This chapter covers non-hereditary causes of bleeding and thrombosis, which are referred to as acquired disorders that arise as a consequence of another primary disorder that may be hereditary or acquired. It names a number of acquired haemostatic disorders and describes their causes. It also discusses how acquired disorders of haemostasis can affect routine coagulation screening tests and how routine and specialist haemostasis assays can be employed to diagnose acquired disorders of haemostasis. The chapter explains that acquired bleeding disorders occur more frequently than inherited forms and are more common in hospitalized patients. It mentions disseminated intravascular coagulation (DIC), which results from excessive activation of coagulation exacerbated by loss of regulatory and localization mechanisms.
Acquired disorders of haemostasis
Anaemia 1: The bone marrow, micronutrients, and disease in other organs
Andrew Blann and Sukhjinder Marwah
This chapter describes anaemia as the major and clinically significant disease of red cells, causing a great deal of morbidity and mortality. It examines how problems with the bone marrow, micronutrients such as iron and vitamins, and disease in other organs can lead to anaemia. It also describes the pathological consequences of low and high levels of iron. The chapter talks about the effects of the poor supply of vitamins B12 and B6 and folate to the bone marrow. It outlines how diseases in different body organs can lead to anaemia and suggests how the laboratory can diagnose these conditions.
Anaemia 2: Haemolysis
Andrew Blann and Sukhjinder Marwah
This chapter focuses on the destruction of red blood cells, called haemolysis. It explains that haemolysis can be classified as an external factor acting on essentially healthy red cells, or as the destruction of red cells with defects of haemoglobin, the cell membrane, or in metabolic enzymes. It lists the different causes of the inappropriate destruction of red blood cells and clarifies the relationship between gene mutation and anaemia. The chapter describes the major features of the haemoglobinopathies and outlines how mutations in genes for membrane components and enzymes can lead to anaemia. It also highlights haemolytic anaemias, which are generally caused by a shortening of the lifespan of the red cell and failure of the bone marrow to be able to compensate for this reduced lifespan.
Bleeding disorders and their laboratory investigation
Gary Moore and David Gurney
This chapter covers bleeding disorders that arise from hereditary or acquired abnormalities of coagulation factors, von Willebrand factor (VWF), platelets, and blood vessels. It reviews the main laboratory tests available to biomedical scientists in order to identify and characterize bleeding disorders. It also describes the principles and interpretation of coagulation screening tests, platelet function analysis, factor assays and raw data assessment, and inhibitor screening and measurement. The chapter explains that bleeding disorders occur when components of haemostasis are deficient to an extent that confers a tendency to bleed excessively. It emphasizes how the type, site, and severity of haemorrhage can give important clues to whether a haemostatic disorder is present and the areas of haemostasis that are affected.
This chapter introduces the major blood-borne parasites that cause disease in humans and looks at their parasitic life cycles. It talks about how morphological characteristics are important for accurate diagnosis, and it covers laboratory tests that are available to biomedical scientists for the detection of blood parasites. It also describes the appearances of parasites in Romanowsky-stained blood films. The chapter elaborates that blood-borne parasites target specific organs and species for different stages of their life cycles, noting that the nature of each life cycle and the target organs involved dictate the clinical symptoms of each infection. It mentions eosinophilia, which is a likely haematological effect of arthropods such as head lice and scabies mites.
Case studies in haematology
Andrew Blann, Gavin Knight, and Gary Moore
This chapter reviews case studies that imply that haematology and its diseases encompass many different themes, not only red cells, white cells, or haemostasis alone. It presents three cases that bring together many of the diverse characteristics of haematology and demonstrates how its different aspects interact in defining a diagnosis and supporting clinical management. The first case study focuses on a morbidly obese 62-year-old woman that has an artificial hip joint on the left and an artificial knee joint on the right, which caused her to be 90% bed-bound with a persistent fever. The second case study is about a 43-year-old male employed as a steel worker, who complains about sore throat, fever, muscular aches, pains, and a general feeling of being tired all the time. The last case study includes a 49-year-old man who works as a warehouse supervisor that complains about a sharp, low back pain that has been present since he had an accident, a series of headaches, and a feeling of being more tired than usual.
Clinical Use of Blood Components
This chapter explores the function of blood in vivo and the body's response to anaemia and bleeding. It begins with an understanding of the basic circulatory physiology and the structure and function of the components of blood. The chapter then offers an overview of the coagulation cascade, plasma fractionation, and recombinant technology. It describes the different blood components available and their appropriate and inappropriate use based on best practice national guidelines. Next, the chapter looks at the benefits of transfusion therapy and the alternatives available to using allogeneic blood. It then analyses how good communication, standards, audit, and review of product use will aid appropriate use of blood components. The chapter also presents national initiatives designed to facilitate the appropriate use of blood.
Compatibility Testing and Adverse Effects
This chapter assesses the process of compatibility testing and how it applies to each type of blood component. It describes the various crossmatch methods used in laboratories to determine compatibility, and explains when and why each crossmatch method either may or may not be used. The chapter also outlines the various national guidelines regarding pre-transfusion compatibility testing, then details the role the laboratory has in the investigation of an adverse reaction. Next, the chapter distinguishes between the UK Serious Hazards of Transfusion (SHOT) reporting scheme and the incident reporting requirements of the Medicines and Healthcare products Regulatory Agency (MHRA). It cites a number of UK regulations, guidelines, and recommendations.
Dr Gary W. Moore, Gavin Knight, and Dr Andrew D. Blann
Haematology is composed of five parts. The first part acts as an introduction to the topic and looks at major haematology parameters and techniques as well as haemopoiesis and bone marrow. The second part looks at red blood cells, white blood cells, and anaemia. The third part covers haematological malignancies and introduces classification systems. The fourth part considers normal haemostasis and examines bleeding disorders, thrombophilia, acquired disorders of haemostasis, and anticoagulation. Finally, the text ends with different case studies in haematology.
Haematopoietic Stem Cell Transplantation and Stem Cell Plasticity
Ruth Morse and Saeed Kabrah
This chapter focuses on the biology of haematopoietic stem cells (HSC) transplants. It first defines the term “stem cells” (SC), and notes that the initial all-encompassing SC is represented by the “totipotent” SC which has the capacity to produce all the tissues of an embryo. The chapter also argues that the most well-known and utilized SCs are those of the bone marrow (BM), which early in the twentieth century were shown to develop into a range of different blood cell types including those of the myeloid lineage and lymphoid lineages. The chapter then moves to explain the various sources and methods of stem cell collection. It explores the clinical and laboratory requirement involved in stem cell transplantation. The chapter concludes by discussing the plasticity of haematopoietic stem cells and how this may be exploited for personalized medicine.
Haemolytic Disease of the Fetus and Newborn
This chapter examines the pathophysiology of haemolytic diseases of the fetus and newborn (HDFN). Here it considers fetal and neonatal anaemia and alloimmunization events. It seeks to understand blood-group incompatibilities that cause HDFN, including partial D antigens. It discusses the current clinical management of HDFN. The chapter also details the immunology of maternal alloimmunization to paternally inherited fetal antigens, feto-maternal IgG trafficking, the biochemistry of bilirubin detoxification, and clinical interventions and assessment by ultrasound. Near the end, the chapter shows the proposed mechanisms of action of prophylactic anti-D, and cellular assays to predict the severity of the disease. It then demonstrates the implementation of fetal blood-group genotyping in the management of HDFN.
Haemopoiesis and the bone marrow
This chapter outlines the origin and development of blood cells, which is the process of haemopoiesis. It explains that haemopoiesis is the regulated development of blood cells as they progress from being precursor stem cells in the bone marrow to fully functioning mature cells found in the blood. It also stresses the importance of learning about haemopoiesis as it is the key to understanding several pathological processes, including anaemia, autoimmunity, and leukaemia. The chapter lists the major components of bone marrow and describes the mechanisms of haemopoiesis, including the significance of growth factors. It explores the complex nature of the molecular genetics of blood cell development and the value of the analysis of bone marrow.
Haemostasis and anticoagulation
Gary Moore and Jane Needham
This chapter outlines the reasons for anticoagulant therapy, mode of action and use of therapeutic agents, laboratory assays for monitoring treatment, and associated clinical services for patient care. It highlights the importance of anticoagulant management and associated clinical risks, and it demonstrates how to monitor anticoagulant therapy in the laboratory. It also promotes awareness for hereditary or acquired conditions that can influence treatment outcomes, including interacting drugs and models of clinical services. The chapter outlines the risks associated with having an inherited or acquired thrombophilia defect, medical conditions that can lead to thrombosis, and events or environment that lead to blood stasis. It highlights important differences between causes and treatment for arterial and venous thrombosis.
Human Blood Group Antigens
This chapter focuses on how blood groups represent some of the best examples of the clinical implications of human polymorphism. It traces the existence of blood-group antigens and antisera. During the second half of the twentieth century, serology revealed all clinically significant blood groups. The chapter then explains the new molecular techniques that permitted the identification of protein species involved in blood-group antigen expression by the small-scale purification (immunoprecipitation) of those involved. It also looks at the completion of the first membrane protein to be sequenced, glycophorin A (GPA), which happened in 1975. Towards the end, the chapter explores the significant blood-group active genes, then considers what constitutes a polymorphic trait.
Human Leucocyte Antigens (HLA) and Their Clinical Significance
This chapter reviews the human leucocyte antigens, the genes of which are found within the major histocompatibility complex (MHC), and how the detection and matching of the genes and gene products has contributed to the success of transplantation and the study of human disease. It begins by defining the Human Leucocyte Antigens (HLA) system. The chapter explores the role of the HLA system in transplantation and transfusion, then shows the principles of matching for haemopoietic stem cell transplantation, solid organ transplantation, and platelet transfusion. The chapter also studies the methods and technology for HLA typing and antibody testing used in the HLA laboratory. Finally, the chapter investigates the key immunological pathways targeted by immunosuppression, then looks at the hurdles to overcome in xenotransplantation.
Human Platelet Antigens (HPA) and Human Neutrophil Antigens (HNA) and Their Clinical Significance
This chapter describes the nomenclature of human platelet antigens (HPA) and human neutrophil antigens (HNA). It presents the common principles involved in the immunohaematology of red cells and the immunohaematology of platelets and granulocytes. The chapter then outlines the most important HPA and HNA. It explores the principles, techniques, and problems in detecting HPA and HNA and associated antibodies. The chapter also investigates the clinical management and problems associated with the management of neonatal alloimmune thrombocytopenia (NAIT) cases. It discusses the role of platelet transfusion in other platelet immune disorders, and the processes of immune destruction affecting platelets. Finally, the chapter reports the other types of clinical interventions that are used to manage the range of clinical conditions associated with HPA and HNA antibodies.
Immune-Mediated Red Cell Destruction
This chapter shows how and why red blood cells (RBCs) are destroyed in the body, in vivo, by antibodies. It first describes the difference between intravascular and extravascular haemolysis. The chapter then defines the role of antibodies and complement in red cell destruction. It outlines the clinical significance of red cell antibodies and the use of the direct antiglobulin test (DAT). The chapter then shifts to detail the causes of haemolytic transfusion reactions, and the types of autoimmune haemolytic anaemias and the problems associated with finding compatible blood. Finally, the chapter examines how red antibodies can cause hyperacute rejection in solid organ transplant. It also considers the phenomenon of passenger lymphocyte syndrome.
Introduction to Basic Immunology and Techniques
This chapter describes the laboratory and scientific aspects of the transfusion of human blood and products or components made from blood, and the transplantation of tissues and stem cells. It examines the historical background to the science of transfusion and transplantation. The chapter also outlines the various components of the immune system and the functioning of the humoral immune system. The chapter then switches topics to describe the agglutination of human red cells by serum of other humans, which is a difference within a species, rather than between species. It then presents two other major developments that enabled advances to be made in transfusion practice. The first is the use of plastic bags for the collection of blood, instead of glass bottles. The second major advance was the introduction of monoclonal antibody technology.
An introduction to classification systems: lymphoid neoplasms
This chapter provides the pathobiological background or a brief description of the most common and interesting cases of lymphoid neoplasms. It outlines the main differences between precursor and mature cell neoplasms, and it considers key recurrent cytogenetic abnormalities associated with precursor lymphoid neoplasms. It also identifies key genetic mutations associated with selected lymphoid disease states and indicates how these mutations contribute to leukaemo- and lymphomagenesis. The chapter differentiates between the main plasma cell neoplasms and explains the key clinical and laboratory findings in each. It describes the common T-lineage malignancies and provides an outline of the role of anaplastic lymphoma kinase (ALK) dysregulation.
An introduction to classification systems: myeloid neoplasms
This chapter examines a range of haematological neoplasms, such as leukaemias, which are recognized by the World Health Organization (WHO). It explains how haematological neoplasms can be subdivided into myeloid or lymphoid lineages and then subdivided further according to various cellular, molecular, genetic, and clinical features. It also describes the common translocations identified in haematological neoplasms and their role in classification. The chapter explores the molecular mechanisms underpinning the development and behaviour of selected haematological neoplasms. It compares and contrasts the disease entities classified as myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN), recognizing the importance of MDS/MPN overlap conditions.