This title includes proceedings of the first European Symposium on platelet immunology held in Paris, Palais du Luxembourg (France), 1 to 2 March 1990.

Hemostasis and Thrombosis , Sixth Edition Since publication of the First Edition in 1982, Hemostasis and Thrombosis has established itself as the pre-eminent book in the field of coagulation disorders. No other book is as inclusive in scope, with coverage of the field from the standpoint of both basic scientists and clinicians. This comprehensive resource details the essentials of bleeding and thrombotic disorders and the management of patients with these and related problems, and delivers the most up-to-date information on normal biochemistry and function of platelets or endothelial cells, as well as in-depth discussions of the pharmacology of anticoagulant, fibrinolytic, and hemostatic drugs. NEW to the Sixth Edition... * A new team of editors , each a leader in his field, assures you of fresh, authoritative perspectives. * Full color throughout * A companion website that offers full text online and an image bank. * A new introductory section of chapters on basic sciences as related to the field * Entirely new section on Hemostatic and Thrombotic Disorders Associated with Systemic Conditions includes material on pediatric patients, women's health issues, cancer, sickle cell disease, and other groups. * Overview chapters preceding each section address broad topics of general importance.

Text in French.

A Guide to Paediatric Red Blood Cell Disorders is a comprehensive text on common red blood cell disorders encountered in children. It is a useful guide to postgraduate doctors training in paediatrics and haematology, medical undergraduates, primary care physicians and practising clinicians. The book is divided into five sections. The first section provides a detailed understanding of the basic concepts and approach to red blood cell disorders in children. This section includes information on the structure and function of red blood cells and haemoglobin, epidemiology and aetiology of anaemia and clinical and laboratory evaluation of childhood anaemia. The next three sections will provide information on paediatric conditions that result in microcytic, normocytic and macrocytic anaemia, respectively. The final section will be on conditions leading to polycythaemia in neonates and children. Throughout the book, the emphasis is given to common conditions that are frequently encountered in clinical practice. However, rare but clinically important conditions have also been included. Each chapter is divided into subheadings to describe the epidemiology, aetiology, genetic basis, molecular pathology, pathophysiology, classification, clinical features, investigations, diagnosis, treatment, follow-up and prognosis of each disorder. At the end of each chapter, a section on recent advances provides information on promising novel developments and experimental approaches for treating these diseases. This book will help medical undergraduates to grasp concepts and understand the entire spectrum of red blood cell disorders in children. For practising clinicians, this will be a useful guide on how to approach a child with anaemia, which is one of the most common presentations to general practice, field clinics and hospitals. For postgraduate doctors training in paediatrics and haematology, the book will provide comprehensive information on how to manage common as well as complex red blood cell disorders in children. This book is concise, reader-friendly and written in simple English, which can be understood by non-native speakers. It will aid readers across the globe to grasp the concepts of paediatric red blood cell disorders easily and be knowledgeable and up to date in managing these patients.

Hematology is often considered a challenging subject by students and junior medical staff alike. Using key scientific and clinical principles, this succinct guide provides a summary of modern day-to-day clinical practice in paediatric hematology. Focusing on the facts that underpin patient management, each chapter offers an initial summary of a particular paediatric hematologic condition. Several key clinical scenarios set out how common difficulties should be managed, from the neonate with line thrombosis, to the newly presenting patient with leukaemia, and the child who has suffered a stroke. Covering all hematology topics on the syllabus of the American Board of Paediatrics subspecialty examinations, this authoritative guide is ideal for both postgraduates and junior doctors, whose understanding of hematological conditions will increase greatly upon reading. This comprehensive and practical book specifically aims to equip clinicians to diagnose and manage children with hematological illness, and to support them and their families.

Intricate processes involved in perpetuating the multitude of physiological phenomena in the human body often encounter aberrations and omissions in the genetic code of life. While such errors often lead to lethal diseases, at other times they provide distinctive survival advantages and thus unscramble cues to unconventional therapeutic strategies for life-threatening conditions. Hereditary Persistence of Fetal Hemoglobin (HPFH) is one such condition wherein the typically inactivated fetal form of hemoglobin (HbF) remains overexpressed even in adult stages of the bearer's life. Strikingly, this condition is known to ameliorate pathological manifestations in patients with aberrant adult hemoglobin synthesis (e.g. I(2)-hemoglobinopathies like I(2)-thalassemia, sickle cell disease etc.). Early researchers in the field expected such patients to suffer from clinical challenges owing to HbF's high affinity to oxygen and consequent difficulty in its release to cells and tissues. Surprisingly, these patients are known to lead a physiologically normal life. Modern-day hematologists and clinical researchers have looked-up to the concept of "HbF reactivation" as a potential curative strategy for patients suffering from I(2)-hemoglobinopathies like I(2)-thalassemia and sickle cell disease. As a result, several drugs like hydroxyurea, 5-azacytidine, cytosine arabinoside, natural products etc. have been tried in clinics to elevate HbF levels in such patients with limited success and poor understanding on the mechanisms of their action. Associated side-effects and complications of using cytotoxic agents like these restrict their use in most instances. Fortunately, with the advent of newer molecular tools and techniques, researchers are focusing their attention to reengineer the molecular machinery and thus reactivate the gamma-globin gene. This book brings together a selection of chapters dedicated to fetal hemoglobin a its physiological role, regulation, methodologies to manipulate and future strategies. Researchers and scientists interested in the topic will have a comprehensive understanding of the current concepts on fetal hemoglobin modulation and therefore will serve as a launching pad for their research ideas.

The authors summarise advances in human pluripotent stem cells-derived erythroid development and molecular regulatory mechanisms. This research may provide a new perspective on human embryo erythropoiesis and a possible treatment for some hematological diseases. Erythrocytes are well equipped to carry out their functions due to a dynamic cell membrane, their inherent shape and lack of organelles and cytoplasmic viscosity. As such, the following section focusses on the causes of these modifications and their clinical implications. As an example of complexity in research towards the development of erythrocyte membrane-based drug delivery systems starting from animal erythrocyte, morphological, biochemical and drug release profiles will be reviewed in the penultimate chapter. The final chapter investigates the electrochemical behavior of erythrocytes at platinum, carbonaceous, and optically transparent electrodes via polarization and coulometric measurements. The order of magnitude of the quantity of electrons transferred between erythrocytes and electrodes was determined, and potential ranges showing indifference of the electrode toward red blood cells were identified.

Prevailing physiological concepts (PPC) of blood circulation consider the cardiovascular system (CVS) an autonomous system that has its own goal and mechanisms for achieving it. Physiologists agreed that complex neural and humoral controllers of a mean arterial pressure (MAP) indirectly alter the blood flows for satisfying cellular needs. However, PPCs are incapable of explaining the causes of long-term shifts of an MAPs rest level. In particular, this affects current understanding and cure technologies of arterial hypertension (AH). Considering AH as a disease, physicians seek a cure that effectively decreases the elevated pressure. This gave rise to the palliative cure softening of AH symptoms without an understanding of AHs primary causes. But this strategy, working until the patient intakes antihypertensive drugs, often leads to AHs further development, and in extreme cases current antihypertensive drugs are helpless. These limitations of PPC are forced to seek a circulations extended physiological theory (EPT), explaining the mechanisms of both normal and altered MAPs. In the EPT presented in the book, CVS is considered a constituent part of a more complex functional super-system (FSS) that appeared in a multi-cellular animal organism during the co-evolution of specialized cells. The general goal of the FSS is to provide optimal physiochemical and energy states of the cell cytoplasm. To achieve this goal under a stochastic total and local variations of cells activity, FSS should control: i) The cardiac output; ii) the regional and local blood flows; and iii) the chemical composition of both arterial and venous blood. Under chronic energy shortage, FSS should also provide an adequate increasing of ATP-synthesis in mitochondria of stagnated cells. So, under the ineffectiveness of current mitochondria, FSS must enrich the arterial blood by chemicals providing the biogenesis of mitochondria. However, neither the energy providers nor the providers of blood chemistry are properly involved in PC of the blood circulation. The EPT for the first time integrates the hemodynamic and metabolic aspects of cell life at the organism scale. It is proved that the CVS activity is inversely associated with the activity mechanisms controlling the rates of both pulmonary ventilation and erythropoiesis. Under significant and chronic energy deficiency, the cells activate additional FSS mechanisms, materially supporting the biogenesis of mitochondria. The activity of FSS mechanisms forming the chemical composition of arterial and venous blood is in reciprocal relationships with the function of CVS. So, the EPT associates the function of CVS with energy and metabolic problems in cells. The EPT concerns both traditional and additional determinants of the MAP level. It is proved that stochastic combinations of these determinants force the MAP level to float. In particular, both the mitochondrial insufficiency and the chemical contamination of cytoplasm are capable of causing AH. The normal arterial pressure is always individual. Before correcting the altered arterial pressure, a complex medical examination for ascertaining the mitochondrial function, the status of the FSS mechanisms is recommended. The diagnosis of AH should be reoriented for detecting cellular abnormalities. The therapy of AH should be targeted at finding strategies for the optimizing the entire FSS function.

Cyclic AMP was a major molecule of interest, which played an important role as second messenger, contributing to signal transduction in the regulation of cellular function by peptide hormones. Afterwards, calmodulin and protein kinase C were discovered as modulator proteins of intracellular calcium signaling in hormonal action. After that, manifold proteins and their related molecules were demonstrated to participate in novel signaling pathways related to various cytokines in different types of cells. The author of this book discovered a novel protein known as regucalcin, which suppresses manifold signaling pathways related to transcription activity. After subsequent studies, regucalcin has been established to play a pivotal role in maintaining cell homeostasis and protecting it from disorders in various types of cells and tissues. This book will provide information regarding regucalcin that plays a pivotal role in cell homeostasis and disorder. This book is composed of eighteen chapters. These chapters include the following content: the discovery of regucalcin (Chapter One); chemical property and structure of regucalcin (Chapter Two); the regucalcin gene and its translational regulation (Chapter Three); the role of regucalcin in intracellular calcium homeostasis (Chapter Four); the role of regucalcin in cell nuclear function (Chapter Five); the role of regucalcin in protein synthesis and proteolysis (Chapter Six); the suppressive role of regucalcin in cell proliferation (Chapter Seven); how regucalcin protects apoptotic cell death (Chapter Eight); the protective role of regucalcin in oxidative stress (Chapter Nine); the involvement of regucalcin in liver metabolic disorder (Chapter Ten); the role of regucalcin in kidney cell homeostasis: involvement in renal failure (Chapter Eleven); the role of regucalcin in heart calcium signaling: insight into cardiac disorder (Chapter Twelve); the role of regucalcin in brain calcium homeostasis: disorder with aging (Chapter Thirteen); the role of regucalcin in bone homeostasis and osteoporosis (Chapter Fourteen); the role of regucalcin in lipid metabolism and diabetes (Chapter Fifteen); the role of regucalcin as a suppressor protein in carcinogenesis (Chapter Sixteen); the clinical aspects of regucalcin as a biomarker for disease (Chapter Seventeen); and conclusive remarks (Chapter Eighteen). This book will provide information regarding regucalcin and its pivotal role in cell homeostasis and disorder.

The subject matter of volume 1 of the 2-volumes-handbook focusses on leiomyosarcoma, low-grade and high-grade endometrial sarcoma and undifferentiated uterine sarcoma of the whole female genitalia. A separate extensive chapter is devoted to the variants of leiomyoma (angio-, lipo-, cotyledonoid, cellular, mitotically active, epithelioid and myxoid leiomyoma, leiomyoma with bizarre nuclei), atypical smooth muscle tumors (smooth muscle tumors with uncertain malignant potential), and disseminated peritoneal leiomyomatosis, benign metastasizing leiomyoma, and intravenous leiomyomatosis. Furthermore, endometrial stromal tumors - endometrial stromal nodules, endometrial stromal tumor with sex cord-like elements (ESTSCLE), uterine tumor resembling ovarian sex-cord tumor (UTROSCT) - and similar tumors are described in detail. The book provides a description at length of the epidemiology, etiology, pathological anatomy, prognosis, diagnosis, differential diagnosis, imaging and comprehensive therapy of each primary, relapsed, and metastasized tumor including surgery, chemo-, hormone- and radio- and targeted therapy. Another chapter is devoted to the prevention of subjecting sarcomas to inadequate surgical therapeutic measures under the assumed diagnosis of leiomyoma, and includes a diagnostic-therapeutic flowchart with a diagnostic score. The book aims to identify and provide diagnostic and therapeutic guidance. The listed tumor entities also constitute a particular diagnostic challenge for pathologists that contains numerous pitfalls and difficulties. This book, therefore, addresses gynecologists and pathologists in both clinical and private practice, but also surgeons and hemato-oncologists.

Accurate analysis of blood gases is vital to give information on a patient's respiratory and circulation state as well as the adequacy of resuscitation. This book guides the reader, with the help of clarifying cartoons, through the basic principles and a new and easy to grasp system of interpretation.

Sickle cell disease (SCD), an inherited hemolytic anemia, is associated with multiple acute and chronic complications such as painful vasoocclusive events, cerebral vasculopathy, priapism, and renal or lung disease. These complications are variable and unpredictable, and can be associated with significant morbidity and poor quality of life. This book covers several areas regarding pathology, diagnosis, complications, signs, symptoms and medical treatments. There are few studies in literature on the role of physiotherapy as a resource to prevent and treat locomotor system disorders, respiratory problems and painful crises in SCD individuals. This book highlights the role of physiotherapy in sickle cell anemia. A comprehensive and authoritative monograph, this book will be equally interesting to both established researchers and to graduate students interested in both genetics and the physical therapy field.

Acute myeloid leukemia (AML) is an aggressive bone marrow cancer associated with high morbidity and mortality and most commonly affects older patient populations. In this book, the clinical presentation of acute myeloid leukemia are presented. Other chapters present the differences in the outcomes of two subtypes of core binding factor (CBF) acute myeloid leukemia (AML); examine the occurrence of the Philadelphia chromosome in AML with core binding factor leukemia; and therapeutic options of older patients with AML.

Sickle cell hemoglobin (HbS) is the result of a single nucleotide change (GAG GTG) in the beta-globin gene, where valine replaces glutamic acid at the sixth amino acid position in the beta-globin chain. Sickle cell disease is a growing global health problem. The World Health Organization has estimated that 7% of the world population has the mutation and 300,000400,000 affected children are born every year. The disease progresses towards a severe chronic hemolytic anemia, and it shows a heterogeneous clinical course, related with different genetic factors. Despite the fact that all subjects with sickle cell disease (SCD) have the same single base pair mutation in the DNA, we further confirmed here that the severity of the clinical and hematological manifestations is extremely variable. Increasing evidence has indicated a role of oxidative stress in the vascular pathophysiology of SCD. The vascular endothelium is central to disease pathogenesis because it displays adhesion molecules for blood cells, balances procoagulant and anticoagulant properties of the vessel wall and regulates vascular homeostasis by synthesizing vasoconstricting and vasodilating substances.In addition, recent studies support the existence of a hyperoxidative status in SCD patients that may account, at least in part, for the clinical manifestations of these patients. Moreover, SCD patients with mild clinical outcomes were associated with low oxidative status, whereas high oxidative stress was related to severe phenotypes. Thus, the use of oxidative stress biomarkers may be important in the evaluation of the clinical condition of SCD patients, whereas the use of therapies to improve their redox status and increase NO bioavailability would be beneficial to reduce the severity of sickle disease. The global burden of SCD is now significantly increased and, thus, it is currently a public health problem around the world. This disease has passed from being a problem of the developing countries to affect many people in developed countries. This book summarizes the current epidemiology status and the latest discoveries in the pathophysiology of SCD, and the potential therapies that may improve the clinical course of this disease.

Transfusion Medicine is a key part of modern health care. It bridges the healthy community with the bedside in hospitals. It is the responsibility of the national blood program to provide an adequate supply of blood for all patients requiring transfusion, and to ensure the quality of blood and blood products for clinical use and the in-hospital transfusion chain. All products must be safe, clinically effective and of appropriate, and consistent quality. Every blood transfusion service, whether serving in a resource restricted environment or in an advanced ambience, should develop an effective quality (QS) and quality management system (QMS) to ensure the implementation of these strategies from vein to vein. The quality system and its management should cover all aspects of its activities and ensure full traceability (hemovigilance), from the motivation, mobilisation and selection of blood donors to the transfusion of blood and blood products to patients. It should also reflect the structure, needs and capabilities of the procurement establishments, as well as the needs of the hospitals and patients that it serves. Management commitment and support are essential for the development, implementation and monitoring of a national quality system and quality management system in order to ensure change management and continuous quality improvement. All staff should understand the importance of quality and the consequences of failure in the quality system (error management and cost effectiveness).

Neutrophil granulocytes are the primary defense cells of blood against bacteria, fungi, parasites, or thrombi. Their main weapons and signals are reactive oxygen species (ROS) that release photons. The activation of the assembly of their NADPH-oxidase, the few specific triggers and many specific or unspecific primers are of great physiological and pathophysiological importance in inflammation and in hemostasis. The neutrophils generate different types of photons and they can "see" them. The 300400 nm photons are the main signals and the photons of lowest wave length which seem to especially alert them in emergency. The present book presents research on the regulation of the neutrophil's ROS generation by different photons, by singlet oxygen (the excited "pro-drug" of photons), by important proteins, or by modulators of the eicosanoid metabolism that should not favor the generation of systemically circulating micro-thrombi.

Hemostasis (coagulation and fibrinolysis) is of importance in a broad range of medical disciplines. A high-quality hemostasis diagnosis enables a good therapy, which can be rather complicated without laboratory help. This yearbook gathers important contributions in this field and presents them in a coherent and logical format.

For many years the mammalian blood cell system has provided cell biologists and haematologists with one of the best experimental models in which to unravel how one stem cell -- the hematopoietic stem cell -- gives rise to many different types of progeny. Numerous models of lineage relationships have emerged, but the most influential of these, in which differentiating cells undergo a series of binary choices, has been increasingly challenged in recent years -- to the extent that the accumulation of new findings recently culminated in a Nature commentary suggesting that "the latest research will necessitate revision of textbook accounts". This book brings together contributions from many leading experts in the field of blood cell development who each discuss both the overall process of hematopoiesis and the origins and development of each of the cells of the blood and immune systems. It describes how new molecular, cellular and -- particularly -- transgenic tools are helping us understand the processes that control the lineage fates of hematopoietic stem and progenitor cells and how lineage-committed progeny develop along particular maturation pathways.

Granulocytes are a category of white blood cells characterised by the presence of granules in their cytoplasm. This book examines the characteristics of eosinophil granulocytes, its biological functions, its role in inflammation and its clinical significance in children. This book also reviews the role of granulocytes on the onset of tissue-destructive diseases when exposed to stress. In addition to the cases of disease, some physiological phenomena are also responsible for the stress-induced granulocytosis. Thus this book will also expands upon the role of granulocytes associated with various diseases and some physiological responses. Other topics discussed in this book include the role of basophil, the minute group of granulocyte, in tropical infections and in immune regulations; polymorphonuclear neutrophilic granulocytes (neutrophils), which are the most dangerous cells in the organism and their role in transient states of autoimmunity, and the effects of nucleoli change during differentiation and maturation of granulocytes.

Hematopoietic stem cell transplantation (HSCT) is the transplantation of blood stem cells derived from the bone marrow (that is, bone marrow transplantation) or blood. Stem cell transplantation is a medical procedure in the fields of haematology and oncology, most often performed for people with diseases of the blood, bone marrow, or certain types of cancer. Stem cell transplantation was pioneered using bone-marrow-derived stem cells by a team at the Fred Hutchinson Cancer Research Center from the 1950s through the 1970s led by E. Donnall Thomas, whose work was later recognised with a Nobel Prize in Physiology and Medicine. Thomas' work showed that bone marrow cells infused intravenously could repopulate the bone marrow and produce new blood cells. His work also reduced the likelihood of developing a life-threatening complication called Graft-versus-host disease. With the availability of the stem cell growth factors GM-CSF and G-CSF, most hematopoeitic stem cell transplantation procedures are now performed using stem cells collected from the peripheral blood, rather than from the bone marrow. Collecting stem cells provides a bigger graft, and does not require that the donor be subjected to general anaesthesia to collect the graft. Hematopoeitic stem cell transplantation remains a risky procedure with many possible complications; it has always been reserved for patients with life-threatening diseases. This book presents recent leading research in the field.

Warfarin (also known under the brand names of Coumadin, Jantoven, Marevan, and Waran) is an anticoagulant medication that is administered orally or, very rarely, by injection. It is used for the prophylaxis of thrombosis and embolism in many disorders. Its activity has to be monitored by frequent blood testing for the international normalised ratio (INR). It is named for the Wisconsin Alumni Research Foundation. Warfarin is a synthetic derivative of coumarin, a chemical found naturally in many plants, notably woodruff (Galium odoratum, Rubiaceae), and at lower levels in liquorice, lavender and various other species. Warfarin was originally developed as a rat poison; however, more modern poisons are much more potent and toxic (e.g., brodifacoum). Warfarin and contemporary rodenticides belong to the same class of drugs (coumarins) and both decrease blood coagulation by interfering with vitamin K metabolism. For this reason, drugs in this class are also referred to as vitamin K antagonists.

There are two dominant aspects which conclude the coagulation cascade: the importance of the tissue factor pathway in initiating clotting and the interaction between pathways. Two main pathways are recognised the extrinsic and the intrinsic. At the side of vascular injury endothelial cells are converted in a pro-thrombotic state or become detached to exposed circulating blood to thrombogenic constituents of the sub-endothelial matrix. Activation of platelets and formation of fibrin occur simultaneously and interdependently to effect haemostasis. The activated platelets express the receptor GPIb-IX-V complex that further strengthens the adhesion by linking to von Willebrand factor expressed on the sub-endothelial matrix. A platelet monolayer which covers the injured area recruits and aggregates activated platelets to form a platelet plug by linking to fibrinogen molecules. Activation of a series of inactive precursors leads to the formation of thrombin that cleaves fibrinogen to fibrin. The sequence of reactions interacting between factor X represents the common pathway of coagulation. Factor X can be activated in turn by either the tissue factor pathway or the contact activation pathway of coagulation, which is initiated by the complex of tissue factor and factor VIIa. The latter involves a series of zymogen protease reactions that are initiated by contact activation of factor XII to XIIa. As the haemostatic process starts, a series of inhibitory mechanisms is activated involving antithrombin III, protein C, protein S, the tissue factor pathway inhibitors 1 and 2 and platelet inhibitors (prostaglandin I2, nitric oxide). Fibrinolytic mechanisms assure the clot's remodelling and elimination in the prospect of restoring the vessels patency. During the fibrinolytic process plasmin cleaves polymerised fibrin to fibrin degradation products. The liver plays a predominant role in the regulation of haemostasis. By producing most clotting factors (except tissue factor TF) and inhibitors (antithrombin III, protein C, protein S, C1 inhibitor), as well as a number of the proteins involved in fibrinolysis (plasminogen, a2-antiplasmin), and by clearing from the bloodstream activated enzymes involved in clotting or fibrinolysis, the liver protects against both bleeding and overwhelming activation of coagulation. There is a common bleeding profile emerging in the overwhelming majority of liver diseases. The severity of documented coagulation disorders varies analogically to the degree of the hepatocellular injury. The importance of the coagulopathy is underlined by the incorporation of the coagulation parameters into prognostic scores assessing fulminant hepatic failure and cirrhosis. The purpose of this book is to review the coagulation profile in acute liver failure, liver cirrhosis, autoimmune cholestatic, viral and various hepatic diseases. Diagnostic and therapeutic modalities in coagulation defects in liver diseases are also reviewed.

The proposed book focuses on 'blood infections', a common group of haematology and infectious disorders in aspects relating to the tropical medicine. The book covers specifically the clinical aspects, scientific laboratory aspects, public health aspects, as well as the social sciences relating to these important diseases. The common blood infections, including other disorders, which relate to blood disorders are summarised, presented, and discussed. The book presents summative data from the molecular to the population scales, as well as additional metanalysis for important topics.