It has been generally accepted that angiogenesis is involved in the pathogenesis of hematological malignancies, like acute and chronic leukemia, lymphoma, myelodysplastic syndromes, myeloproliferative neoplasms and multiple myeloma. The extent of angiogenesis in the bone marrow has been correlated with disease burden, prognosis and treatment outcome. Reciprocal positive and negative interactions between tumor cells and bone marrow stromal cells, namely hematopoietic stem cells, fibroblasts, osteoblasts/osteoclasts, endothelial cells, endothelial progenitor cells, T cells, macrophages and mast cells, mediated by an array of cytokines, receptors and adhesion molecules, modulate the angiogenic response in hematological tumors. More recently, it has been emphasized the pro-angiogenic role of the so called “vascular niche”, indicating a site rich in blood vessels where endothelial cells and mural cells such as pericytes and smooth muscle cells create a microenvironment that affects the behavior of several stem and progenitor cells, in hematological malignancies.

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.

This book covers all aspects of chronic radiation syndrome (CRS) based on observations in a unique sample of residents of the Techa riverside villages in the southern Urals who were exposed to radioactive contamination in the 1950s owing to releases of liquid radioactive wastes. The opening chapters discuss the definition and classification of CRS, its epidemiology and pathogenesis and the pathoanatomy of CRS during the development and recovery stages. Clinical manifestations of CRS at the different stages are then described in detail and the dynamics of hematopoietic changes are thoroughly examined. In the following chapters, principles of diagnosis and differential diagnosis are discussed and current and potential treatment options, described. The medical and social rehabilitation of persons with CRS is also covered. This book, which casts new light on the condition, will be of value for all practitioners and researchers with an interest in CRS.

While advances in both the treatment of cancer and the management of its complications have led to significant improvement in patient survival, infections remain a significant cause of morbidity and mortality in patients with neo plastic disease. In this patient population, infection risk results from a complex interplay between the host’s underlying immunodeficiencies, local tumor effects and treatment-induced immunosuppression. New chemotherapeutic approaches and antimicrobial prophylaxis and treatment practices continue to shape the spectrum of infections in these patients. Clinicians who treat infections in cancer patients are continually challenged by the emergence of new pathogens and by the increasing antimicrobial resistance of established ones. The aim of this book is to emphasize unique aspects of management of infectious diseases in the cancer patient. With the increasing complexity of this patient population, optimal management requires a multidisciplinary approach and this fact is fully reflected in the contributions, all from recognized authorities in the field. Ultimately, it is hoped that this volume will assist specialists in infectious diseases and haematology/oncology in the diagnosis, management and prevention of infection and optimization of the overall care of patients with malignancies.

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 book, part of the series Rare Diseases of the Immune System, offers comprehensive, up-to-date coverage of the pathophysiology and management of the antiphospholipid syndrome (APS). Immunologic and genetic aspects are discussed and the pathogenic mechanisms responsible for such phenomena as APS-mediated thrombosis and pregnancy loss/complications are explained. The main clinical manifestations, classification criteria and diagnostic tools are identified, and close attention is paid to the nature of the involvement of various organs or organ systems in APS. Specific chapters describe the treatment of the different symptoms, therapies of value in avoiding recurrences, and innovative treatment approaches. The authors are senior experts in the field who are aided by younger fellows, ensuring that the book is also educationally oriented. This handy volume will be a valuable tool for postgraduates in training and professionals wishing to extend their knowledge of this specific syndrome.

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.

Blood science has become a cornerstone of multiple disciplines, including clinical chemistry, disease diagnosis, and therapeutic monitoring. Over the past decade, we have witnessed the advent of increasingly powerful proteomics technologies that allow greater fundamental insights into the blood proteome. These technological improvements have, in part, fuelled the quest for the discovery of novel blood-based biomarkers of disease. Serum/Plasma Proteomics: Methods and Protocols is a comprehensive resource of protocols for areas, pre-analytical through to analytical, of plasma and serum proteomics. Divided into five convenient sections, this detailed volume covers fractionation strategies for in-depth blood proteome analysis, defined procedures for blood collection, handling and storage, detailed protocols for performing both antibody-based and non-antibody based quantitative assays, proteome analysis of blood cell compartments, circulating nanomebraneous vesicles and blood-related fluids, and finally data management, statistical design, and bioinformatic challenges. This book, contributed to by leading experts in the field, provides a valuable foundation for the development and application of blood-based proteomics. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters contain introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, Serum/Plasma Proteomics: Methods and Protocols, with its well-honed methodologies, seeks to serve both professionals and investigators new to the field in an effort to further our knowledge of this fundamental science.

The haemostatic system is one the most important physiological systems for maintaining health and well being, and thus the investigation of the haemostatic system remains a research priority. Disturbances of the haemostatic system in the broader sense, such as heart disease and strokes, arguably constitute the single greatest contribution to non-infectious mortality in the world today. Therefore, understanding the laboratory methods to assess the haemostatic system is vital for the practice of complex clinical medicine. In Haemostasis: Methods and Protocols, experts in the field address the major components of the haemostatic system, general principles of haemostatic testing, and techniques used to assess various aspects of the haemostatic system, grouped according to their functional indications. Written in the successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, Haemostasis: Methods and Protocols provides an ideal guide to scientists of all backgrounds and serves an urgent need for further research to develop superior methods of assessing the haemostatic system in humans.

Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world. CLL has a highly varied clinical course. While advances in CLL therapy are noted, many patients still succumb to this illness. Like most progress in medicine, solid advances in the diagnosis, prognosis and treatment of CLL are rooted in an in-depth understanding of the basic and translational biology of CLL. In this book, CLL experts have contributed state-of-the-art summaries of various important aspects of CLL biology and have discussed the translational implication of such findings. This book, which is directed at physicians and researchers alike, aims to educate broadly and deeply. Intentionally, the many aspects and nuances of CLL clinical care that can only really be appreciated through direct patient care are not covered here, but instead, the book presents basic aspects of CLL that underlie many of the contemporary decisions that are made in CLL research and clinical settings. We hope that this book will critically inform the community and stimulate interest in CLL, which will ultimately translate into better CLL research, prognostication and therapy, with the end goal of providing a better outlook for patients afflicted with this common leukemia.

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.

Increased knowledge on the pathogenesis of hematologic diseases has been translated into diagnostic and prognostic applications. Hematopathology and laboratory hematology were among the first disciplines to embrace molecular diagnostics. Hematological Malignancies:Methods and Protocols, explores molecular-based assays frequently used in the routine diagnostic hematopathology and laboratory hematology. Many of these protocols were initially developed as research applications and were further refined as they transitioned to the diagnostic laboratory. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Hematological Malignancies: Methods and Protocols aids scientist in the continuing study of tests essential for contemporary laboratory diagnostics of hematological neoplasms.

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.

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 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.

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.

This book provides clinical practitioners and the research community with detailed information on the diagnosis, prognosis, and treatment of non-Hodgkin lymphoma, taking into account the significant growth in knowledge including multiple therapeutic advances that have been achieved over the past 5-10 years. The work is subdivided into epidemiology, pathogenesis, pathology, imaging, and therapy of the non-Hodgkin lymphomas. The full range of therapeutic options are examined according to the major subtypes of non-Hodgkin lymphoma and the most up-to-date information is provided on current standard treatment options, including stem cell transplantation as well as new cutting-edge therapeutics.