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.

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."

A comprehensive collection of classic and innovative methodologies used in many laboratories for the investigation of multiple myeloma. These readily reproducible techniques range from the standard Plasma Cell Labeling Index methodology to a final chapter on making sense of microarrays, and include the full spectrum of cytogenetic and molecular diagnostic methods. The protocols follow the successful Methods in Molecular Medicine (TM) series format, each offering step-by-step laboratory instructions, an introduction outlining the principle behind the technique, lists of the necessary equipment and reagents, and tips on troubleshooting and avoiding known pitfalls. These proven techniques are ideal for studying the pathogenesis of multiple myeloma and identifying new therapeutic targets.

12 The average human body has in 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.

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.

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.

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.

Cytokines are cellular growth factors which also provide communication between cells and their milieu. This clearly is an exciting area in modern medicine that will have significant impact on various facets of transfusion. Erythropoietin therapy stimulates red cell production while thrombopoietin seems to positively affect megakaryopoiesis and can be an added armamentarium for the thrombocytopenic patient. Using haematnopoietic growth factors, stem cells could be mobilized early to the peripheral blood for collection and subsequent transplantation into haemato-oncology patients instead of bone marrow transplantation. Using a cocktail of cytokines in cell culture, stem cells could be expanded and selected for therapy. Cytokines and growth factors can even be modified, which may lead to successful gene therapy in malignancies, including solid tumour vaccines. However, the presence of cytokines in certain blood products could have biological effects following transfusion, although its clinical relevance needs to be ascertained. There is much potential for the use of cytokines in the treatment of infections. Early diagnostic methods are now available to monitor their levels and relevance. It is likely that cytokines will increasingly play a role in therapy and could develop our fundamental knowledge about the development of T-cells. An ethical dilemma remains, however, regarding the use of cytokines in healthy donors for harvesting suitable specific cells. Longer clinical observation will be necessary to gather the necessary information. Cytokines and growth factors in blood transfusion was the theme of the 21st International Symposium in Blood Transfusion, where twenty clinicians and scientists, experts in their own fields, were invited to update the above information. Their findings are presented in four sections in this volume: Fundamental aspects - cytokines in development of T-cells, growth factors in haematopoiesis, growth factor receptors and signal transduction, cytokine response in platelet and whole blood transfusions. Function, production and diagnosis &endash; laboratory diagnostics of cytokines and growth factors, cytokines in blood components, cytokines and growth factors in cell expansions, cytokines for genetic modification towards gene therapy, progenitor cells from healthy donors. Application in clinical medicine &endash; clinical relevance of cytokines in transfusion products, cytokines and growth factors in solid tumours, gene therapy in malignancies, vaccine strategies inducing T-cell immunity against tumours, cytokines in the treatment of infections, thrombopoietin and megakaryopoiesis. Future potential use in transfusion medicine &endash; erythropoietin, immunotherapy, ethical aspects of the use of cytokines and growth factors in donors, potential of cytokines and growth factors in transfusion medicine.

Building on the considerable expertise of the dysproteinemia unit at Mayo Clinic, this book spans the gamut from multiple myeloma, the most frequent and most serious of the monoclonal gammopathies, to the rarest related disorders. Laboratory evaluation, associations with nonhematologic disorders, monoclonal gammopathies of undetermined significance, the more obscure plasma cell dyscrasias, amyloidosis, other immunoglobulin deposition disorders, Waldenstrom macroglobulinemia, and Fanconi anemia are among the topics covered. Naturally, particular attention is paid to multiple myeloma: history, pathogenesis, clinical and laboratory diagnosis, modern therapy, and prognosis. Subsets of multiple myeloma such as solitary plasmacytoma, extramedullary plasmacytoma, and plasma cell leukemia are reviewed. This volume is designed to serve as a long-lasting reference for clinicians and scientists involved in the management of multiple myeloma and associated disorders."

Mr. Chairman, ladies and gentlemen, with great pleasure I like to welcome you in the cityofGroningen and hope that you will have an enriching and enlighten ing discussion on the conference theme on risk management in blood trans fusion. The organisation of this symposium aims at scientific networking by discussing in an international forum the most important themes of current interest in relation to the state of the art in transfusion medicine. Dr. Cees Smit Sibinga took the initiative in 1976 to start organising the blood bank symposia as they were named in the beginning. Without doubt these symposia have contributed considerably to the development of transfusion medicine. To illustrate the fact that these symposia came to my attention I recollect that I have attended the symposium in 1978, chaired by Dr. Leo Vroman, in my capacity in those days of alderman deputy mayor of the city. So, it has been a long time since. After having been away from Groningen for 18 years I have been inaugurated last week as a mayor and it is a plcasure to be again in your midst. The scries of annual symposia on blood transfusion have contributed to mark the city of Groningen on the map of the international scientific world. A great number of prestigious institutes all over the world involved in the development of transfusion medicine have linked to Groningen and we are proud of that."

The first book to cover both basic science and clinical research, providing a comprehensive review of the current knowledge on cytokines and cancer. Written by leading figures in the field of cytokine biology and cytokine therapeutics.

Edited by two leading orthopedic surgeons who are specialists in the treatment of hemophilia, Orthopedic Surgery in Patients with Hemophilia shows all the surgical techniques needed for surgical treatment of musculoskeletal complications of hemophilia. A practical guide, designed for use on the ward or in the office, this book draws on the experience of numerous specialists worldwide, from developed and developing countries. As well as orthopedic surgery, it also covers research, hematology, and rehabilitation. Although of primary interest to the orthopedic surgeon, rheumatologist, and physiotherapist, this book will also be relevant to the hematologist responsible for the care of the hemophiliac patient.

Active specific immunotherapy is a promising but investigational modality in the management of cancer patients. Currently, several different cancer vaccine formulations such as peptides, proteins, antigen-pulsed dendritic cells, whole tumor cells, etc. in combination with various adjuvants and carriers are being evaluated in clinical trials (1-3). To determine the optimal cancer vaccine strategy, a surrogate immunological end-point that correlates with clinical outcome needs to be defined, since it would facilitate the rapid comparison of these various formulations. Traditional immunological assays such as ELISA, proliferation and cytotoxicity assays can detect immune responses in vaccinated patients but are not quantitative. In contrast, novel assays such as enzyme-linked immunospot (ELISPOT) assay, intracellular cytokine assay and tetramer assay can quantitate the frequency of antigen-specific T cells. Of these, the ELISPOT assay has the 5 lowest detection limit with 1/10 peripheral blood mononuclear cells (PBMC) and has been determined to be one of the most useful assays to evaluate immune response to cancer vaccines (4). However, the IFN-? ELISPOT assay is not an exclusive measure of cytotoxic T-lymphocyte (CTL) activity as non-cytotoxic cells can also secrete IFN-?. Additionally, CTL with lytic activity do not always secrete IFN-? (5). A more relevant approach to assess functional activity of cytotoxic lymphocytes would be to measure the secretion of molecules that are associated with lytic activity. One of the major mechanisms of cell-mediated cytotoxicity involves exocytosis of cytoplasmic granules from the effector toward the target cell.

In general, several mathematical models can be designed in order to describe a biological or medical process and there is no unique criterion which model gives the best description. This book presents several of these models and shows applications of them to different biological and medical problems. The book shows that operations research expertise is necessary in respect to modeling, analysis and optimization of biosystems.

What we now call 'deep venous thrombosis' (DVT) has been elucidated by a diversity of investigative approaches during the past four centuries. The authors of this book survey the history of the field and ask: why has one of these perspectives - the haematological/biochemical - come to dominate research into the causation of DVT during the past 50 years and to exclude alternatives? In answering this question, the authors show that the current consensus model is conceptually flawed.

Chronic lymphocytic leukaemia (CLL) is the most common leukaemia in the Western world. It is also the prototype of B-cell chronic lymphoid malignancies and of their ramifications within the fields of hematology, immunology and oncology. For a long time the Cinderella of lymphoid malignancies CLL has now become the focus of major interest and an increasing number of investigators from different areas, including genetics, molecular biology, basic and applied immunology are becoming actively engaged in the investigation of CLL. Clinicians are considering CLL as a very interesting target of many projects which aim at translating the new and exciting developments of basic science into effective new approaches to the patient.

MSC (mesenchymal stem cells) have been reported to initiate revascularization after injury, to facilitate engraftment of blood-forming stem cells, and to reduce the incidence of graft-vs. host disease through their immune-suppressive qualities. Finally, bone marrow-derived MSC have been reported to home to areas of solid tumor revascularization, and thus may be used as delivery vehicles to target ablative agents into dividing tumor cells. Recently the characteristics of human MSC from adipose (fat) tissue have also been identified. The possibility of repairing tissues, speeding stem cell engraftment, and targeting solid tumors for specific killing, using MSC easily harvested from bone marrow, or better yet, from unwanted fat tissue, holds broad appeal, and is an intriguing possibility that could have dramatic effect on health care.

This book has information on how to isolate, grow, and characterize MSC from marrow and fat, and gives important insight into how these cells may be used for gene delivery and cellular therapies in the future. Updates on emerging clinical trials are given.

High levels of homocysteine, a sulfur-containing amino acid derived from methionine, have recently been identified as a very important risk factor in cardiovascular disease. Homocysteine abnormalities are also thought to contribute to birth defects and dementia. There are many common genetic disorders and problems (such as vitamin deficiency) that adversely affect the metabolism of homocysteine. In this book a team of the world's experts in the field provide a clear, current, clinical analysis of the biochemistry, genetics, and epidemiology of homocysteine disorders, providing a uniquely comprehensive account of the broad range of medical, nutritional and methodological implications of homocysteine for health and disease.

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.

This is a comprehensive textbook of Hodgkin's and non-Hodgkin's lymphomas written by leaders in the field of childhood lymphomas. It includes clinical, pathologic and molecular biology of each subtype of lymphoma. The pathology chapters are comprehensive and include excellent photographs. The book is at the level of subspecialists in pediatric hematology and oncology, radiation oncology, pediatric surgery and hematopathology.

Now more than ever, thrombotic and thromboembolic disorders as well as related diseases such as malignancies, arteriosclerosis, diabetes mellitus, hypertension, and obesity are the leading causes of morbidity and mortality. They have become urgent medical problems with serious economic consequences in industrialized and devel- ing countries alike. At the same time, the impact of molecular biology and genetics on our understanding of thrombosis and hemostasis is rapidly growing stronger as well as our knowledge of regeneration and development of specific tissues, organs, and embryos. Researchers are also constantly learning more about cardiovascular diseases as well as regulatory mechanisms for various intrinsic and extrinsic stimuli in viable tissues. In this volume, our intention has been to present the latest relevant information in molecular biology and genetics as well as the clinical implications of a better understanding of pathophysiology, novel diagnostic methodologies, and therapeutic applications for new methods of prevention in thrombosis/hemostasis and related disorders, including atherosclerosis. The dramatic advances in knowledge of thrombosis/hemostasis and vascular biology since the first publication of Recent Advances in Thrombosis and Fibrinolysis, edited with Japanese colleagues, in 1991, have required extensive revision in order to highlight and review recent progress in the field. The editors also gratefully welcome the seven distinguished non Japanese authors, who, with their valuable contributions on subjects beyond the coverage by Japanese authors, have made this new edition truly international.

Integrative medicine strives to incorporate the best of complementary and conventional modalities. This book details integrative oncology, a nascent field building a rigorous evidenced-based clinical medicine, research, and educational foundation. It examines five prestigious, comprehensive cancer centers based in the US, covering how these centers started their programs, what they are currently doing, and recommendations for starting integrative medicine clinics. The book also discusses the potential harm of alternative and complementary medicine, legal issues, and how to communicate with patients.

Developed by the Blood and Marrow Transplant team at Oregon Health & Science University Knight Cancer Institute, this pocket guide provides management guidelines for hematopoietic stem cell transplant patients from the moment of their initial consultation throughout the transplant process. It includes indications for transplant, essential details for patient/donor evaluation, recommendations for management of complications during and after transplant, and guidelines for long-term follow up as well as step-by-step instructions for common procedures and documentation guidelines.

An essential tool for providers, this guide presents a multidisciplinary approach to information you will need to provide quality care for your patients.

The aquaporin field has matured at an exceptionally fast pace and we are at the verge to develop serious strategies to therapeutically modulate aquaporin function directly or via regulatory networks. Key prerequisites are available today: i. a considerable (and growing) number of aquaporin crystal structures for the rational design of inhibitory molecules, ii. elaborate molecular dynamics simulation techniques for theoretical analyses of selectivity mechanisms and docking experiments, iii. comprehensive data on aquaporin immunohistochemistry, iv. aquaporin knockout animals for physiological studies, and v. assay systems for compound library screenings. The structure of this volume on aquaporins follows the points laid out above and thus covers the developments from basic research to potential pharmacological use. Situated between pharmacology textbooks and recent scientific papers this book provides a timely overview for readers from the fundamental as well as the applied disciplines.