Plasma fractionation and blood transfusion are inherently linked. Blood bankers need to have a sincere interest in fractionation and purification techniques in order to understand the need for carefully controlled source material collection and initial processing. Developments point to a shift in technology, implementation and application of plasma fractions to be produced, such that early anticipation from both bloodbankers and fractionators in a joint interest and effort are needed. As usual there is good news and bad news. We are referring in that respect to the exciting presentation about the future of bloodbanking. Although the blood donor still plays a major role in bloodbanking, new technologies could terminate the conventional blood transfusion service in the next 20-40 years. Sooner or later DNA technology will play an important role in bloodbanking and bloodbankers will have to deal with cultivated red cells as a replacement of our donor blood. Several fractionation techniques like column chromatography, controlled pore glass chromatography, heparin double cold precipitation technology and polyelectrolite fractionation are available, which may result in better yields for some of the plasma proteins. These techniques are likely to replace in part the old Cohn fractionation in the near future.

This volume presents the proceedings of the Fourth Annual Symposium on the Molecular Biology of Hemopoiesis, held in Reno, Nevada, November 1 and 2, 1988. Its focus on erythropoiesis represents an attempt to cover a rapidly expanding field, which has gone from elegant studies of erythro poietin physiology, to molecular biology, to clinical applications and again to physiology. The rapid development has been made possible by cloning of erythropoietin gene and the availability of recombinant hormone. The regulation of heme and its derivatives has also been aided by techniques of molecular biology; there is now a concerted effort to better understand how these enzymes contribute to proliferation, differentiation and maturation of the erythron. Globin gene derrangements have been targets of recent research in an attempt to correct the defect by genetic engineering. In the chapters of this book, several groups "expressed" their views on this subject. Finally, we analyze various regulators of erythropoiesis, both in vivo and in vitro. Dr. Richard Levere was a pioneer in many studies of heme metabolism and of erythropoiesis. He has been a generous supporter of research in this field and of our past meetings. It is only. fitting that this volume should be dedicated to him."

The theme of this 14th International Symposium on Blood Transfusion is closely related to the work and scientific contributions of the Dutch cryobiology pioneer Dr. Herman W. Krijnen of the Dutch Red Cross Central Laboratory. Dr. Krijnen was known and respected in the national and interna tional blood transfusion community as an extremely competent scientist and a beloved and admired colleague. Dr. Krijnen was intentionally honoured with the invitation to open this symposium on cryopreservation and low temperature biology in blood transfusion and be the guest of honour at this event. Unfortunately, Dr. Krijnen suddenly died on the first of June 1989. In honour and mem ory of Dr. Krijnen this symposium will therefore be dedicated to him. Since the lOth International Symposium on Blood Transfusion in 1985 highlighted the theme of "Future developments in blood banking", major changes have occurred in the blood banking world. Most of these changes were forced upon the Blood Banks by the fear of spreading AIDS through contaminated donations. This not only led to the wide spread testing of blood, but also to a more appropriate counselling of the community and the blood donors in specific. Additionally, virus inacti vation techniques were introduced for those components derived from multiple donations and intended for a regular transfusion in haemophi lia patients and others.

The rapid and continuous upsurge of interesting data in the subject of tumor immunology necessitates the publication of an annual series to furnish the updated materials to the students, researchers, and clinicians in this rapidly advancing field. Concepts and methodologies are ever changing. Also, current research in tumor immunology promises to offer breakthroughs in the future. Important is the need to communicate to the right people the exact role of immunodiagnostic methods and immunolog ical intervention in cancer prevention and treatment. The role of immuno therapy in combination with conventional modalities of treatment needs in its proper perspective. Oncogene, interferon, lympho to be understood kines, monoclonal antibodies, natural killer cells, platelet-mediated cyto toxicity of antibody-coated target cells, suppressor cells, platelet-derived factors, plasma-blocking factors, control of suppressor cell function, ab rogation of plasma-blocking factors, etc., are some of the areas that are continually advancing. Progress in these areas will have implication in cancer therapy. Further, it is already understood that if immunocompe tence of the host can be maintained at a reasonably good level, there exists the potential to increase the therapeutic indexes of conventional modalities of treatment. This series will attempt to present updated infor mation in all these areas based on contributed and solicited articles. P. K."

Since 1952, postgraduate courses for practising physicians and speci alists have been given by the Medical Faculty of the University of Leiden in the Boerhaave Quarter, in which most of its clinics and laboratories are located. During these years, recent advances in a wide variety of m dical fields and subjects have been discussed by distin guished speakers from many countries. The steadily increasing atten dance has shown that, as could be expected from the rapid progress of modern medicine, there is a widely felt need for this form of postgra duate study. In 1957, therefore, the Leiden Medical Faculty appointed a permanent committee for the organization of postgraduate medical education. Of the courses given since then, certain material proved to have sufficient immediate scientific value to justify publication, and it now gives the Committee great pleasure to announce that in collaboration with the Leiden University Press it will publish the Boerhaave Series for Postgraduate Medical Education. The first volume of this new series is the product of the course on Human Blood Coagulation given in Novem ber 1968. It is our hope that this book will prove valuable not only to those who participated in the course but also to many others working in this and associated fields."

All medical specialists who must contend with the possibility of thrombosis will be interested in Anticoagulation. This book evaluates anticoagulation procedures from various points of view - from Current Trends in Anti-thrombotic Drugs, to Treatment of Ischemic Vascular Disorders; from Anticoagulants in Pregnancy, to Anticoagulation in the Elderly, from the Effects of Anticoagulant Therapy on the Heart, to Anticoagulation in various Surgical Procedures. Anticoagulation is a resource of approaches to the management of this common medical problem.

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."

Less than 50 years ago it was discovered that steady-state protein concentrations in plasma are the net result of continuous elimination and synthesis of protein molecules. The first quanti tative studies on the turnover and distribution of plasma pro teins were made around 1950, after the introduction of radio labeled protein preparations. Around 1970, another development in quantitative interpre tation of circulating proteins was initiated in clinical enzy mology. Estimation of cumulative release into plasma of cellular enzymes can be helpful in a variety of diseases to assess the extent of tissue damage and to evaluate therapy. Enzymes can be considered as biological tracers, i.e. minute quantities of protein can be accurately determined by their spe cific catalytic activities. However, radioactive tracers permit direct estimates of turnover and distr ibution by measurement of excreted radioactivity, possibilities that are not available for enzymes. Consequently, only a few techniques used in tracer studies with radiolabeled proteins can be applied to circulating tissue enzymes and this may explain the lack of communication between the fields of plasma protein metabolism and quantitative clinical enzymology. In the present study a summary is given of the basic methods used in both fields, with emphasis on the equivalence of various models and formalisms used by different authors. It is shown that major limitations in the study of circulating tissue enzymes can be overcome if two different, but simultaneously released, en zymes can be measured. The resulting method will also be applied to plasma protein metabolism."

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 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."

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 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.

AIMS OF THE COLOGNE-SYMPOSIUM ON RADIOLABELLED PLATELETS In 1976, M. Thakur et al (1) were the first to publish a paper concerning the in vivo thrombus detection with 111- In-labelled platelets. Previous attempts at scintigraphic thrombus localisation had been disappointing because of the unspecific binding of a number of the isotopes used, as well as the poor labelling efficiency or an insufficient low gamma-emitting property. Because of its physical characteristics (2.8 days half-life, 94% gamma emission) 111 Indium turned out to be the best isotope for platelet kinetic studies as well as for the measurement of platelet incorporation by Thrombi to be used up until now. The lipophile complexes of Ill-In (8-hydroxyquinoline, acetylacetone, tropolone) diffuse passively into the platelets without altering the function or the life span of the platelets. This advantage has let to an increase in the clinical applications of 1211-In labelled platelets. Today, radiolabelled platelets are used for thrombus detection in several different medical areas such as cardiology, nephrology. angiology or neurology. Even though many scientists and hospital doctors now routinely use radiolabelled platelet as a diagnostic tool, there is as yet not a standardized labelling method. In addition to this, there are neither standardized image procedures for the different clinical applications nor an agreement about specificity and sensitivity of the method. In 1983, a symposium on Radiolabelled Cellular Blood Elements was organized by M.Thakur, M.R.Hardeman and M.D.

During the past decade, there have been numerous direct and indirect scientific contributions to both the etiology and therapy of aplastic anemia and related bone marrow failure syndromes. Clinical observations, such as autologous bone marrow recovery after conditioning with immunosup pressive agents for bone marrow transplantation; failure to achieve en graftment in some identical twins without prior immunosuppressive ther apy; and hematologic response to immunosuppressive agents, have led to the concept of immune-mediated etiology of acquired aplastic anemia. Such a concept was further strengthened by laboratory findings, implicat ing the role of activated cytotoxic T lymphocytes and abnormal produc tion of inhibitory lymphokines. The immunologic mechanisms may also apply to the idiosyncratic bone marrow aplasias associated with drugs, toxic chemicals, and viruses. These agents may alter normal cellular recog nition sites by interacting with cellular components and result in loss of self tolerance. Immunologic mechanisms have long been advocated in many other organ failures, and the hemopoietic organ is no exception. It is of interest that parallel clinical and laboratory investigations in juvenile diabetes mellitus type I and in rodent models of this disease have yielded results compatible with the same pathogenic mechanisms. The infiltration of pancreatic islets by activated T lymphocytes, functional and morphological alterations of islet cells upon incubation with lymphokines such as gamma interferon and tumor necrosis factor, and clinical response to cyclosporine are a few examples."

An up-to-date overview of blood coagulation, hemostatis, and thrombosis, this volume also provides a state-of-the-art report of current anti-thrombotic and anti-coagulant strategies as well as a summary of current research interest in the area and potential future targets. It attempts to balance traditional pharmacology with the newer sciences of molecular biology and in so doing, sets a framework for future advances in the field. The book is a concise, current and useful reference for the basic researcher as well as the practicing physician working in the fields of cardiology, internal medicine or surgery.

This volume documents our growing understanding of the human major histocompatibility complex. The application of this information is ever more important as the limits of transplantation continue to be reduced, including the recent success of bone marrow transplantation between unrelated but closely matched individuals. In addition, the need to transfuse platelets in the face of immunologic barriers continues to challenge transfusion services. Thus, the serologic information summarized in this volume is essential for optimal patient care. At the same time, recombinant DNA technology has led to a revolution in our understanding of many aspects of basic biology. Among the advances has been the initial characterization of the structure of some HLA loci. While this will ultimately improve clinical services, constant reference to serologic data is essential so that the powerful new techniques can be applied in the most effective ways. The timing of the First Red Cross International Histocompatibility Workshop is fortunate as it brings together experts from around the world to address the state of the art. We are all grateful to Dr. John Lee and his colleagues for organizing the workshop, and for bringing together in this volume the material to be presented in Beijing during October 17-23, 1990. Leon W. Hoyer, M.D.

In 1628 William Harvey published his discovery of the existence of the microcirculation which he deduced from careful anatomical and physiological study. Thirty-three years later, Malpighi confirmed the presence of capillaries through direct microscopical observation. Subsequent scientific advance has been slow, and in view of the fact that microvascular in the genesis and expression of many pathophysiology may be implicated diseases, our know ledge of human microvascular function is surprisingly limited. This ignorance attests to the difficulty of studying something that is both minute and inaccessible without disturbing the quantity that is being measured. In the last fifteen years, however, direct techniques have been developed for studying human microvascular pressure, flow and permeability. These methods have provided new insights into human microvascular function in health and disease. At the same time there has been a steady growth of new indirect techniques based on a w ide range of physical principles that reflect some or other aspect of microvascular function.

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

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 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.

"The Blood Group Antigen FactsBook" has been an essential resource in the hematology, transfusion and immunogenetics fields since its first publication in the late 1990s.Thethird editionof "The Blood Group Antigen FactsBook" has been completely revised, updated and expanded to cover all 33 blood group systems. It blends scientific background and clinical applications and provides busy researchers and clinicians with at-a-glance information on over 330 blood group antigens, including history and information on terminology, expression, chromosomal assignment, carrier molecular description, functions, molecular bases of antigens and phenotypes, effect of enzymes/chemicals, clinical significance, disease associations and key references.
Includes over 330 entries on blood group antigens in individual factsheetsOffers a logical and concise catalogue structure for each antigen in an improved interior design for quick referenceWritten by 3 international experts from the field of immunohematology and transfusion medicine"

This unique publication explores diverse themes relating to thrombosis and embolism, from basic research at cell and molecular level to the actual care, prevention, and treatment of diverse categories of patients suffering from such diseases. Chapters cover a variety of topics including thrombosis and embolism in surgical patients, cancer patients, pregnant women and children and adolescents, as well as treatment of the conditions by traditional anticoagulants, novel oral anticoagulants, thrombolytic therapy, endovascular treatment and embolectomy. Readers may explore cutting edge research, recommendations from major societies, contemporary guidelines, areas of controversy and directions for ongoing and future research. The book features comprehensive information ranging from molecular mechanisms of diseases to the clinical features, diagnosis, and therapeutic regimens for treating a variety of clinical conditions. It has a broad appeal to scientists and research students as well as busy clinicians engaged in patient care, who will all find something important and useful amongst these carefully selected chapters.