Written by a team of world-leading experts in the field, who have published extensively

For primary care physicians, haematologists, surgeons and other healthcare professionals with an interest in thromboprophylaxis

Discusses both medical and surgical thromboprophylaxis and includes all relevant guidelines for thromboprophylaxis in pregnancy

Thoroughly revised and updated new edition

This second edition of the Handbook of Thromboprophylaxis expands upon the role of anticoagulants in clinical practice. In addition, it summarises key papers in the field and provides evidence-based guidelines for the use of anticoagulants in routine day-to-day practice.

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Between 1950 and 1960, remarkable advances were made in the develQpment Qf antihypertensive drugs, but since then, prQgress has been less rapid. This dQes nQt mean that no. new drugs have been intrQduced: Qn the cQntrary, their number has increased sharply; but since the advent Qf the beta-adrenergic blQckers no. new pharmacQdynamic principle has been discQvered that CQuid be applied widely as an antihypertensive. This has nQt been fQr want Qf effQrts, because many attempts have been made to. find new ways and means Qf influencing blQQd- pressure regulatiQn Qr the mechanisms invQlved in the pathQgenesis Qf hypertensiQn. HQwever, the results Qf these endeavQrs have mQstly been disapPQinting. Even thQugh high blQQd pressure can be treated mQre satisfactQrily tQday than many Qther diseases, the success achieved in cQmbating Qne Qf man's mQst frequent ailments shQuld nQt induce cQmplacency, but rather stimulate research tQwards further imprQvements. The present standstill affQrds an QPPQrtunity to. review the field Qf antihy- pertensive agents, fQr it is unlikely that fundamentally new drugs will appear in the near future. AlthQugh greater knQwledge has been gained Qf the mechanisms Qf blQQd-pressure regulatiQn and Qf the pathQgenesis Qf hypertensiQn, these ad- vances have had no. direct cQnsequences in the search fQr new therapeutics.

J.J. Van Loghem Previously to this symposium, five others have taken place in Groningen. The first one in 1976. This yearly scientific happening has continued. It has greatly stimulated the in terest in blood transfusion and all allied disciplines in our country. It is clear that these meetings are organized not only by a good scientist, but at the same time by a gifted or ganizer who, as director of the Red Cross Blood Bank Gro ningen-Drenthe, has shown that the heavy load of daily routine work can very well be combined with a large amount of experimental and clinical research in blood component therapy, coagulation disorders, blood group genetics and serology, the latter in cooperation with the Blood Group laboratory of the University Hospital Groningen under the directorship of Dr. Van Dijk. All these activities show how much a well-organized blood bank can contribute to a national blood transfusion orga nization."

Contents: Introduction and Overview Lymphopoietic Growth Factors: Pathophysiology of T-Cell Mediated Shock Induced by Bacterial Superantigens - Natural Killer Cells and Interleukin-2-Activated Killer Cells - TumourImmunogenicity Induced by Exogenous Interleukins - Cytokine Gene Therapy of Cancer - Analysis of T-Cell Receptor Variability in Tumour Infiltrating Lymphocytes - Clinical Studies with Interleukin-2: An Overview - Clinical Trials with Local Administration of Lymphopoietic Growth Factors - Clinical Trials with Interlaukin-2. The Rome Experience. Haematopoietic Growth Factors: Lymphohaematopoietic Growth Factor Use in Lung Cancer Patients - Clinical Trials with Haematopoietic Growth Factors and Peripheral Blood Stem Cells

Much of the attention presently paid to leukemia is the result of recent progress in understanding and treatment. Chemotherapy of leukemia started in the late 1940s, and combination therapy evolved in the late 1950s. It was at that time that the clonality of leukemia was realized, after the discovery of chromosomal and then biochemical and immunological markers. And now we have the new data on retroviral and cellular oncogenes and the reports on human T -cell lymphoma/ leukemia viruses. Many more steps forward could be enumerated in a field which is so rapidly making the hematological textbooks outdated. In this volume, thirteen in-depth reviews from large multicenter trials in the Federal Republic of Germany summarize the current state of diagnosis and management of leukemias. Childhood ALL and AML adult ALL and AUL were investigated. While cure appears to be achievable for more and more patients with acute leukemia, we still pursue the aim of optimal palliation in chronic leukemias. The management of patients with leukemia therefore varies to a large extent in aggressiveness of therapy. In some situations, rescue from an otherwise lethal disease is provided by bone marrow transplanta tion, which is discussed in two chapters."

Battle is a practical and sometimes lasting way of solving man's problems. It relies on the strength of the combatants and ignores the truth of the dispute. Discussion face to face can dissolve attitudes which have incorrectly determined judgements. The most striking example of this that I know is a Battle in Ireland in the eleventh century, where the king of Leinster fought a Viking prince. The Icelanders had raided Ireland for several generations in search of women, which they lacked since most of the population of Iceland were men who had arrived there by rowing long-boats from Norway. The prince was leading such a raid for the first time. Standing in the prow of the leading boat he saw Irish cavalry galloping along the beach to meet them. As they approached the shore the Irish king rode out of the band to challenge single combat. The Icelander jumped into the surf to meet him. As they raised their swords each realized that the other's face was like his own. When the Irish king spoke the other recognized the language. It had been spoken in Iceland by his grandmother who had been captured and taken there from Ireland. Swords were dropped and replaced by drinking horns. It was soon established that they were cousins. The battle gave way to a life-time of close co-operation.

An overview of diagnosis and current management of myelodysplastic syndromes.

- Reviews the performance of the pharmacological treatments currently available and analyses the potential for new treatments
- High quality clinical photos and figures to enhance descriptions and improve reader comprehension
- Useful reference text for healthcare professionals needing to know more about myelodysplastic syndromes

The 11 th meeting in "Modern Trends in Human Leukemia" took place from June 19 to 21, 1994 in Wilsede in the middle of the Liineburger Heide, South of Hamburg. Interwoven with the Leukemia program was the Nato-sponsored Symposium of the ASI-Series "Gene Technology in Analysis of Malignant and Inherited Human Diseases Related to Development" . The Wilsede meeting was continued on a ship of the Neva leading through lake Ladoga and lake Onega. The topics of both meetings included discussion on recent progress isolation and development of hematopoietic stem cells, genes crucial for development and diseases, methods of gene transfer, application of gene transfer; oncogenes and anti-oncogenes as targets for gene therapy; receptors and their ligands in normal development and diseases, immunology and immunotherapy, radiation biology, clinical leukemias and bone marrow transplantation. The Nato workshop concentrated not only on analysis of cell systems useful for somatic gene therapy, but also on actual themes directly related to correction of human diseases. The latter aspects emphasized themes related to biotechnology, the first part was by nature more general. We also included a few contributions that discussed perspectives for the future of gene therapy and possible relationships to evolution.

One of the most fascinating tools at the disposal of the molecular biologist is the medical clinic. The responsibilities of those who provide health care do not stop when they give optimal care to the individual patient and train their successors adequately. They also are under the obligation to obtain maximal information from every case they treat in order to reach a better understanding of the underlying illness in order to improve therapeutic results in the next patient. Fundamental research in pathological material is therefore a medical must as well as an opportunity for scientific work. The scientist working in this field can profit from nature's unasked for experiments, which are encountered by his medical colleagues in their clinical material. There are many examples of subjects of study - for instance hemoglobins and immunoglobulins - which started in a medical context and gradually developed into a field of prime interest for the molecular biologist. The study of blood coagulation is one of the younger areas of this kind.

This book has been written from two points of view: firstly, from the viewpoint of those who are involved in the diagnosis and treatment of lymphoid malignancies, who must meet the challenge of integrating the new biological insights into their knowledge of these diseases; and secondly, from the viewpoint of those who are involved in basic biological approaches to malignancy and immunology, who wish to know more about the function of the lymphoid tissues and their malignant diseases. Neoplasia of lymphocytes is a focus for considering many of the most important biological advances impinging on cancer in the past two or three decades, because malignant lymphoproliferative diseases offer unequalled opportunities for studying many aspects of cancer. We probably know more about lymphocytes than other normal cells because of the ease with which they can be obtained. For the same reason we probably know more about malignant lymphocytes. One or other aspect of most of the momentous advances in biology of the past two or three decades has implications for lymphoid malignancies: hybridoma technology and the use of monoclonal antibodies, gene technology, the understanding of oncogenes and growth factors in the control of growth and differentiation, insights into causation of cancer by potent tumour promoters such as the phorbol esters and by viruses, and knowledge of the control of growth function of lymphocytes themselves. Conversely, many of the advances in understanding lym phocytic leukaemias and lymphomas have implications for other cancers."

The translation of Blood Smears Reinterpreted was begun when the French original was still undergoing revisions. I was accorded the oppor tunity to question any statement or turn of phrase that was unclear to me or appeared liable to misinterpretation. It is my hope that as a result, ambiguities-particularly those inherent in differences between American and Eu ropean usage-have been removed and that I have at least ap proached the ultimate goal of any translation: to reflect the author's intention accurately while remaining as readable as the original. Beyond the role of translator, I was encouraged to assume the role of critic. As a result, some pages or even single sentences were hotly debated, sometimes for hours, as Marcel Bessis insisted that any inter pretations on which we could not agree should be so indicated. In fact our discussion invariably ended in agreement, though they led to changes of a sentence here or a word there and, on occasion, to the addition of a footnote or a brief paragraph.

The 6th volume of the book series Acute Leukemias presents both therapeutic and prognostic updates of the most recent results of major multicenter clinical trials. Additional chapters report on new trends in leucemia cell biology, the monitoring of minimal residual disease and secondary leucemias as well as new antileucemic drugs, antimicrobial strategies and the use of cytocines. Acute Leukemias VI provides a new update on the rapid progress being made internationally concerning leucemic diseases.

The European School of Oncology came into existence to respond to a need for informa tion, education and training in the field of the diagnosis and treatment of cancer. There are two main reasons why such an initiative was considered necessary. Firstly, the teaching of oncology requires a rigorously multidisciplinary approach which is difficult for the Universi ties to put into practice since their system is mainly disciplinary orientated. Secondly, the rate of technological development that impinges on the diagnosis and treatment of cancer has been so rapid that it is not an easy task for medical faculties to adapt their curricula flexibly. With its residential courses for organ pathologies and the seminars on new techniques (laser, monoclonal antibodies, imaging techniques etc.) or on the principal therapeutic controversies (conservative or mutilating surgery, primary or adjuvant chemotherapy, radiotherapy alone or integrated), it is the ambition of the European School of Oncology to fill a cultural and scientific gap and, thereby, create a bridge between the University and Industry and between these two and daily medical practice.

United States government. Defense Nuclear firms, Hoffman-LaRoche and Ciba-Geigy, and by Agency, Armed Forces Radiobiology Research In- the American firm, Travenol. stitute. SIEGMUNDJ. BAUM Furthermore, we greatly appreciate the gener- G. DAVID LEDNEY ous financial support by the Swiss pharmaceutical vi Xlll List of Contributors Part I Regulation of Stem Cell Proliferation L. G. Lajtha 1 Regulation of Stem Cell Proliferation 3 L. G. Lajtha and E. G. Wright Introduction 3 Experimental Evidence 3 Summary 7 References 7 Contents 2 Surface Antigens of Hemopoietic Stem Cells: The Expression of BAS, Thy-1, and H-2 Antigens on CFU-s 9 Ger van den Engh, Jim Russell, and Diane de Cicco Introduction 9 Materials and Methods 10 Results 11 Discussion 13 Summary 14 Acknowledgments 14 References 15 3 The Regulation of Hemopoiesis: Effect of Thymosin or Thymocytes in a Diffusion Chamber 17 S. J. Sharkis, A. Ahmed, L. L. Sensenbrenner, W. W. Jedrzejczak, A. L. Goldstein, and K. W. Sell Introduction 17 Materials and Methods 17 Results 18 Discussion 20 Summary 21 Acknowledgments 21 References 21 4 Anti-CFU-s Activity of Rabbit Anti- mouse Brain Serum: Mechanism of Action 23 Solomon S. Adler, Richard D. Kuznetsky, and Frank E. Trobaugh, Jr. Introduction 23 Materials and Methods 23 Results 26 Discussion 29 Summary 31 Acknowledgments 31 References 31 vii Contents Part II Ralph van Furth, Theo J. L. M. Goud, and Physiology of Committed Dick van Waarde Stem Cells 33 Introduction 65 D.

Knowledge of mechanisms involved in the pathogenesis of occlusive arterial dis eases is fundamental for the design of prevention and treatment. A series of studies based on in vitro investigations, the experimental animal and the human being have slowly increased our understanding of cardiovascular diseases and unveiled their secrets to us. Over the last 60 years it has been generally assumed that dietary fats and lipids and the occurrence of atherosclerosis are closely related. Yet, even if epidemiological studies clearly indicate the existence of an association between the amount of composition of dietary lipids and morbidity and mortality of cardio vascular disease, our basic knowledge on cause and effect is still hidden in a cloud of uncertainty. The present book discusses the relation between dietary lipids and arterial throm bosis, which latter process has been observed in the coronary arteries in up to 90% of subjects with acute myocardial infaction. In this volume Dr. Hornstra, who has occupied himself with thrombosis research with never-failing enthusiasm, great skill and critical approach for the last fifteen years, tries to establish possible links between lipid metabolism and thrombosis. His literature studies are comprehensive and his investigations are impressive in that they give a new dimension and a new methodology to research of lipids and thrombosis."

xi List of first authors xiii Acknowledgements xv INTRODUCTICN Approaches to radiolabelling blood d-c cells: past, present and future M. L. Thakur 3 CELL LABELLllJG TEDlNIQUES 2 Labelling techniques of granulocytes and platelets 17 with 111 In-oxinate M. R. Hardeman, E. G. J. Eitjes-van Overbeek, A. J. M. van Velzen, M. H. Rovekarnp 111rndium-labelling of human washed platelets; kinetics 3 29 and in vivo sequestration sites M. Eber, J. P. Cazenave, J. C. Grob, J. Abecassis, G. !o1ethlin 111Indium loss from platelets by in vitro and ex 4 44 vivo manipulation R. J. Hawker, C. E. Hall, H. C-oldman, C. N. McCollum PIATELEl'S: KrnETIC STUDIES 5 The maturation of megakaryocytes and their precursors 65 J. H. Paulus 6 !o1egakaryocytic precursors 74 J. Breton-Gorius, W. Vainchenker 7 !-1ethods of quantification of platelet production 86 in man. A critical analysis Y. Najean vi 8 Platelet production rate deteDmination with (75se)_ seleno-m:thionine R. Cardinaud, E. Dassin 96 9 Platelet kinetics: the state of the art A. duP Heyns 110 10 Platelet kinetics A. M. Peters 130 Evaluation of models to deteDmine platelet life 11 span and survival curve shape M. G. LOtter, C. P. Herbst, P. N. Badenhorst, A. duP Heyns, P. Wessels, P. C. Minnaar 139 12 Canparison of three m:thods evaluating platelet survival tim: in patients with prosthetic heart valve J. Schbath, D. Ville, B. Hathy, B. Sanchini, E. Benveniste, J. Belleville, M. Dechavanne, J. P. Boissel, J.

The practice of transfusing blood started at the bedside but over the last few decades blood transfusion has become more and more a laboratory directed discipline. The emphasis on serology and laboratory controlled measures has made blood transfusion safer and more effective, but laboratory and clinical aspects of the discipline have tended to become increasingly separated. As a result of this separation clinical developments in blood transfusion may not have derived full benefit from the knowledge accrued in blood transfusion services. Over the last five years the Red Cross Blood Bank Groningen-Drenthe has organised yearly symposia with a clinical theme in order to bring blood banks and clinicians closer together. Many of the recent major advances in clinical medicine have been based on developments in blood transfusion practice. This is certainly true for paediatric medicine. For instance, in paediatric oncology, including leukemia, cell separator programmes have made available new forms of support. Further, blood component therapy has provided an effective means of control in some of the bleeding disorders of children. Some of these topics are discussed in this symposium dealing with intensive care. Haemolytic disease of the newborn and exchange transfusion are other aspec.ts of intensive care. Our purpose in dealing with them was twofold.

G. F. FUEGER Among the many processes in Physiology few appear mo e inviting to be studied by tracers and external imaging than the variety of the routes of migratory (blood) cells in health and disease. Much emphasis has been placed lately on the methods of labelling of the white blood cells. It is obviously quite important and necessary to refine the methods of leucocytic labelling, particularly to search for ways to label selectively a specific group of white blood cells, but there is also the need to review and keep abreast with the developing knowledge of the white blood cells themselves, especially their behaviour under pathological conditions, as seen by histology and scintigraphy, their biological properties, their immunological characteristics and the mechanisms of the control of leucocytic functions. Similarly, it appears desirable to analyze animal models of inflammation as well as to review the dosimetry and the biodistribution of labelled white blood cells in humans. This book is the result of a cooperative effort to review certain highlights of the physiology of leucocytes, labelled and unlabelled, as a corollary to the effort concerning the labelling of white blood cells. In preparing this book we aim for a better understanding and definition of the goals to be achieved by the successful labelling of the migratory cells of the body. XI CONTRIBUTORS Becker, H. Medizinische Universitaetsklinik der Uni versitaet Graz, Graz, Landeskrankenhaus, haus, Austria Bjurman, B. Department of Radiation Physics, General Hospital, Malmoe, Sweden Chiles, C."

As a clinical discipline blood transfusion encompasses enormous vista, vary ing from biotechnology to molecular biology, from plasma products, cell biology and growth factors to interleukines. Growth of knowledge in this field has been rapid, and expertise is now required to be mastered and renewed in translating these ideas for patient care. Various types of cells could be harvested - progenitor stem cells derived from bone marrow or from circulating blood as a source for transplants; in the hemostatic armoury platelets could be used prophylactically; granulocytes and mononuclear cells are available for treatment of infections or immune modulations. However, their therapeutic use carries potential complications including graft versus host disease and CMV-infection. Prevention of such complications by irradiation and by removal of immunocompetent leukocytes are important issues. Thus, production of such therapeutic materials ought to address the issues at the earliest, to eliminate those problems while adhering to the con cept of high quality; the impact of storing platelets for longer periods by using improved plastic containers or storing almost indefinitely in frozen state should be explored. Rapid progress in cell culture techniques and bio technology have enriched the transfusion medicine armoury with lympho kines, interferons and cell colony growth factors which have great potentials for enhancement of basic knowledge as well as considerable therapeutic applications in patients.

Proceedings of the Eighth Annual Symposium on Blood Transfusion, Groningen 1983, organized by the Red Cross Blood Bank Groningen-Drenthe

Hairy cell Leukaemia (HCL) has always attracted an interest out of all proportion to its frequency and continues to do so. There are two reasons for this. The first is that the disease is unusually responsive to therapy and second is that it has provided a number of important insights into B-cell biology. This monograph is a comprehensive account of hairy cell leukaemia and aims to provide a more detailed account than is available in the existing literature. The work is timely because a consensus has now emerged concerning accurate differential diagnosis a nd curative treatment. These aspects therefore form the focus of the book and are considered in detail. The basic advances in the laboratory that encourage the belief that elucidation of the underlying oncogenic event in the disease may be within reach. The background to this belief is extensively renewed. As a result the monograph will be of interest and practical value to both clinicians and researchers in this and related fields.

Human Lymphoma: The Clinical Implications of the REAL Classification is a unique volume. It is based on the recent developments in classification and overall understanding of human lymphoid neoplasms which are relatively common neoplasms and which epidemiological evidence suggests are increasing in frequency. This field has been the cause of confusion in the past as a result of conficting ideas on the classification of lymphoma and related diseases. However a new vision of the field has emerged and the is encapsulated in the pioneering REAL classification and in a forthcoming WHO scheme, both of which are covered in the book. The volume will appeal to hematologists, pathologists and oncologists and will, thanks to a diverse and expert authorship, serve to increase the working knowledge of all three groups.

Bone marrow transplantation has emerged as a major form of treatment for a broad range of human diseases. Marrow transplantation has many unique biologic features and its principles differ markedly from the transplantation of solid organs. This volume overviews the present status of bone marrow transplantation and summarizes recent progress and controversies. Ad vances in defining the underlying biology of marrow transplantation are discussed. The current status of several major clinical problem areas are reviewed, including engraftment, acute and chronic graft-versus-host dis ease, immunodeficiency, and opportunistic infections. The therapeutic role of allogeneic and autologous bone marrow transplantation is discussed, and results are compared with alternative therapies. lX List of contributors ANASETII, CLAUDIO, M. D. , Fred Hutchinson Cancer Research Center, 1124 Columbia Street, Seattle, Washington 98104 APPELBAUM, FRED, M. D. , Fred Hutchinson Cancer Research Center, 1124 Columbia Street, Seattle, Washington 98104 ARMITAGE, JAMES 0. , M. D. , Department of Internal Medicine, Univer sity of Nebraska Medical Center, 42nd and Dewey Avenue, Omaha, Nebraska 68105 BEATIY, PATRICK G. , M. D. , Fred Hutchinson Cancer Research Center, 1124 Columbia Street, Seattle, Washington 98104 BIERMAN, PHILIP J. , M. D. , Department of Internal Medicine, Univer sity of Nebraska Medical Center, 42nd and Dewey Avenue, Omaha, Nebraska 68105 BUTTURINI, ANNA, M. D. , Department of Pediatrics, University of Parma School of Medicine, Parma, Italy CHAMPLIN, RICHARD, M. D.

Where do you begin to look for a recent, authoritative article on the diagnosis or management of a particular malignancy? The few general oncology text books are generally out of date. Single papers in specialized journals are informative but seldom comprehensive; these are more often preliminary reports on a very limited number of patients. Certain general journals frequently publish good in-depth reviews of cancer topics, and published symposium lectures are often the best overviews available. Unfortunately, these reviews and supplements appear sporadically, and the reader can never be sure when a topic of special interest will be covered. Cancer Treatment and Research is a series of authoritative volumes that aim to meet this need. It is an attempt to establish a critical mass of oncology literature covering virtually all oncology topics, revised frequently to keep the coverage up to date, and easily available on a single library shelf or by a single personal subscription. We have approached the problem in the following fashion: first, by dividing the oncology literature into specific subdivisions such as lung cancer, geni tourinary cancer, pediatric oncology, etc.; and second, by asking eminent authorities in each of these areas to edit a volume on the specific topic on an annual or biannual basis. Each topic and tumor type is covered in a volume appearing frequently and predictably, discussing current diagnosis, staging, markers, all forms of treatment modalities, basic biology, and more."

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.