A rapid increase in our understanding of the biology of platelets and their role in disease in recent years has been paralleled by increasing successes with established platelet-modifying therapies in many clinical conditions. This text focuses on the clinical role of platelets in a wide variety of haematologic, cardiovascular and other disorders, providing a practical, clinically relevant handbook for all clinicians and researchers interested in platelets and their role in disease. Covering platelet physiology, bleeding disorders, thrombotic disorders and antithrombotic therapy. Chapters cover all the conventional and less conventional aspects of platelet involvement in disease, with an emphasis on recent clinical developments. Clear take home messages have been included in each chapter to aid clinical practice. With contributions from leading experts across three continents, Platelets in Hematologic and Cardiovascular Disorders is an up-to-date, well illustrated, practical resource for everyone involved in clinical practice with platelet disorders.

This volume constitutes the proceedings of a satellite symposium of the XXXth congress of the International Union of Physiological Sciences. The symposium has been held In Banff, Alberta Canada July 9-11 1986. The program was organized to provide a selective overview of current developments in cardiac biophysics, biochemistry, and physiology. In order to highlight areas of develop ing ideas and to stimulate the participants' inquisitiveness into the nature and complexity of the integrated cardiovascular system, lectures and discussions were presented that emphasized evolving and sometimes provocative concepts in the field. With the same goal in mind we have, for the readers of this volume, briefly summarized the general discussions. We would like to thank several individuals whose dedication made this sym posium and publication of the proceedings possible. Mrs. Lois Kokoski and Mrs. Madeleine Aldridge of the Conference Office of the University of Calgary seemingly effortlessly handled the details of the symposium. Peter de Tombe, Dr. Peter Backx and Dr. Jeroen Bucx transcribed the general discussions. Finally, we appreciate the extra effort of our secretaries, Lenore Doell and Gregory Douglas, and the work of Anna Tyberg who prepared the final manuscripts for publication. Henk E.D.J. ter Keurs, M.D. Ph.D. John V. Tyberg, M.D. Ph.D."

Haemoglobin is one of the most important molecules in the animal kingdom. Its function is to carry oxygen to tissues. In lower invertebrates the blood pigment is present in the haemolymph and is not bound in cells. Later in the course of phylo genesis haemoglobin remains associated with cells which produce it and in this form it reaches the peripheral circulation. In higher organisms the haemoglobin production is thus determined by two main factors: haemoglobin synthesis in erythroid cells and the formation of these erythroid cells which depends on cell proliferation in haematopoietic organs. Human haemoglobin is made up of two chains which combine from four different polypeptide chains formed in varying ratios in different periods of the life cycle. During the life span of humans the following haemoglobins are formed: embryonic haemoglobins Gower 1 and 2, foetal haemoglobin F and two adult haemoglobins A and A . E-and IX-chains are part of the embryonic haemoglobins Gower 1 (E4) and 2 Gower 2 (1X2E2). These haemoglobins predominate in embryos during the second month of pregnancy and at the end of the first trimester they are completely re placed by foetal haemoglobin F ( Y2). Adult haemoglobin A consists of two IX and two -chains and is the main component of red cells in adults. A relatively small component of red cells accounting for less than 2 % of the total haemo globin, is haemoglobin A2 (1X0)."

This volume comes from manuscriptscontributed by invited speakers to the NATO AdvancedStudyInstitute on Biopolymers, which was held in Izmir, during August 27th - September 5th, 1984. Many more detailshave been added to the manuscripts as a resultof the interchange of ideas during the symposium. This book includes 16 papers which were originallypresented at the meeting by some of the world'sforemostinvestigators. In this volume, the existing basic knowledgeacross the wholefieldof polymericbiomaterials is reviewed.Classification, structure, composition, synthesis, modification and fabrication of these novel materialsis included in detail. Fundamental phenomena involved in the interactionof polymers with the biological environmentand resultingresponses of blood and tissue components are discussed. Modification of polymers physically, chemicallyor biochemically, in order to improve their biocompatibility is included. Selected applications of polymeric biomaterialsin Medicine, Dentistry, Biotechnology, Pharmacology and otherrelated fieldsarealsocovered. We stronglyhope thatthis book will be agreatcontribution to the rapidly expanding field of biomaterialsand willhelp to stimulate an even more excitingfuturefor th is field. ErhanPiskin AllanS. Hoffman VI ACKNOWLEDGEMENTS NATO Advanced Study Institute on "Biopolymers" was held in Izmir during August 27th - September 5th, 1984. I would like to ex press my deepest appreciation and gratitude to NATO Scientific Affairs Division, that our meeting has been accepted as a NATO ASI, and has been supported by their programmes. I wish to thank also to all the other supporting firms and organizations, especially to Hacettepe University and Turkish Scientific and Technical Research Council."

vitro methodology for the cultivation of erythroid The purpose of In Vitro Aspects of Erythropoiesis is to broaden our understanding of the regulation of stem cells. The second series of papers treats cellular normal and neoplastic hematopoietic cells by means and soluble factors which affect erythroid stem cell of a synthesis of different techniques, divergent no- differentiation. Hormonal modulation of in vitro menclature as well as a closer standardization of re- erythropoiesis is the theme of the third session fol- agents and methods which had heretofore produced lowed by a series of papers in the fourth which fo- vagaries of results among different laboratories. cuses on erythropoiesis after transformation by ei- Hence the papers, discussions and appendices pre- ther Friend or Rauscher viruses. The fifth session deals with serum inhibitors to erythropoiesis and the sented in this volume will be of value and interest to investigators and clinicians as well as to students and role of the macrophage in red blood cell production. teachers of hematology. Finally, the sixth session concentrates on the biogen- In Vitro Aspects of Erythropoiesis is comprised of esis of erythropoietin in vivo and in vitro. thirty papers delivered by twenty invited contribu- Each of the six sections is followed by a discus- tors at a three day conference which was held in sion which was transcribed and initially edited at the Capri, Italy in October of 1977. The contributors meeting.

Some three decades after bone marrow transplantation was introduced in the field of hematology and oncology, transplantation today continues to rapidly grow and expand into a variety of new modalities. Peripheral blood has been established as an effective source of autologous progenitor cells. Furthermore, the graft-versus-leukemia effect has resulted in novel strategies of adoptive immunotherapy for cancer. Finally, approaches to gene transfer and therapy are utilizing transplantation methodologies and can augment their effects. Current results, new developments and perspectives are presented in this volume. Conventional and innovative experimental approaches, the past and the future of bone marrow transplantation are reviewed and discussed by leading representatives.

This symposium is devoted to Biotechnology in Blood Transfusion; there are 22 experts discussing the state of the art in the application of monoclonal anti bodies, recombinant DNA technologies and heterologous expression systems to the improvement and sometimes replacement of blood products, charac terization of blood constituents, and the effect of these developments on blood transfusion procedures. Ten and maybe five years ago the title of a symposium such as this would have been Biosciences in blood transfusion, informing what basic developments in molecular biology, biochemistry and human physiology might pertain to blood transfusion in the distant future. That future is getting closer, and not only one is interested in basic developments in immunology, recognition and identification of viral and bacterial components and products, tissue and blood bloodgroup blood group typing, typing, but also in the potential application of these developments and their economic perspectives. That is what biotechnology is all alI about: basic science telIs tells us where and how we might look for new technologies, and the development of such tech nologies is only possible if there is a perspective for improvement in quality, safety, acceptance or performance to cost ratio.

Siegmund J. Baum It has become a tradition to commence advocated by Leonard Cole) (3). important meetings of this society with At about the same time, Alpen and reminiscence and nostalgia. Bone marrow Baum (4), using a larger mammal, the dog, transplantation, which has a history of only demonstrated that injecting autologous marrow 30 to 40 years, permits this process, since post irradiation would protect lethally some of the early investigators are still with irradiated animals (see Table). Certainly, us. For example, over the past 15 years, we protection was obtained from the cellular have had three symposia in honor of Egon constituents of the bone marrow. Lorenz. As we all know, the team of Lorenz, We undertook to test on dogs the Uphoff and Congdon was involved in the first hypothesis of Gengozian and Makinodum (5) that successful transplantation of syngeneic and increasing the radiation dose will increase allogeneic bone marrow into irradiated immunologic tolerance for allogeneic implants.

Proceedings of the Tenth Annual Symposium on Blood Transfusion, Groningen 1985, organized by the Red Cross Blood Bank Groningen-Drenthe

This volume reports the proceedings of a NATO Advanced Workshop held at Cameron House Hotel, Loch Lomond, Scotland, from May 2 - 5, 1994. The major impetus for this workshop was the realisation, over the past 7 years, that the Epstein-Barr virus is associated with a proportion of cases of Hodgkin's disease and is likely to play an aetiological role. There were four main aims of the workshop: first, to discuss the recent findings in relation to Epstein Barr virus and the aetiology of Hodgkin's disease; second, to relate these data to the epidemiology of Hodgkin's disease; third, to discuss other potential aetiological factors and finally, to discuss future directions for research into Hodgkin's disease. Leading experts in the field have contributed chapters to this volume. There is some overlap among chapters, particularly regarding Epstein-Barr virus, thereby allowing different groups to express views on similar topics. Perhaps, however, the most surprising feature of the workshop was the lack of controversy regarding the role of Epstein-Barr virus in Hodgkin's disease, an association that was treated with great scepticism at the beginning of the decade. The first three chapters, by Alexander, Taylor et al., and Levine el al., discuss the epidemiology of Hodgkin's disease with particular attention to clustering and genetic susceptibility. These chapters represent the first attempt to bring together epidemiological and molecular studies in Hodgkin's disease.

THE PHILOSOPHY OF QUALITY ASSURANCE IN THE BLOOD BANK H. F. Taswell One year before this symposium, Cees Smit Sibinga and I began to discuss an approach to quality assurance in the blood bank which we felt would be both important and practical and could serve as the basis for the choice of subjects to be presented in the symposium. As an introduction to this book, I would like to outline our approach, the subjects chosen and the rationale behind our choice. What is the fundamental purpose of a blood bank and trans fusion service? Simply stated, the purpose of a blood bank and transfusion service and of a quality assurance program in blood banking is, for the one to provide and, the other to assure safe and effective transfusion therapy. This objective is in contrast to that of other clinical laboratories. The objective in a clinical chemistry laboratory is to produce accurate test results which will be meaningful to the clinician taking care of his patient. In most clinical laboratories, therefore, the goals of a quality assurance program are largely quantitative, that is, to assure accurate numerical test results. In contrast, in the blood bank, the goals of quality assurance are primarily qualitative, that is, to assure safe and effective transfusion. As a result, two somewhat different approaches to quality assurance are necessary.

David Kuter and a host of leading international researchers summarize in one volume all the knowledge of thrombopoietins (TPO) available today. The distinguished experts review the history of the search to discover TPO, describe the molecular and biological characteristics of this new molecule, and present the results of the preclinical animal experiments that will guide clinical use of this new hormone. Along the way they provide the most recent and comprehensive guide to the biology of megakaryocytes and platelets.

It is an honour and a pleasure to welcome you all at this 20th annual International Symposium on Blood Transfusion in the Netherlands. This year you celebrate its 20th anniversary and I congratulate the Staff of the Blood Bank Noord Nederland and especially Dr. Smit Sibinga for this great achievement. As most of you know, the name of the person of Dr. Smit Sibinga is unbreakably con nected with the annual symposium in Groningen which he has organized each year from the very start, 20 years ago. The reputation of any symposium depends heavily on the quality of the lectures. I think it is not possible to organize 20 symposia in a row if the topics lack actual relevance and the speakers are not of excellent reputation. Dr. Smit Sibinga has proven to have a keen eye for selecting interesting themes and eminent speakers. Although a lot of different topics have been dealt with in the past 20 years, which each attracted the attention of a different group in the field of blood transfusion, it is not surprising that after a tradition of 20 years several speakers but also a lot of attendees are not for the first time in Groningen to participate in this event. It gives the symposium a unique atmosphere of intimacy. It is not hard to admit that most of the newer developments in transfusion medicine take place outside the Netherlands."

This major new comprehensive guide focuses on particular topics in the field of nutritional anemias, with in-depth coverage on each relevant nutrient whose deficiency can cause anemia, their metabolism, dietary requirements and related information. This book presents the unique hematological, and non-hematological, manifestations of each deficiency, the varied settings and causes of deficiency, interactions with other problems, diagnostic approaches and tools, synthesizing the perspectives of epidemiology, public health, and clinical hematology. Covering approaches to medical management in individuals, as well as in susceptible populations such as children, pregnant women and the elderly; and preventive strategies, such as supplementation and fortification, this exceptional text will appeal to a wide audience, from the clinician learning about the epidemiology and public health aspects of food fortification, to the public health practitioner who needs to understand clinical approaches to key nutritional anemia issues.

Red blood cells in humans-and most other mammals-have a tendency to form aggregates with a characteristic face-to-face morphology, similar to a stack of coins. Known as rouleaux, these aggregates are a normally occurring phenomenon and have a major impact on blood rheology. What is the underlying mechanism that produces this pattern? Does this really happen in blood circulation? And do these rouleaux formations have a useful function? The first book to offer a comprehensive review of the subject, Red Blood Cell Aggregation tackles these and other questions related to red blood cell (RBC) aggregates. The book covers basic, clinical, and physiological aspects of this important biophysical phenomenon and integrates these areas with concepts in bioengineering. It brings together state-of-the-art research on the determinants, mechanisms, and measurement and effects of RBC aggregation as well as on variations and comparative aspects. After an introductory overview, the book outlines factors and conditions that affect RBC aggregation. It presents the two hypotheses-the bridging model and the depletion model-that provide potential mechanisms for the adhesive forces that lead to the regular packing of the cells in rouleaux formations. The book also reviews the methods used to quantify RBC aggregation in vitro, focusing on their importance in clinical practice. Chapters discuss the effect of RBC aggregation on the in vitro rheology of blood as well as on tube flow. The book also looks at what happens in the circulation when red blood cells aggregate and examines variations due to physiological and pathophysiological challenges. The concluding chapter explores the formation of red blood cell aggregates in other mammals. Written by leading researchers in the field, this is an invaluable resource for basic science, medical, and clinical researchers; graduate stu

The colony-stimulating factors (CSFs) are the major regulators in the body of the production and activity of two types of white blood cells--granulocytes and macrophages. CSFs are used by clinicians to treat patients with damaged immune systems, for example, as a result of chemotherapy. This book provides a detailed and up-to-date account of the discovery of the CSFs, their structure, molecular biology and cellular receptors, the biology of the CSFs in vivo and in vitro, and their present and future clinical applications. Written by two of the pioneers in the discovery of CSFs, it is a clear and well illustrated survey of the history, current knowledge and future directions of this exciting field of investigation, and serves also as a guide to the more general areas of growth factor and cytokine research. It will prove an invaluable review for cell biologists interested in how growth factors act on the body, as well as for clinicians applying the fruits of modern biotechnology to improved patient care.

51 worldwide leading experts in the field of erythrocyte research contributed to this first book on transport processes in red blood cells. It explains the latest findings on the basis of well-established principles, in an accessibly structured and carefully organized compilation.

Is the nephrology community facilitating excess cardiovascular deaths in patients with kidney failure and anemia by treating to a subnormal hematocrit? Why have clinicians and nephrologists permitted health insurance companies and the government to decide when anemia therapy should begin in persons with progressive kidney failure? Is iron the only variable that can be manipulated to maximize response to recombinant erythropoietin? Are we using too much intravenous iron in kidney failure patients, and is oral iron supplementation worthless in sustaining iron stores during long-term erythropoietin treatment? When does left ventricular hypertrophy begin to emerge in patients with progressive renal disease and is there convincing evidence that anemia is a significant cause of LVH in this setting? Is darbepoetin alfa, a new novel, long-acting erythropoietin, really superior to recombinant erythropoietin? This book is a compilation of proceedings from a conference in Brooklyn convened to address these and other controversial and unresolved issues in renal anemia management.

It is with great pleasure that I write this Foreword to the Proceedings of the International Conference on Behcet's Disease which was held in Berlin in June 2002. This was the first International Conference held under the auspices of the International Society for Behcet's Disease which was founded in 2000 in Seoul. First, I congratulate our colleagues in Berlin, led by Professor Christos Zouboulis of the Department of Dermatology at the Free University of Berlin, for having organised a most successful conference and for having compiled these proceedings so rapidly. It will be realised immediately on scanning the contents of this book that the conference was truly international with 210 participants from 26 countries, as Professor Zouboulis has noted in his preface. These included basic scientists, epidemiologists, pathologists, clinicians and, importantly, representatives from patient organisations. The latter held their own conference alongside the scientific-medical conference to mutual benefit. The combined session of patients and doctors (abstracts on pp 601 - 626) gave the opportunity for an exchange of information and fruitful discussion. The wide ranging scope of the communications is evident from the index and it was most encouraging to see their origin - from all parts of the world, from senior and junior colleagues and, from many different disciplines. Many communications may be regarded as preliminary reports of research in progress and we look forward to seeing the definitive publications in appropriate journals in due course."

This book describes all human leukemia-lymphoma cell lines that have been established and that grow continuously under standardised in vitro conditions. These lines are derived from cells belonging to all the major hematopoietic cell lineages, i.e. B- and T-lymphocytes, natural killer cells, granulocytic cells and megakaryocytic cells. The clinical data, the culture conditions and the major phenotypic features of the cell lines are described with citations. This book is the first book describing human leukemia-lymphoma cell lines and will be of interest to scientists involved in the areas of hematology, oncology, immunology, molecular biology and cytogenetics. Cancer Cell Lines, Volumes 1-3: These 3 volumes provide a comprehensive text on the culture of established cell lines from every type of human cancer. The volumes provide a basic manual and reference resource for every cancer research scientist using human cancer cells.

Welcome to the City of Groningen, the center of the North of the Netherlands. Groningen is proud of the long lasting tradition of scientific symposia organised by the Sanquin Blood Bank. These Sanquin International Symposia on Blood Transfusion have become a true traditional event in Groningen, marking the early academic year and have contributed to the specific reputation of Groningen and its University in the scientific field of Transfusion Medicine. The growing tradition has also contributed to initiatives of both University, Province and the City of Groningen to bring science and industry together - BioMedCity Groningen. Such repu- tion does not just happen, but is the result of creative and scientific leadership, of vision and an open mind, to explore in a team spirit horizons. Groningen is particularly proud of this reputation thanks to its leadership, the Sanquin Blood Bank North-East. This year in particular the theme chosen some two years ago is extremely timely as it illustrates the activities and scientific interest of an integrated team which includes our regional Sanquin Blood Bank North-East and fits in the City initiatives within the concept of BioMedCity, Groningen.

Mononuclear phagocytes, which include macrophages, monocytes and their precursor cells, are the most important cells in the host defence against micro-organisms and tumor cells. During the last twenty-five years research on the biology of mononuclear phagocytes has increased tremendously. This motivated Professor R. van Furth to organize five international conferences on this subject in Leiden, the Netherlands. The edited proceedings of these meethings were published: in 1970 Mononuclear Phagocytes; in 1975 Mononuclear Phagocytes in Immunity, Infections and Pathology; in 1980 Mononuclear Phagocytes -- Functional Aspects; and in 1985 Mononuclear Phagocytes -- Characteristics, Physiology and Function. Reviews of these volumes, published in international journals, praised them as the most up-to-date state of the art publications. The publication of 1991 includes 88 chapters written by more than 200 authors.

Proceedings of the Twenty-Eighth International Symposium on Blood Transfusion, Groningen, NL, Organized by the Sanquin Division Blood Bank North-East, Groningen.

It is in many ways fitting that the last of these international symposia on blood transfusion should end with neonatal blood transfusion. The most fragile, least well studied and most at risk population requires special care and concern. We need to expand our knowledge of their unique physiology, biochemical pathways and in planning treatment and interventions, always "do no harm."

This proceedings of the last Groningen symposium presents a wealth of information on developmental immunology, the molecular basis of haematopoeisis, physiological basis of bleeding and thrombosis, transfusion risks and benefits and lastly, future therapies. Infants provide us with much to learn but in turn they will be the providers of (through cord blood) and the recipients of (through cellular engineering) the best that science can offer. Translational research, which has been the thrust of these presentations for 28 years, will benefit them in a way that no scientist could have ever predicted.

12 The average human body has on the order of 10 circulating platelets. They are crucial for hemostasis, and yet excessive platelet activation is a major cause of m- bidity and mortality in Western societies. It is therefore not surprising that platelets have become one of the most extensively investigated biological cell types. We are, however, far from understanding precisely how platelets become activated under physiological and pathophysiological conditions. In addition, there are large gaps in our knowledge of platelet production from their giant precursor cell, the megakar- cyte. Understanding megakaryocyte biology will be crucial for the development of platelet gene targeting. The aim of Platelets and Megakaryocytes is therefore to bring together established and recently developed techniques to provide a comprehensive guide to the study of both the platelet and the megakaryocyte. It consists of five s- tions split between two volumes. The more functional assays appear in Volume 1, whereas Volume 2 includes signaling techniques, postgenomic methods, and a n- ber of key perspectives chapters. Part I of Volume 1, Platelets and Megakaryocytes: Functional Assays, describes many well-established approaches to the study of platelet function, including aggregometry, secretion, arachidonic acid metabolism, procoagulant responses, pla- let adhesion under static or flow conditions, flow cytometry, and production of microparticles. Although one would ideally wish to perform experiments with human platelets, studies within the circulation using intravital microscopy require the use of animal models, which are described in Chapter 16, vol. 1.

During the past few decades, technical and conceptual breakthroughs have led to a virtual revolution in developmental biology. In part through cross-species compa- sons and multidisciplinary approaches (combining, for example, classical embry- ogy, genetics, molecular biology, and systems biology), major questions have often been redefined and examined from new angles and with innovative tools. Analyses using such model systems as Drosophila, Xenopus, zebrafish, chick, human, and mouse have underscored the remarkable extent to which molecular and genetic pa- ways are conserved across species and throughout embryonic, fetal, and adult dev- opment. What we learn from the embryo, then, is not only of fundamental interest, but may well have future practical applications in the clinic. A number of excellent volumes, including several in this series (e. g. , Hema- poietic Stem Cell Protocols, Klug and Jordan, eds. , 2002), have surveyed methods used in the study of hematopoiesis-the processes by which the multiple lineages of the blood form from stem and progenitor cells during ontogeny and throughout the entire life of the animal. These collections of protocols have focused largely on the postnatal cells of mouse and human. Our understanding of hematopoietic devel- ment, however, has benefitted enormously from investigations in a variety of org- isms at different stages of ontogeny.