS ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY Editorial Board: NATHAN BACK, State University of New York at Buffalo IRUN R. COHEN, The Weizmann Institute of Science DAVID KRITCHEVSKY, Wistar Institute ABEL LAJTHA, N.S. Kline Institute for Psychiatric Research RODOLFO PAOLETTI, University of Milan Recent Volumes in this Series Volume 274 CIRCULATING REGULATORY FACTORS AND NEUROENDOCRINE FUNCTION Edited by John C. Porter and Daniela Jezova Volume 275 PHOSPHOLIPASE A.: Role and Function in Inflammation Edited by Patrick Y-K Wong and Edward A. Dennis Volume 276 CORONAV IRUSES AND THEIR DISEASES Edited by David Cavanagh and T. David K. Brown Volume 277 OXYGEN TRANSPORT TO TISSUE XII Edited by Johannes Piiper, Thomas K. Goldstick, and Michael Meyer Volume 278 IMMUNOBIOLOGY AND PROPHYLAXIS OF HUMAN HERPESVIRUS INFECTIONS Edited by Carlos Lopez, Ryoichi Mori, Bernard Roizman, and Richard J. Whitley Volume 279 BIOCHEMISTRY, MOLECULAR BIOLOGY, AND PHYSIOLOGY OF PHOSPHOLIPASE A. AND ITS REGULATORY FACTORS Edited by Ani! B. Mukherjee Volume 280 MYOBLAST TRANSFER THERAPY Edited by Robert C. Griggs and George Karpati Volume 281 FIBRINOGEN, THROMBOSIS, COAGULATION, AND FIBRINOLYSIS Edited by Chung Yuan Liu and Shu Chien Volume 282 NEW DIRECTIONS IN UNDERSTANDING DEMENTIA AND ALZHEIMER'S DISEASE Edited by Taher Zandi and Richard J. Ham A Continuation Order Plan is available for this series. A continuation order will bring delivery of each new volume immediately upon publication. Volumes are billed only upon actual shipment. For further information please contact the publisher. FIBRINOGEN, THROMBOSIS, COAGULATION, AND FIBRINOL YSIS Edited by Chung Yuan Liu Institute of Biomedical Sciences Academia Sinica Taipei, Taiwan, Republic of China and Shu Chien University of California, San Diego La Jolla, California SPRINGER SCIENCE+BUSINESS MEDIA, LLC Llbrary of Congress Cataloglng-ln-Publlcatlon Data International Scientific Symposium on Fibrinogen, Thrombosis, Coagulation, and Fibrinolysls (1989 : Taipei, Taiwan) Fibrinogen, thrombosis, coagulat ion, and fibrinolysis ! edited by Chung Yuan Liu and Shu Chien. p. cm. -- (Advances in experimental medicine and biology ; v. 281) "Proceedings of the International Sclentific Symposium on Fibrinogen, Thrombosis, Coagulat ion, and Fibrinolysis, held August 30-September 1, 1989, in Taipei, Taiwan, Republic of Chlna"--T.p. verso. Includes bibliographical references and indexes. ISBN 978-1-4613-6697-3 ISBN 978-1-4615-3806-6 (eBook) DOI 10.10071978-1-4615-3806-6 1. Blood--Coagulation--Congresses. 2. Fibrinogen--Congresses. 3. Fibrinolysis--Congresses. 4. Thrcmbosis--Congresses. 1. Liu, Chung Yuan, 1934- II. Chien, Shu. III. Title. IV. Series. [DNLM: 1. Blood Coagulation--physiology--congresses. 2. Coronary Thrombosis--drug therapy--congresses. 3. Endocardium--cytology- -congresses. 4. Fibrlnogen--physiology--congresses. 5. Myocardial Infarction--drug therapy--congresses. 6. Thrombolytic Therapy- -congresses . W1 AD559 v. 281 I WH 310 15975f 19891 OP93 . 5.1538 1989 612. l' 15--dc20 DNLM / DLC for Library of Congress 90-14299 CIP Proceedings of the International Scientific Symposium on Fibrinogen, Thrombosis, Coagulation, and Fibrinolysis, held August 30-September 1, 1989, in Taipei, Taiwan, Republic of China )SBN 978-1-4613-6697-3 © 1990 Springer Science+Business Media New York Originally published by Plenum Press in 1990 Softcover reprint of the hardcover Ist edition 1990 AII rights reserved No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher PREFACE The International Scientific Symposium on Fibrinogen, Thrombosis, Coagulation, and Fibrinolysis was held in Academia Sinica, Taipei, Taiwan, Republic of China, on August 30 - September 1, 1989. This Symposium has provided a forum for the free exchange of information in this important and rapidly advancing research field. This proceedings volume provides a published record of 46 papers presented at the Symposium. The sponsors have exerted no influence on the scientific opinions or positions of the participants in the Symposium. It is hoped that this Symposium will stimulate further worldwide cooperation and collaboration in these vital fields for the benefit of all human kind. This volume is composed of four parts. The first part consists of 8 papers on Fibrinogen and Fibrin: Biochemistry, Molecular Biology, and Physiology. The second part contains 16 papers on Coagulation and Fibrinolysis: Biochemistry, Molecular Biology, and Physiology. The third part has 10 papers on Cardiovascular Cell Biology: Biochemistry, Molecular Biology, and Physiology. The fourth part comprises 12 papers on Clinical Studies of the Cardiovascular System: Thrombotic and Bleeding Disorders and Thrombolytic Therapy. The Author Index with addresses of all contributors and the Subject Index of all 46 papers are arranged at the end of this volume. On behalf of the Symposium Organizing Committee, it is indeed our pleasure to sincerely thank all of the participants for their participation in the Symposium. We ap- preciate very much the valuable contributions by the distinguished scientists coming from many nations around the world and the Republic of China as speakers and chairpersons of scientific sessions in this Symposium and as members of Symposium Committees. Their participation has assured the high quality of the Symposium. We would like to acknowledge with sincere gratitude the support and encouragement by the sponsors of this Symposium: Academia Sinica, National Science Council, Depart- ment of Health, and fourteen Scientific Societies, and the co-sponsors: the Foundation for Biomedical Sciences and the China Committee for Scientific and Scholarly Cooperation with U.S.A. We also wish to express our appreciation for the generous support from several government agencies and private sectors of the Republic of China toward this Symposium. The organization of the Symposium was initiated about one year before the 60th an- niversary of Academia Sinica of the Republic of China (June 9, 1988), and the Symposium was held about one year after the Anniversary. We have dedicated this Symposium to Academia Sinica as a part of its 60th anniversary celebration, and we would also like to dedicate this proceedings volume to this anniversary. To our colleagues in the scientific and medical communities of the Republic of China and the staff members of the Institute of Biomedical Sciences (IBMS) of Academia Sinica we wish to extend our deepest appreciation for their marvelous efforts, total dedication and wonderful cooperation and for giving us a most rewarding and memorable Symposium. We would like particularly to acknowledge the important contributions by Ms. Jenny Chen and Ms. Maggie Shih of IBMS for their assistance in planning for this proceedings volume, by Ms. Grace Han of Enjoy Enterprise Co., Ltd. in Taipei for her help in retyping the entire volume, and by the staff of Plenum Publishing Corporation in New York for their suggestions, comments and assistance in general for the organization and publication of this volume. Shu Chien, Ph.D., M.D. Chairman Chung Yuan Liu, Ph.D. Secretary General Symposium Organizing Committee July 30, 1990 v CONTENTS PART I FIBRINOGEN AND FIBRIN Biochemistry, Molecular Biology, and Physiology Native Fibrin Gel Networks and Factors Influencing their Formation in Health and Disease .................................................................................... . B. Blombiick, D. Banerjee, K. Carlsson, A. Hamsten, B. Hessel, R. Procyk, A. Silveira, and L. Zacharski The Structure and Evolution of Vertebrate Fibrinogen: A Comparison of the Lamprey and Mammalian Proteins ....................................................... 25 Russell F. Doolittle Nucleotide Sequences of the Three Genes Coding for Human Fibrinogen ................. 39 Dominic W. Chung, Jeff E. Harris, and Earl W. Davie On the Identity of Fibrin(ogen) Oligomers Appearing During Fibrin Polymerization ................................................................................. 49 Agnes Henschen Immunochemical Studies of Aa Chain Crosslinking .............................................. 55 Joan H. Sobel and Robert E. Canfield Abnormal Fibrinogens with Two Structural Defects .............................................. 63 Michio Matsuda, Shigeharu Terukina, Nobuhiko Yoshida, Kensuke Yamazumi, and Hisato Maekawa Electrophoretic Characterizations of Cross-Linked Fibrinogen Derivatives in Blood and Vascular Tissue by Zonal Immobilization on Glyoxyl Agarose ............. 73 John R. ShainofJ, Rafael Valenzuela, Robert Graor, David A. Urbanic, and Patricia M. DiBello Studies on the Localization and Accessibility of Sites in Fibrin which Are Involved in the Acceleration of the Activation of Plasminogen by Tissue-Type Plasminogen Activator ....................................................................... 83 W. Nieuwenhuizen, W.J.G. Schielen, O. Yonekawa, G. I. Tesser, and M. Voskuilen PART II COAGULATION AND FIBRINOLYSIS Biochemistry, Molecular Biology, and Physiology A COAGULATION Prothrombinase: Recognition and Developments ................................................. 93 Walter H. Seegers The Initiation of the Tissue Factor Dependent Pathway of Blood Coagulation .......... 97 Samuel I. Rapaport vii Interactions Between the Contact System, Neutrophils and Fibrinogen ..................... 105 Robert W. Colman A New Trisaccharide Sugar Chain Linked to a Serine Residue in the First EGF-Like Domain of Clotting Factors VII and IX and Protein Z ............................ 121 Sadaaki Iwanaga, Hitoshi Nishimura, Shun-ichiro Kawabata, Walter Kisiel, Sumihiro Hase, and Tokuji Ikenaka Multiple Epitope Specificity of Monoclonal Antibodies to a Single Synthetic Peptide: Use in the Characterization of the GP lIb-IlIa Binding Domain of von Willebrand Factor ....................................................................... 133 Shlomo A. Berliner, Richard A. Houghten, James R. Roberts, and Zaverio M. Ruggeri Factor VII and Dietary Fat Intake .................................................................... 145 G. J. Miller, J. C. Martin, K. A. Mitropoulos, and J. K. Cruickshank Characterization of Snake Venom Principles Affecting Blood Coagulation and Platelet Aggregation .................................................................... 151 Chaoho Ouyang, Che-Ming Teng, and Tur-Fu Huang Thrombin-Like Venom Enzymes: Structure and Function ..................................... 165 Hubert Pirkle and Ida Theodor Thrombin Inhibition by Synthetic Hirudin Peptides .............................................. 177 John M. Maraganore and John W. Fenton II B FIBRINOLYSIS Effects of Structural Modifications on the Properties of Tissue Plasminogen Activator (tPA) ................................................................................ 185 Per Wallen, Xiang-Fei Cheng, and Per-Ingvar Ohlsson Molecular Genetics of Alpha 2 Plasmin Inhibitor ................................................. 195 Nobuo Aoki Biological Properties of Hybrid Plasminogen Activators ........................................ 201 P. P. Hung, J. Wilhelm, N. K. Kalyan, S. M. Cheng, H. L. James, D. Nachowiak, C. J. Weinheimer, B. E. Sobel, S. R. Bergmann, and S. G. Lee The Regulation of the Activaton of the Fibrinolysis System ................................... 209 A. Takada, T. Urano, and Y. Takada The Mechanisms of the Activation of Plasminogen by Streptokinase and Urokinase .................................................................................. 223 Yumiko Takada and Akikazu Takada Protein C and Fibrinolysis: A Link Between Coagulation and Fibrinolysis ............... 235 N. J. de Fouw, F. Haverkate, and R. M. Bertina Transformation of Prostacyclin (PGIJ to a Biologically Active Metabolite: 5(6)-Oxido-PGI1 by Cytochrome P450-Dependent Epoxygenase .................. 245 Patrick Y.-K. Wong viii PART III CARDIOVASCULAR CELL BIOLOGY Biocbemistry, Molecular Biology, and Pbysiology A PLATELETS Studies on the Localization of Fibrinogen Binding Sites on Platelet Glycoprotein IlIa .............................................................................. 251 Stefan Niewiarowski, Karin J. Norton, Jacquelynn J. Cook, and Annette Eckardt Affinity Labeling of Nucleotide Binding Sites of Enzymes and Platelets ................... 257 Roberta F. Colman The Effect of Ganodermic Acid S on Human Platelets ......................................... 265 Chuen-Neu Wang, Jia-Chyuan Chen, Ming-Shi Shiao, and Cheng-Teh Wang Role of Insulin Receptors in the Expression of Prostaglandin EJ Binding Activity in Platelets ...................................................................................... 271 Nighat N. Kahn and A. Kumar Sinha Platelet-Fibrin Interaction in the Suspension and Under Flow Conditions ................. 277 C. J. Jen, S. J. Hu, H. J. Wu, T. S. Lin, and C. W. Mao An Independent Haemostatic Mechanism: Shear Induced Platelet Aggregation ......... 287 J. R. O'Brien and G. P. Salmon B ENDOTHELIAL CELLS AND VESSEL WALL Regulation of Eicosanoid Biosynthesis in Endothelial Cells: Critical Role of De Novo Synthesis of Prostaglandin Endoperoxide Synthase ..................... 297 Kenneth Kun- Yu Wu Modulation of Endothelial Function by Hypoxia: Perturbation of Barrier and Anticoagulant Function, and Induction of a Novel Factor X Activator ....... 303 Satoshi Ogawa, Revati Shreeniwas, Caesar Butura, Jerold Brett, and David M. Stern Fibrin and the Vessel Wall .............................................................................. 313 K. L. Kaplan, A. Bini, J. Fenoglio, Jr. and B. Kudryk Interactions between Fibrin, Collagen and Endothelial Cells in Angiogenesis ............. 319 H. Mei Liu, Danny Ling Wang, and Chung Yuan Liu PART IV CLINICAL STUDIES OF THE CARDIOVASCULAR SYSTEM Thrombotic and Bleeding Disorders and Thrombolytic Therapy New Developments in Thrombolytic Therapy ...................................................... 333 D. Collen and H. K. Gold Coronary Thrombosis: Pathogenesis and Prevention ............................................ 355 G. V. R. Born ix Implications of the TIMI Trials ........................................................................ 361 Allan M. Ross Thrombotic Microangiopathy ........................................................................... 367 Hau C. Kwaan Clinical Trials with Alteplase (RT-pa) in Acute Myocardial Infarction ..................... 377 David P. de Bono The Effects of Streptokinase and Tissue Plasminogen Activator on Left Ventricular Function ......................................................................... 383 Harvey D. White Modern Strategies for Treatment of Acute Myocardial Infarction: Significance of Haemostaseological and Rheological Findings .................... 389 G. Pindur, C. Sen, E. Wenzel, F. Jung, C. Ozbek, H. Schwerdt, H. Schieffer, L. Bette, and C. Miyashita Clinical Application of Tissue Plasminogen Activator Therapy in Acute Myocardial Infarction ........................................................................ 395 Shih-Pu Wang, Mau-Song Chang, and Benjamin N. Chiang Fibrinogen Proteolysis and Coagulation System Activation During Thrombolytic Therapy ....................................................................... 401 John Owen, Betty Grossman, Joan Sobel, and Bohdan Kudryk Altered Rheological Properties of Blood Following Administrations of Tissue Plasminogen Activator and Streptokinase in Patients with Acute Myocardial Infarction ......................................................................... 409 Kung-ming Jan, Eric Powers, Walter Reinhart, Andrew Berke, Allen Nichols, Rita Watson, Dennis Reison, Allan Schwartz, and Shu Chien Monoclonal Antibodies for the Detection of Thrombosis ....................................... 419 P. J. Gaffney, P. S. Gascoine, L. J. Creighton, and P. M. Tymkewycz The Pharmacology and Clinical Pharmacology of Defibrotide: A New Profibrinolytic, Antithrombotic, and Anti-Platelet Substance .......... 429 O. N. Ulutin, S. Balkuv-Ulutin, M. S. Ugur, T. Ulutin, Y. Ozsoy, and G. Cizmeci AUTHOR INDEX ............................................................................................. 439 SUBJECT INDEX ............................................................................................. 447 x NATIVE FIBRIN GEL NETWORKS AND FACTORS INFLUENCING THEIR FORMATION IN HEALTH AND DISEASE B. Blomback a,b, D. Banerjeeb, K. Carlssonc, A. Hamstend, B. Hessela , R. Procykb, A. Silveiraa, and L. Zacharskie aKarolinska Institutet, S-10401 Stockholm, Sweden, bThe New York Blood Center, New York, NY 10021, USA, 'The Royal Institute of Technology, S-10444 Stockholm (Sweden), dKing Gustaf V Research Institute, Karolinska Hospital, S-10401 Stockholm and 'Veterans Administration Hospital, White River Junction, VT 05001, USA SUMMARY Hydrated fibrin gels were studied by confocal laser 3D microscopy, liquid permeation and turbidity. The gels from normal fibrinogen were found to be composed of straight rod-like fiber elements which sometimes originated from denser nodes. In gels formed at increasing thrombin or fibrinogen concentrations, the gel networks became tighter and the porosity decreased. The fiber strands also became shorter. Gel porosity of the network decreased dramatically in gels formed at increasing ionic strengths. Shortening of the fibers were observed and fiber swelling occurred at ionic strength above 0.24. Albumin and dextran, when present in the gel forming system, affected the formation of more porous structures with strands of larger mass-length ratio and fiber thickness. This type of gels were also formed in plasma. Albumin and lipoproteins may be among the determinants for the formation of this type of gel structure in plasma. Gels formed when factor XlIIa instead of thrombin was used as catalyst for gelation showed a completely different structure in which lumps of polymeric material were held together by a network of fine fiber strands. Our studies have also shown that the methodologies employed may be useful in studies of gel structures in certain dysfibrinogenemias as well as in other diseases. We give exam- ples of two patients with abnormal fibrinogen and of patients with ischaemic heart disease. INTRODUCTION Extensive knowledge of the structure of fibrinogen and the formation and pi ~'perties of fibrin polymers has been accumulated during the past decades through studies em- ploying chemical and physicochemical methods (1, 2, 3). The fibrinogen molecule is an asymmetric rod-shaped dimer (about lOx45 nm). On activation, the fibrinogen molecules polymerize by end-to-end and side-to-side association there by forming protofibrils. The protofibrils associate to form fibrin fibers and the latter join into bundles of larger widths. Protofibrils were suggested to be twisted in a helical fashion (4, 5, 6). The twisting is possibly a reflection of an indigenous screw symmetry in the fibrinogen molecule itself. Fibrin fibers, also twisted, were seen to grow to a limiting size (7, 8). The limitation in growth was explained as a consequence of stretching of the proto fibrils near the surface of the fiber. When the amount of energy necessary to stretch Fibrinogen, Thrombosis, Coagulation, and Fibrinolysis, Edited by C. Y. Liu and S. Chien, Plenum Press, New York