The blood system is multi-scale, from the organism to the organs to cells to intracellular signaling pathways to macromolecule interactions. Blood consists of circulating cells, cellular fragments (platelets and microparticles), and plasma macromolecules. Blood cells and their fragments result from a highly-ordered process, hematopoiesis. Definitive hematopoiesis occurs in the bone marrow, where pluripotential stem cells give rise to multiple lineages of highly specialized cells. Highly-productive and continuously regenerative, hematopoiesis requires a microenvironment of mesenchymal cells and blood vessels. A Systems Biology Approach to Blood is divided into three main sections: basic components, physiological processes, and clinical applications. Using blood as a window, one can study health and disease through this unique tool box with reactive biological fluids that mirrors the prevailing hemodynamics of the vessel walls and the various blood cell types. Many blood diseases, rare and common can and have been exploited using systems biology approaches with successful results and therefore ideal models for systems medicine. More importantly, hematopoiesis offers one of the best studied systems with insight into stem cell biology, cellular interaction, development; linage programing and reprograming that are every day influenced by the most mature and understood regulatory networks.

Circulation of blood is vital for the survival of vertebrates, including man. Mainly, it plays an important role in carrying food nutrients and oxygen to every tissue and organ and in removing all waste products and carbon dioxide. Any imbalance in the hemostatic and cardiovascular systems can lead to death and severe debility. A number of animals have developed mechanisms to target these systems and exploit the vulnerability. In some species (for example, snakes), such mechanisms are used to immobilize and kill the victim/prey, whereas in others (for example, insects, such as leaches, mosquitoes and ticks), they are used to provide a continuous supply of blood. These mechanisms include, but are not limited to, procoagulant and anticoagulant actions that affect the coagulation cascade and platelet aggregation, as well as altering vasodilatory responses. In all these various animals, these mechanisms have evolved to perfection over millions of years to support their survival. In last 3-4 decades, due to the efforts of scientists from various backgrounds including biology, protein chemistry, molecular biology, pharmacology, hematology, and structural biology, significant progress in understanding the structure-function relationships, as well as the mechanism of action have been made in a number of exogenous factors that affect blood coagulation, platelet aggregation and vasodilation from various animals. These exogenous factors have contributed significantly to the development of research tools as well as providing new therapeutic agents. With the increase average age of the population coupled with changes in life style in recent years, there has been a significant increase in cardiovascular and hematological disorders. Thus scientists in both academic institutions as well as the pharmaceutical industry are developing better therapeutic agents to improve the quality of life. This impetus has lead to the search for novel agents from various sources that interfere with cardiovascular and hematalogical processes. Although at first glance exogenous factors appear to function as 'villains', several life-saving drugs have been developed based upon these factors. Such drugs or drug leads include those that inhibit the angiotensin converting enzymes (Captopril and Enalapril), that block platelet receptors (Eptifibatide and Tirofiban), or that digest thrombotic plugs (Alfimeprase and bat plasminogen activator) to name a few. Several new and exciting success stories are currently unfolding. In this book, recent studies on some of the exogenous factors that play crucial roles in cardiovascular and hematological disorders are reviewed in order to consolidate the efforts in this area of research and to recruit new, talented researchers. The 25-30 review chapters, each written by experts in their field, compiled herein are devoted to exogenous factors affecting platelet aggregation, anticoagulant and procoagulant proteins, fibrinolytic proteins and hypotensive agents (For details see, Contents of the Book). This book is intended to help to create elevated awareness and enthusiasm in the field of exogenous factors. I believe that this book will provide greater impetus to the search for novel proteins based on naturally occurring exogenous factors. This will be the first book dealing extensively with exogenous factors in the last 25 years. The book will provide a ready reference to the different approaches used to solve complex problems in protein chemistry and pharmacology of exogenous factors. The book will update our understanding of the structure-function relationships and mechanisms of action of exogenous factors and provide great insights into future directions for solving the remaining challenges.

First published in 1925, this two-volume work deals with the blood's role in respiration. This first volume analyses the effect of high altitudes on the blood's ability to retain and diffuse oxygen. The text is illustrated with diagrams, maps and photographs relating to the changes human physiology undergoes at altitude, including changes in circulation rate, pulse and the nature of red corpuscles. This book will be of value to anyone with an interest in the history of medicine or in haematology.

First published in 1925, this two-volume work deals with the blood's role in respiration. This second volume deals with haemoglobin as a chemical substance. The text is illustrated with diagrams and drawings relating to, among other things, haemoglobin's specificity, its manufacture in the body and how it is affected by temperature changes. This book will be of value to anyone with an interest in the history of medicine or in haematology.

This is the third edition of a well-received compendium of information and guidance on the diagnosis and management of the various oncological diseases that are encountered in children and adolescents. In the new edition a chapter on Rare Tumors was added. For each disease entity, fundamental facts are provided that will be relevant for a range of professionals - hospital physicians, specialist nurses, psycho-oncologists, physiotherapists, family doctors and pediatricians. Compared with the first edition all chapters have been updated. Throughout, rapid orientation is ensured by the clear, consistent layout and the concise, lucid style. Pediatric Oncology: A Comprehensive Guide is an excellent, easy-to-use reference that belongs on the shelf of every practitioner who encounters or treats malignancies in the pediatric age group. Pediatric Oncology is teamwork! Fundamental facts for all those involved in diagnosis and management - even social worker, pedagogic teachers, religious care persons.

There have been many changes in the field of coagulation during the past decade. New concepts of epidemiology of risk factors for thrombosis now help clinicians predict who is more likely to form clots after surgery, or after being placed on oral contraceptives. New anticoagulants have the potential to redefine how patients with atrial fibrillation and venous thrombosis are managed. There are new forms of recombinant clotting factors which have changed our approach to hypofibrinogenemia and von Willebrand's disease. Newer antiplatelet agents are available and their use in patients receiving cardiac stents has mushroomed. The management of thrombosis in the setting of pregnancy has changed over the past decade, as well as the way clinicians approach women with multiple miscarriages. An entire new class of compounds, the thrombopoietins, are available to treat individuals with immune thrombocytopenic purpura (ITP). The Coagulation Consult covers major topics of interest to hematologists who are asked to consult on individuals with coagulation related diseases, and encompasses the field's most recent developments. This "case-directed" book describes state-of-the-art approaches to patients with bleeding and clotting disorders, as well as laboratory tests for coagulation. Chapters include different vignettes, focus on typical clinical consult questions, and lay out specific types of treatment. Practicing clinicians being confronted with coagulation consult students, residents, fellows and attending physicians will find this unique text an invaluable resource for some of the newer areas of coagulation science, therapy and pharmacology.

Typically, manuals of pediatric hematology-oncology are written by specialists from high-income countries, and usually target an audience with a sub-specialist level of training, often assisted by cutting-edge diagnostic and treatment facilities. However, approximately 80% of new cases of cancer in children appear in mid- and low-income countries. Almost invariably, general practitioners or general pediatricians without special training in oncology will look after children with malignancies who enter the health care system in these countries. The diagnostic facilities are usually limited, as are the treatment options. The survival figures in these conditions are somewhere below 20%, while in high-income countries they are in the range of 80% for many childhood cancers. Pediatric Hematology-Oncology in Countries with Limited Resources is the only book of its kind to provide specific guidance applicable to limited resource settings and builds up from the foundation of general practitioner or general pediatrician competence. Written and edited by leaders in the field, this manual educates physicians on the essential components of the discipline, filtered through the experience of specialists from developing countries, with immediate applicability in the specific healthcare environment in these countries.

MRI provides the best means of imaging the bone marrow directly and of non-invasively assessing its composition. Normal age-related bone marrow changes, alterations related to red marrow reconversion, and pathological bone marrow processes generally conform to certain patterns that reflect the underlying marrow changes and can be clearly recognized on MR images. In addition to conventional pulse sequences, advanced MRI techniques such as Dynamic Contrast-Enhanced MRI and Diffusion-Weighted Imaging depict marrow changes at the microvascular and cellular level respectively. This book provides radiologists with in-depth information on the MRI appearances of normal, abnormal and treated marrow following a structured, pattern-based approach. MRI findings for various diseases that affect the bone marrow, particularly those of a malignant nature, are presented in detail. MRI pattern recognition not only offers a systematic approach to image interpretation and diagnosis but also has prognostic implications with regard to some disease entities. Each chapter includes a wealth of high-quality images, together with Key Points summarizing the most important information. In addition to radiologists, practitioners with an interest in hematology and oncology will find this textbook-atlas to be a valuable resource for the latest, clinically relevant advances in bone marrow imaging.

This book provides clear instruction on the surgical treatment of joint problems in adult hemophilia patients. The procedures applicable to specific joints, including the shoulder, elbow, hip, knee and ankle, are carefully reviewed with the aid of high-quality illustrations. The surgical treatment of articular hemophilic pseudotumors and bone cysts is also considered. In addition, clinically relevant information is provided on a range of topics, such as the treatment of hemophilic hemarthrosis, the imaging of hemophilic joints, hematological perioperative management, anesthesia, rehabilitation and pharmacoeconomics. Finally, the controversial issues of postoperative thromboembolic prophylaxis and the role of COX-2 inhibitors in hemophiliacs are reviewed. The guidance provided draws on both the authors' extensive personal experience and an in-depth review of the pertinent literature. The book offers an excellent, up-to-date account of knowledge on musculoskeletal problems and approaches to joint surgery in adults with hemophilia. It will be of value to orthopedic surgeons, rehabilitation physicians, hematologists, radiologists and pharmacy researchers.

This Brief provides a comprehensive introduction to the control of blood flow in the brain. Beginning with the basic physiology of autoregulation, the author goes on to discuss measurement techniques, mathematical models, methods of analysis, and relevant clinical conditions, all within this single volume. The author draws together this disparate field, and lays the groundwork for future research directions. The text gives an up-to-date review of the state of the art in cerebral autoregulation, which is particularly relevant as cerebral autoregulation moves from the laboratory to the bedside. Cerebral Autoregulation will be useful to researchers in the physical sciences such as mathematical biology, medical physics, and biomedical engineering whose work is concerned with the brain. Researchers in the medical sciences and clinicians dealing with the brain and blood flow, as well as industry professionals developing techniques such as ultrasound, MRI, and CT will also find this Brief of interest.

This book comprehensively describes the physiological changes and consequences that occur in humans during spaceflight. It specifically presents the adaptations of the cardiovascular and the respiratory system. Specific changes occurring after 10, 20 or more days in space are depicted. Furthermore, the book explains various effective countermeasures that are required upon return of the astronauts to Earth. The book is a must-have for all biomedical and clinical researchers in the field of cardiovascular biology and respiration, and a fascinating reading for all interested laymen, who wish to understand a bit more about spaceflight research and technology.

There have been many changes in the field of coagulation during the past decade. New concepts of epidemiology of risk factors for thrombosis now help clinicians predict who is more likely to form clots after surgery, or after being placed on oral contraceptives. New anticoagulants have the potential to redefine how patients with atrial fibrillation and venous thrombosis are managed. There are new forms of recombinant clotting factors which have changed our approach to hypofibrinogenemia and von Willebrand s disease. Newer antiplatelet agents are available and their use in patients receiving cardiac stents has mushroomed. The management of thrombosis in the setting of pregnancy has changed over the past decade, as well as the way clinicians approach women with multiple miscarriages. An entire new class of compounds, the thrombopoietins, are available to treat individuals with immune thrombocytopenic purpura (ITP).

"The Coagulation Consult"covers major topics of interest to hematologists who are asked to consult on individuals with coagulation related diseases, and encompasses the field s most recent developments. This case-directed book describes state-of-the-art approaches to patients with bleeding and clotting disorders, as well as laboratory tests for coagulation. Chapters include different vignettes, focus on typical clinical consult questions, and lay out specific types of treatment. Practicing clinicians being confronted withcoagulation consult students, residents, fellows and attending physicians will find this unique text an invaluable resource for some of the newer areas of coagulation science, therapy and pharmacology."

This third edition expands upon the role of anticoagulants in clinical practice. In addition, it summarizes new developments in the field and provides evidence-based guidelines for the use of anticoagulants in routine day-to-day practice. The Handbook of Thromboprophylaxis Third Edition is a key resource for all physicians with an interest in thromboprophylaxis.

In this newly updated second edition, Reinhold Munker and his distinguished colleagues offer a concise up-to-date summary of the fundamentals of clinical hematology, including all the most recent developments. Their comprehensive survey presents the essential clinical facts concerning malignant and nonmalignant blood diseases, detailing diagnostic methods, angiostatic drugs, the very latest therapies, classifications, scientific controversies, and clear treatment recommendations. They also illuminate the scientific basis needed to understand the new diagnostic and treatment methodologies, infections relevant for hematology, the molecular pathogenesis of many hematologic disorders, storage disorders, and the new cellular therapies for these malignant disorders.

Reproductive hemostasis: A global approach to a global challenge

A hemostatic change in women through their reproductive lifetime is emerging as an issue of global importance. No wonder, as obstetric hemorrhage remains a major cause of maternal mortality in both developed and developing countries. Thrombophilias and pulmonary embolisms are a threat to maternal and fetal well-being.

"Hemostasis and Thrombosis in Obstetrics & Gynecology" provides a framework for assessing and managing hemostatic disorders in women. Written by an international team, it provides globally applicable guidelines for obstetric hematology. The practical approach to clinical management includes: Hematologic changes in pregnancyRed cell disordersPlatelet disordersInherited and acquired thrombophiliaInherited bleeding disordersPostpartum hemorrhage

Blood and bleeding disorders in women can be managed by obstetrician-gynecologists or hematologists, separately or together. "Hemostasis and Thrombosis in Obstetrics & Gynecology" provides specialists from both disciplines with the information necessary to manage their patients effectively.

This book provides a state-of-the-art approach to the molecular basis of hematologic diseases and its translation into improved diagnostics and novel therapeutic strategies. Several representative hemato-oncologic malignancies are analyzed in detail: acute lymphoblastic leukemia, acute myeloid leukemia, B-cell Non-Hodgkin lymphomas, multiple myeloma, chronic lymphocytic leukemia, chronic myeloid leukemia, myelodysplastic syndromes, and myeloproliferative neoplasms. Experts in the field describe the molecular methods applied for modern diagnostics and therapies, such as hematopoietic stem cell transplantation, donor recipient matching, banking of biological material, analyses of post-transplant chimerism, and minimal residual disease monitoring. The volume concludes with an extensive section comprising thorough step-by-step protocols of molecular techniques in hematology, all of them validated in the authors' own laboratories.

Multiple myeloma is a plasma cell malignancy characterized by complex heterogenous cytogenetic abnormalities that accounts for 1.4% of all cancers, and approximately 10% of hematologic malignancies. The clinical manifestations of multiple myeloma include lytic bone lesions, cytopenia, hypercalcemia, renal dysfunction, hyperviscosity of the blood, immunodeficiency, and peripheral neuropathy. Based on the clinical and genetic data, probably all cases of multiple myeloma arise from an asymptomatic monoclonal gammopathy of unknown significance. The exact mechanism of the transition from MGUS to overt multiple myeloma is still not well understood. Recent oncogenomic studies have further advanced our understanding of the molecular pathogenesis of multiple myeloma. This book will give a comprehensive overview of the genetic and molecular epidemiology of multiple myeloma in order to get a more refined and conclusive understanding of this disease.

New techniques to study cell signaling and function can develop at a staggering pace; however, many approaches are as valid today as on the day they were established. Thus, the main aim of Platelets and Megakaryocytes: Volume 3, Additional Protocols and Perspectives is to complement the first two volumes published in 2004 by adding recently developed state of the art techniques. Conveniently divided into three sections, this detailed volume covers techniques to study platelet function, approaches to investigate megakaryocyte function, and perspectives on important overall concepts in the field of megakaryocyte and platelet biology. Written in the highly successful Methods in Molecular Biology (TM) series format, methods chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and vital tips on troubleshooting and avoiding known pitfalls. Authoritative and up-to-date, Platelets and Megakaryocytes: Volume 3, Additional Protocols and Perspectives adds a wealth of new expertise for the labs of scientists working in this key biological area of study.

In this thoroughly revised and expanded third edition of the highly praised classic, The Principles of Clinical Cytogenetics, a panel of hands-on experts update their descriptions of the basic concepts and interpretations involved in chromosome analysis to include the many advances that have occurred in the field. Among the highlights are a full chapter devoted to advances in chromosome microarray, soon to become a standard of care in this field, as well as an update on chromosome nomenclature as reflected in ISCN 2009. Other features include an update on automation to reflect the current state of the art, an update on hematopoietic neoplasms to reflect the new WHO guidelines, and updates on all regulatory changes that have been implemented. Cutting edge and readily accessible, The Principles of Clinical Cytogenetics, Third Edition offers physicians who depend on the cytogenetics laboratory for the diagnosis of their patients, students in cytogenetics programs, graduate and medical students studying for board examinations, cytogenetics technologists, and cytogeneticists a clear understanding of what happens in the cytogenetics laboratory to facilitate accurate and timely diagnoses.

In the last decade, there has been a remarkable explosion of knowledge in hematologic cancer from basic molecular biology and pathology to clinical therapy. This has led to many new advance and insights in the understanding of pathobiology of malignant hematology. New knowledge of disease molecular pathology, cytogenetic, epigenetic and genomic alterations have provided new strategies to attack and eradicate tumor cells at molecular level and significantly impacted our current therapeutics for hematological malignancies. The recent and ongoing rapid expansion of knowledge in this area has become extensive, dynamic and diffuse over the literature and research publications. This has led to the need to capture and compile the new and current information about hematologic cancer with special emphasis on translation from molecular pathobiology to targeted therapeutics. In this book experts from around the world share their thoughts and knowledge about the pathobiology of hematologic cancer, as well as their view on current treatment approaches and future development in these malignant hematologic diseases. This book is well suited for hematology residents, fellows and hematology-oncology physicians, hematopathologist as well as basic research scientist in the area of hematologic malignancies.

Myelodysplastic syndromes (MDS) are the most common hematological malignancies involving mostly the elderly population. The major morbidity relates to patients' symptomatic cytopenias.MDS was previously named as "preleukemia " or " smoldering leukemia" as the lack of terminal cells in MDS and because about 25% of all cases progresses into acute myeloid leukemia. According to various reports the annual incidence of MDS ranges widely from 2-12 per 100.000, increasing to 30-50 cases per 100.000 among persons aged 70 or older. It is believed that the true incidence of MDS have been underestimated however it seems to be comparable to that for multiple myeloma and chronic lymphocytic leukemia. In the past decade much progress had been made; we know more on the disease pathology, there is more emphasis on the care and more targeted therapy had been invested. Athors provide updated knowledge in this book on all clinically important aspects of the disease. Hot topics of our days are discussed in chapters by outstanding and well known scientists from all over the world. We would offer this product both for medical students and postgraduates as well as for all who are interested in this very exciting and fast progressing field of hematology. With this work authors should call attention on the disease for decision makers in healt care systems as well.

This concise, clinically focused pocket handbook assembles and synthesizes the latest developments and trends in the diagnosis and treatment of CML and provides an authoritative and convenient summary of the latest progress in TKI trials, the molecular monitoring of CML responses, and the development of new therapies to overcome resistance and improve patient care. Chronic myeloid leukemia (CML) is a rare type of leukemia (1-2 per 100,000 people) but is the most common chronic myeloproliferative neoplasm. CML remains a key model for the improved understanding of the pathophysiology of a malignancy at a molecular level; CML was the first cancer to be associated with a recurring chromosome abnormality, which generates the Philadelphia (Ph) chromosome and its associated fusion gene BCR-ABL1. The clinical outcome for patients with CML has changed dramatically in the past 15 years and this has been due to the development of tyrosine kinase inhibitors (TKIs), compounds that inhibit the activity of the oncogenic BCR-ABL1 protein. A number of first-, second- and third-generation TKIs are now available for the treatment of CML, although a number of treatment challenges remain, not least the development of treatment-resistant CML. Parallel to the development of specific drugs for treating CML, major advances have been made in the field of disease monitoring and standardization of response criteria.

The extravasation of cytotoxic agents can result in severe local tissue damage and medical emergencies during tumour therapy. This revised compendium is intended to help clinicians assess any situation speedily and with certainty. The general section of the book includes topics such as predisposition, prevention, type of harm, general measures in handling extravasated drugs, specific antidotes, and documentation. In the 2nd edition, the scientific information contained in the general section and relating to the actual substances has been updated. The substance specific part of the book includes detailed instructions on handling more than 50 cytotoxic drugs, to initiate targeted measures. Templates for an extravasation set, overview tables, documentation sheets, and patient information, as we as a CD-ROM are included to support clinical practice. The book is the outcome of a consensus of an interdisciplinary working group that has collected and systematically reviewed all published literature on the topic.

In the last decade, technical improvements have changed the inventory of many research laboratories. New techniques and discoveries continuously give rise to observations that result in the de?nition of new research objectives. In the past, - search departments were clearly demarcated. Nowadays, technology that is shared by all lines of research stimulates convergence of research interests. This also - plies to cardiovascular research. Vascular occlusive disease is now core business for researchers employed by cardiology, vascular surgery, vascular medicine, - diology, cell biology, chemistry, physiology, and many other areas. Knowledge on actual research development is shared by researchers with different skills. It is sometimes dif?cult to acquire expertise when a researcher feels his experimental work could be improved by introducing a new research technique. In this book, the investigator will ?nd an overview of recent developments that are relevant for research in general but cardiovascular research in particular. Genomics, p- teomics, microarray, RNAi, stem cells, and progenitor cells are just some phrases that have become increasingly prevalent in literature in the last few years and that are recognized by many, but are fully understood by few. In this book, experts share the most appreciated new developments and techniques in cardiovascular research. We hope that this book will help the reader who is working in the ?eld of cardiovascular research to understand and critically appreciate current research, and that it will help improve the quality of experimental work. Dr G.

This handbook offers timely investigation of current pharmaceutical trends, clinical guidelines, novel treatments, and ongoing pipeline developments, including ground-breaking advances in the use of novel oral anticoagulants. Atrial fibrillation (AF) affects an estimated 1-2% of the population and is the most common cause of sustained cardiac arrhythmia. Critically, the number of patients developing AF is expected to double in the next five decades, leading to increased incidence of stroke, heart failure and other serious thromboembolic events.