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Dr Gary W. Moore BSc DBMS CSci FIBMS CBiol MRSB CertMHS Consultant Biomedical Scientist Department of Haemostasis and Thrombosis Viapath at Guy’s and St. Thomas’ Hospitals, London Gavin Knight BSc (Hons) MSc SFHEA FIBMS CSci Principal Lecturer, School of Pharmacy and Biomedical Science University of Portsmouth Dr Andrew D. Blann PhD FRCPath FRCPE FIBMS CSci Consultant Clinical Scientist, Blood Science Solutions, Birmingham Hon. Senior Lecturer, University of Birmingham Medical School Hon. Senior Lecturer in Biomedical Science, Wolverhampton University Haematology Second edition 1 Fundamentals of Biomedical Science Preview - Copyrighted Material

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Page 1: Material Copyrighted...Dr Gary W. Moore BSc DBMS CSci FIBMS CBiol MRSB CertMHS Consultant Biomedical Scientist Department of Haemostasis and Thrombosis Viapath at Guy’s and St. Thomas’

Dr Gary W. MooreBSc DBMS CSci FIBMS CBiol MRSB CertMHS

Consultant Biomedical ScientistDepartment of Haemostasis and Thrombosis

Viapath at Guy’s and St. Thomas’ Hospitals, London

Gavin KnightBSc (Hons) MSc SFHEA FIBMS CSci

Principal Lecturer, School of Pharmacy and Biomedical Science University of Portsmouth

Dr Andrew D. BlannPhD FRCPath FRCPE FIBMS CSci

Consultant Clinical Scientist, Blood Science Solutions, Birmingham Hon. Senior Lecturer, University of Birmingham Medical School

Hon. Senior Lecturer in Biomedical Science, Wolverhampton University

HaematologySecond edition

1

Fundamentals of Biomedical Science

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1Great Clarendon Street, Oxford, OX2 6DP,

United Kingdom

Oxford University Press is a department of the University of Oxford. It furthers the University’s objective of excellence in research, scholarship,

and education by publishing worldwide. Oxford is a registered trade mark of Oxford University Press in the UK and in certain other countries

© Gary Moore, Gavin Knight, and Andrew Blann 2016

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First edition 2010Impression: 1

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Introduction to haematology

Alexis Henley, Gary W. Moore, Gavin Knight, and Andrew D. Blann

This chapter introduces haematology, not only as the science of the study of blood itself but also about how the subject relates to other disciplines in pathology. You will also get a feel for haema-tology in the wider aspects of healthcare, and how as haematologists you will need to relate to your colleagues working in other disciplines within pathology, in hospitals, and with the profes-sional bodies.

Learning objectives

After studying this chapter, you should confidently be able to:

■ Explain key aspects of the science of haematology.

■ Appreciate the role of the biomedical scientist in the haematology laboratory.

■ Describe the role of haematology in the provision of healthcare.

■ Outline the overlap of haematology and other pathology disciplines.

■ Comment on the role of professional and regulatory bodies.

1.1 What is haematology?Put simply, haematology is the study of blood. The haematology laboratory in a healthcare setting is concerned with the diagnosis and monitoring of diseases of the blood and blood-forming organs. Blood cells are manufactured in bone marrow and released into the peripheral blood once they are mature. Blood is a dynamic and crucial fluid providing molecular and cellular transport and many regulatory functions. Blood interfaces with all organs and tissues in the body, carrying essen-tial substances such as oxygen and nutrients to the cells, and waste products away from cells to the excretory organs. As such it has a very important role in ensuring adequate whole-body physiology and homeostasis. It follows that adverse changes to the blood will have numerous consequences, many of which can be serious and life-threatening.

1

bone marrowSoft tissue located inside hollow bones responsible for the production and maturation of blood cells.

peripheral bloodThe blood that is contained within the circulatory system.

homeostasisThe maintenance of stable physiological systems.

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1 HAEMATOLOGY AND HAEMOPOIESIS4

Conversely, adverse changes to organs and tissues may translate into changes in the make up of the blood that are secondary to the primary disease. It is in this latter capacity that blood can be used in the clinical laboratory for the detection and monitoring of various diseases and their treatments.

Blood is composed of approximately 45% blood cells, which are classified into three main types:

• Red blood cells (RBC) that carry oxygen to the tissues.

• White blood cells (WBC) that function primarily as defence against infection.

• Platelets that prevent blood loss at sites of injury by combining with specialized proteins to form a clot.

The remaining 55% is plasma, which is an aqueous solution that acts as the transport me-dium for blood cells, dissolved nutrients, and plasma proteins, including those involved in blood coagulation.

Biomedical scientists working in the haematology laboratory perform an array of diverse blood tests that are concerned with the investigation of the number, structure, and function of the cellular elements of blood and the investigation and control of bleeding and clotting disorders.

Blood tests are performed either on whole blood, plasma or serum depending on the investi-gation required. Blood is collected by venepuncture into specially designed bottles. Blood tests that require whole blood or plasma are collected into blood tubes containing anticoagulants to prevent the blood clotting before it is analysed; blood for tests on serum is collected into plain tubes. Anticoagulants are also used in the clinic as therapeutics to reduce the risk of a clot forming within the body: full details are in Chapter 17.

SELF-CHECK 1.1

Name the three different types of blood cell.

1.1.1 A classification of haematologyHaematology tends to be considered under the three main areas of red blood cells, white blood cells and haemostasis, which are then further subclassified.

Red blood cells

Haematologists are interested in the number and function of red blood cells, their size, and the amount and quality of the haemoglobin that they carry. By far the most common condition concerning red blood cells is anaemia, which is a reduction in the oxygen-carrying capacity of the blood arising from reduced or abnormal haemoglobin inside the red blood cells, and/or reduced numbers of red blood cells. At the polar extreme are the diseases erythrocytosis and polycythaemia, where there are too many red blood cells, leading to a high haemoglobin level. Anaemia leads to clinical symptoms of leth-argy, weakness, dizziness, and feeling faint. If the anaemia worsens, patients can experience shortness of breath, palpitations, headaches, and sore mouth and gums. The different types of anaemia result from a variety of underlying medical disorders.

Common causes of anaemia are:

• Iron deficiency, which results in a defect in production of the haem (iron-containing) component of haemoglobin due to the lack of ferrous iron.

• Vitamin B12 and/or folate deficiency, which affect the production of DNA.

• Other diseases and conditions such as malignancy, renal disease, liver disease, lead poisoning, and infection.

• Hereditary conditions, such as sickle cell disease and thalassaemia where there is a defect in the haemoglobin molecule.

• Acute and chronic blood loss.

Cross referencesRed blood cells and their associated disease states are described in

further detail in Chapters 4–6.

White blood cells and associated disease states are described in

further detail in Chapters 8–12.

Platelets and their associated disease states are described in further detail in Chapters 11, 13, 14, 16 and 17.

blood coagulationThe process where specialized proteins interact to form a clot (in conjunction with platelets).

serumThe fluid that remains after the blood has been allowed to clot.

venepunctureThe process of obtaining intravenous access to obtain a sample of blood via a needle.

anticoagulantA physiological or pharmacological mechanism that retards clotting processes.

haemostasisThe interplay of cellular and molecular processes that maintain blood fluidity and also generate blood clots at sites of injury, regulate clot formation, and degrade clots.

haemoglobinMetalloprotein inside red blood cells that is responsible for oxygen transport.

erythrocytosisA condition characterized by a high red blood cell count, generally a response to a factor such as hypoxia or increased levels of erythropoietin. The haematocrit and haemoglobin are also increased. It is described in more detail in Chapter 3.

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1 INTRODUCTION TO HAEMATOLOGY 5

White blood cells

Leucocytes (white blood cells), of which there are five recognizable types found within the periph-eral blood, are part of the immune system. They help protect the body against infections caused by microbes such as viruses and bacteria. The most common serious disease of white blood cells is leukaemia, a type of neoplasia.

The haematology laboratory investigates the number of each type of white blood cell in the periph-eral blood and whether they are mature or immature cells.

• Raised numbers of normally functioning white cells can be seen in bacterial, viral, and fungal infections where extra cells become available to deal with the microorganisms.

• Raised numbers of immature white cells are commonly found in many leukaemias. These cells represent the uncontrolled proliferation of malignant clones in the bone marrow or lymphoid tissue entering the peripheral blood.

• Low numbers of white blood cells can be caused by some medications and cytotoxic chemotherapy. Reduced numbers of white cells can be seen in diseases such as aplastic anaemia. The consequence of depleted numbers of white blood cells is the body’s inability to fight infection effectively.

Haemostasis

Haemostasis comprises an integrated group of balanced cellular and molecular processes designed to minimize the loss of blood upon damage to blood vessels, i.e. haemorrhage, a condition which can be life-threatening. However, excessive and/or inappropriate activity of the coagulation system, generally resulting in thrombosis, can also be dangerous. Unimpaired platelet function and certain coagulation proteins are crucial to effective haemostasis.

Haematologists are also involved in the diagnosis and management of patients whose blood has a predisposition to clot and of those people who have an underlying bleeding disorder, e.g. haemophilia.

The haemostasis laboratory plays a key role in monitoring patients who are receiving medication for thrombosis. Anticoagulant medication inhibits the ability of the blood to clot, but too much can cause the patient to haemorrhage, therefore regular monitoring is required.

In addition to the categories of diseases discussed above haematologists are also involved in the diagnosis of some parasitic blood infections, such as malaria. (See also Box 1.1.)

SELF-CHECK 1.2

What are the three main areas of haematology?

Cross referencesAnaemia—this major spectrum of diseases of red blood cells is

described in Chapters 5 and 6.

Leukaemia and related disorders are described in further detail in Chapters 9–12.

infectionThe presence of sufficiently high numbers of a microorganism that invoke clinical symptoms and provoke a defensive response.

leukaemiaA haemoproliferative disorder characterized by increased numbers of blood cells in the bone marrow and peripheral blood.

neoplasiaAn abnormal proliferation of cells that can be benign or progress to malignancy. (The word comes from the Greek neo = new, plasia = formation.)

cloneA cell, group of cells, or organism descended from and genetically identical to a single common ancestor.

All the diseases you have just been introduced to, and their detection in the laboratory by biomedical scientists, are discussed in more detail in the chapters that follow:

■ Chapter 2 introduces basic blood tests

■ Chapter 3 describes how the blood cells develop

■ Chapters 4–6 consider the red blood cell in health and disease

■ Chapter 7 introduces you to blood-borne parasites

■ Chapter 8 discusses white blood cells in health and disease

■ Chapters 9–12 introduce biological mechanisms leading to cancer of the blood, and the classification of these cancers.

■ Chapters 13–17 focus on haemostasis and the consequences of its failure

■ Chapter 18 consolidates some key issues in haematology in three complex case studies

BOX 1.1 What will this book achieve?

polycythaemiaA malignancy of red blood cells that causes too many to be produced. This leads to a high red cell count, haematocrit and haemoglobin. It is described in more detail in Chapter 11.

sickle cell diseaseAn inherited disorder of haemoglobin of varying severity. The name arises from the deformed shape the red blood cells take when the abnormal haemoglobin inside them polymerizes.

thalassaemiaA spectrum of inherited disorders of haemoglobin where there is an imbalance in globin chain production.

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1 HAEMATOLOGY AND HAEMOPOIESIS6

1.2 The role of the biomedical scientist in the haematology laboratoryBiomedical scientists carry out a wide range of laboratory tests to produce and interpret results that assist in the diagnosis and treatment of disease. The biomedical scientist specializing in haematology plays an essential role in supporting many hospital departments, such as accident and emergency, intensive care, operating theatres, special care baby units, and oncology. Without the contribution of the biomedical scientist these departments could not function as effectively.

The biomedical scientist working in the haematology laboratory is particularly important in sup-porting medical colleagues in the specialist areas of haemato-oncology, haemostasis, and hae-moglobinopathies. Indeed as your career progresses you may decide to specialize in one of these subdisciplines.

Many of the analytical techniques employed in haematology are also common to other pathology disciplines, e.g. immunoassay, genetic techniques (such as polymerase chain reaction), and micros-copy, which will equip you with transferable scientific skills, whilst other scientific methods are specific to haematology.

1.2.1 Common haematology techniquesWhilst haematology laboratories employ a wide range of analyses and analytical techniques there are some that are performed in large numbers on a daily basis throughout the UK. Many are basic screen-ing tests that form a diagnostic springboard for the initiation of follow-up investigations to identify and characterize specific disease states. (See also Box 1.2.)

Full blood count

The full blood count (FBC) is the single most commonly performed routine haematological blood test. It provides information on the number and size of red blood cells, white blood cells and platelets. It also measures the concentration of haemoglobin in the blood. The FBC is performed on highly spe-cialized automated analysers. This is a first-line test that is important in providing information on the type of follow-up investigation that may be required.

Blood films

Microscopy has an important role in the haematology laboratory as it enables the size, maturity, shape, content and other aspects of the physiology and pathology of blood cells to be assessed. A drop of blood is smeared onto a glass slide, dried, fixed and stained. Different components within par-ticular cells take up different stains so that they can be identified under a microscope. Blood films are used to investigate the various causes of red cell, white cell, and platelet disorders, and parasitic infec-tions of the blood. Haematological disease, and many disorders generating secondary haematological

aplastic anaemiaA serious disease where the bone marrow does not produce enough blood cells.

haemorrhageExcessive bleeding caused by a breakdown in haemostasis.

thrombosisThe process of the (generally inappropriate) formation of blood clots.

haemophiliaHereditary bleeding disorder caused by a deficiency in clotting factors.

malariaAn infectious disease found in tropical and subtropical regions. It is caused by protozoan parasites of Plasmodium species that are carried by mosquitoes.

oncologyThe area of medicine that deals with the development, diagnosis, treatment, and prevention of tumours.

haemato-oncologyCancers of the blood.

haemoglobinopathyDisease (such as thalassaemia and sickle cell disease) resulting from mutations in the globin genes and so abnormal haemoglobin synthesis.

Cross referenceHaemorrhage, thrombosis, and haemostasis are fully explained in Chapters 13–16.

One fascinating aspect of practice as a biomedical scientist in haematology is that the nature of many haematological diseases is evident when marrying FBC data with blood film appear-ances and other results. You literally see the disease for yourself when examining a blood film. Indeed, it is not unknown for biomedical scientists to discover serious disorders such as leukaemia and malaria before they are clinically evident to medical staff and that can be immensely rewarding.

BOX 1.2 A rewarding career

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1 INTRODUCTION TO HAEMATOLOGY 7

changes, give rise to a vast array of abnormal morphological findings that can be apparent on a stained blood film. Building up the knowledge and skills to be able to identify the myriad morphologi-cal changes that can be encountered in haematological practice will be one of the biggest and most fascinating challenges of your career. Bone marrow is also examined in a similar way to whole blood.

Erythrocyte sedimentation rate

An erythrocyte sedimentation rate (ESR) is performed to empirically assess the inflammatory re-sponse to tissue injury and response to treatment, and so has clinical value in monitoring diseases like rheumatoid arthritis. However, an abnormal ESR may also be present in non-inflammatory disease such as cancer and anaemia, and many pregnant women have an abnormal ESR that may be entirely due their pregnancy and not ill health. The ESR is a physical property not of blood cells, nor of the plasma proteins, but of whole blood, and measures the rheological properties of the blood. The ESR is a test that can be performed either manually or on a specific autoanalyser. A test allied to the ESR is plasma viscosity, which is determined by water content and macromolecular components. Pathological alterations in levels of certain plasma constituents will alter plasma viscosity and inform diagnostic decisions.

Coagulation screen

This group of tests measures the time it takes for blood plasma to clot in response to specific stimuli, and identifies which particular areas of the biochemistry of blood coagulation may be abnormal. These are front-line tests routinely employed in hospitals to monitor patients who are bleeding or undergoing an operation. A test called the International Normalized Ratio (INR) is used to monitor patients who are on the therapeutic anticoagulant drug warfarin. Coagulation screens can be per-formed manually, but are more commonly performed on automated coagulation analysers.

Haematinic assays

This type of assay directly measures the concentration of factors such as iron, ferritin, vitamin B12, or folate to indicate nutritional and other causes of anaemia. Due to the type of random access analyser that performs the analyses haematinic assays may be performed in the biochemistry laboratory. The results of haematinic assays often dictate the type of therapy patients receive when they are anaemic.

Immunophenotyping

Flow cytometry is a highly specialized technique that allows the measurement of multiple physical characteristics of a single cell, such as its size and its granularity. The technique can be extended by pretreating cells with fluorochrome-conjugated monoclonal antibodies, which are then analysed in an instrument called a fluorescence flow cytometer. This technique, immunophenotyping, can determine the presence of certain molecules on the surface of the cell, and is essential for the accurate identification of a number of types of haematological malignancy.

Haemoglobin-variant detection

Separation methods such as electrophoresis and high-pressure liquid chromatography (HPLC) are used to identify variants of haemoglobin. These techniques are important in the diagnosis of hae-moglobinopathies such as sickle cell anaemia and thalassaemia.

Genetic techniques

Analysis of DNA is an important tool for the investigation of many inherited haematological disorders such as haemophilia and haemoglobinopathies. Genetic analysis is also important in the management of leukaemia because specific gene defects can indicate the severity of disease and the intensity of the treatment required.

Cross referenceDetails of the full blood count are provided in Chapter 2, and the importance of the bone marrow, is outlined in Chapter 3, but these are also a theme throughout the book.

morphologicalThe external appearance (of cells).

rheumatoid arthritisAn inflammatory disease that mainly affects the joints.

rheology/rheologicalThe study of the physical nature of blood or plasma. The principal measurements are the ESR and viscosity.

International Normalized RatioA system established by the WHO to standardize prothrombin time (PT) reporting system for patients receiving vitamin K antagonist oral anticoagulants.

warfarinA common vitamin K antagonist oral anticoagulant drug used to prevent the recurrence of thrombosis.

ferritinThe main storage protein for iron.

fluoresence flow cytometryCells treated with fluorescent dyes move in a liquid stream past a laser beam. Analysis is based on the size, granularity, and fluorescence of the individual cell.

electrophoresisMigration of dispersed particles (perhaps molecules) relative to a fluid under the influence of an electric field.

high-pressure [/performance] liquid chromatographyColumn chromatography technique used to separate, identify, and quantify compounds.

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1 HAEMATOLOGY AND HAEMOPOIESIS8

All these techniques, plus many others, are described in detail in later chapters within this book.

Point-of-care testing

Traditionally, blood tests are performed in a centralized laboratory by specifically educated, trained, and registered practitioners, who are usually biomedical scientists. Technological advances have led to the development of portable analytical devices with limited or single test repertoires that allow basic pathology tests to be performed away from the centralized laboratory, either at the bedside, in the outpatient clinic, or in the General Practice. This has had two major effects on professional practice:

1. Biomedical scientists can, on occasions, practise away from the central laboratory and enjoy a degree of patient contact.

2. Other healthcare staff, and even patients, can access and operate the devices.

Point-of-care testing is more commonly available for analytes associated with the biochemistry laboratory (such as blood glucose), one major exception being the INR for warfarin monitoring.

1.2.2 Additional roles of biomedical scientistsAs well as analytical investigations, biomedical scientists have responsibility for a number of other important areas that maintain effective laboratory practice.

Quality management

A key role of all biomedical scientists is to ensure that the quality of the results produced by each technique and operator is maintained, which is achieved in a variety of ways. The laboratory will par-ticipate in external quality assessment (EQA) programmes for all the tests they perform. Examples of such a scheme are those run by the National External Quality Assessment Scheme (NEQAS) in the UK. Additionally internal quality controls (IQC) are performed to monitor the performance of an assay in real time.

Quality is also maintained by assessing the competency of laboratory staff, at initial training and at regular intervals, and by the laboratory operating a quality management system which encompasses document control and a rolling audit programme. Much of the document control centres around standard operating procedures (SOP), which as the name suggests, are documents that explicitly state how every aspect of a given procedure must be performed. This is a way of ensuring, as far as is possible, that every test is performed the same way—irrespective of the operator—in order to achieve consistent high-quality results. The SOPs are regularly reviewed and updated where necessary.

Pathology laboratories have their own quality assessment body, Clinical Pathology Accreditation (UK) Ltd (CPA UK). Each medical laboratory is expected to meet a number of defined standards and is assessed at least every four years against these standards. It is a requirement of CPA UK that all laboratories have a quality manager who ensures compliance to International Organization for Standardization (ISO) 15189 accreditation standards. (See also Boxes 1.3 and 1.4.)

Health and safety

The clinical laboratory can be a dangerous place. The nature of the work means that potentially bio-hazardous blood specimens are handled and that the analytical work involves the use of chemicals many of which may be harmful if not controlled. Although their use has declined substantially over the last decade, some laboratories still use radioactive isotopes in investigations.

As with all workplace environments, laboratories are subject to legislative health and safety re-quirements, e.g. Control of Substances Hazardous to Health (COSHH). Risk assessments must be performed for each procedure in the laboratory’s repertoire. Laboratory personnel must be exposed to minimal risk, which is achieved in a variety of ways, including the use of personal protective equip-ment such as laboratory coats, gloves, and safety goggles. Automated procedures have reduced the necessity of the individual coming into direct contact with blood and reagents. In hospital laboratories a senior biomedical scientist is often designated as the health and safety officer.

Cross referenceThere is a chapter in the Biomedical Science Practice volume in this series that covers quality assurance in more detail.

risk assessmentThe determination and documentation of the quantitative or qualitative value of risk related to a specific situation/procedure and a recognized hazard.

Cross referenceHealth and safety is covered in more detail within the Biomedical Science Practice volume in this series.

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1 INTRODUCTION TO HAEMATOLOGY 9

Training and education

Many hospital laboratories have approved training status from the Institute of Biomedical Science (IBMS, the UK’s principal professional body in biomedical science). Training is overseen by a biomedi-cal scientist who is designated as the training officer and is often the link between the laboratory and the university. Laboratories may have BSc students on work placement or have staff attending univer-sity to obtain higher degrees. Biomedical scientists must prove that they are competent to perform each individual procedure/assay, and competency assessment records are kept for each employee.

In order to be maintained on the government’s register of approved health care practitioners (the Health and Care Professions Council, explained in more detail in Section 1.4.3), ongoing continu-ing professional development (CPD) must be undertaken. Each laboratory needs to demonstrate how it assists personnel to develop, and this includes ensuring each member of staff has successfully completed their annual CPD return. This may be achieved by organizing journal clubs or ongoing lecture/tutorial programmes.

As additional educational resources, many departments arrange in-house lectures/courses deliv-ered by internal and external speakers. Early in your career you will likely be a delegate, but later you could be asked to contribute presentations of your own. Further into your career, when you have amassed sufficient knowledge and experience, you may be invited to be a visiting lecturer at a univer-sity to educate the next generation of biomedical scientists.

SELF-CHECK 1.3

What are the major roles of the biomedical scientist in the haematology laboratory?

It is important to recognize the difference between EQA and IQC because they assess the quality of results in different contexts.

External Quality Assessment (EQA)A central agency supplies all registered laboratories with blood samples for analysis by locally employed techniques for each test performed. Local results are compared to those from laboratories throughout the UK to identify consensus or performance anomalies. It must be noted that EQA is only a retrospective evaluation of performance.

Internal Quality Control (IQC)Samples of known values that are analysed simultaneously with patient samples to monitor the performance of an assay.

BOX 1.3 Quality definitions

Health and Care Professions CouncilThe government body that regulates professionals in a variety of healthcare disciplines to ensure they are fit to practice.

Continuing professional developmentThe process of maintaining currency in one’s field via practical and educational activities that maintain up to date and informed professional practice.

CPA UK is under the umbrella of the United Kingdom Accreditation Service (UKAS). All pathology laboratories must be registered with CPA UK. The standards cover quality, health and safety, personnel, and analytical processes.

BOX 1.4 Clinical Pathology Accreditation (UK) Ltd

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1 HAEMATOLOGY AND HAEMOPOIESIS10

1.3 The role of haematology in the provision of healthcareThe UK spends 4% of its annual healthcare budget on pathology. Haematology laboratories are performing an increasing number and broader range of tests than ever before for the healthcare community.

As healthcare professionals we aim to provide a framework for the identification (diagnosis) and treatment of human disease. Broadly speaking, this can be envisaged as comprising two stages: initially when the individual self-refers to their general practitioner (GP), which is termed the primary care setting; then, however, any particular case may require additional investigations or treatments not generally available to the GP, so that the patient is referred to and then cared for by a hospital, which is secondary care. Some haematology tests have a role in primary care, where the GP may call on the pathology laboratories for help in diagnosis and (if needed) to monitor the effects of treatment. However, the haematology laboratory is important in virtually all aspects of secondary care.

Exceptionally difficult or complex cases may demand additional tests that could be beyond the scope of a routine laboratory. If so, then referral to a specialist centre at a different hospital may be required—this is described as tertiary care. Such specialist centres are often linked to a university, i.e. will be part of a university teaching hospital.

There are many ways to classify human disease. As an example to give you a flavour of the contribu-tion of haematology diagnostics to overall healthcare, one model is to consider three broad areas of pathology—cancer, connective tissue disease (such as rheumatoid arthritis, osteoarthritis, and their allied conditions), and cardiovascular disease (to include its risk factors such as diabetes and dys-lipidaemia). Together, these constitute 70–80% of the healthcare burden of the developed world. The remaining conditions include, for example, infectious diseases and psychiatric illness.

For many patients, one of the first presentations to their GP will be for a group of symptoms that could indicate anaemia. As you will see in Chapters 4–6, this may be due to problems with the red blood cells but may also be due to disease of the blood vessels, heart disease, and/or lung disease. This group of symptoms may be caused by cardiovascular disease, by a connective tissue disease, or by cancer—the symptoms of anaemia (whether actual anaemia or not) are common in all three condi-tions. However, patients with cancer or connective tissue disease will have a separate group of signs and symptoms, as well as abnormal blood results.

The winter months bring their excess burden of colds and influenza, especially to the elderly, and so with it sequelae such as bacterial throat infections and chest infections. A common prescription to deal with these infections is broad-spectrum antibiotics. These infections can have several effects on the blood—notably an increase in the white blood cell count and changes to the ESR. However, the necessity for a prolonged prescription of antibiotics over several months may suggest something more serious, especially if accompanied by symptoms of anaemia, such as leukaemia where the ma-lignant cells are made at the expense of normal cells. The late stages of this serious disease include an increased risk of bruising and bleeding, signs that can be investigated by the haematologist.

Cardiovascular disease can lead to heart failure, irregular heartbeat or cardiac arrest. The most common reason for cardiac arrest is the presence of clots within the coronary arteries that prevent blood flow to the myocardium. Once deprived of this blood, with its life-giving oxygen, the mus-cle cells of the heart will fail and die, leading to an often terminal heart attack. It follows that the causative process is the development of a clot (thrombus), which may erupt from areas of damage (lesions) within the coronary artery itself, or by thrombus formation elsewhere in the body which travels to the heart and there becomes lodged. Thus, one role of the haematology laboratory in the care of the patient with cardiovascular disease is to provide knowledge of the coagulation system. However, patients with cancer are also at risk of thrombosis, and, conversely, a small proportion of people who find themselves with an unexplained clot in the legs or the lungs have an undiagnosed cancer.

SELF-CHECK 1.4

What percentage of the annual healthcare budget is spent on pathology?

myocardiumHeart muscle.

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1 INTRODUCTION TO HAEMATOLOGY 11

Thus the haematology laboratory can help with the diagnosis and management of all three of the major human disease groups.

1.3.1 The overlap with other pathology disciplinesAlthough most biomedical scientists will specialize within a particular pathology discipline, it is im-portant to remember that each area contributes information towards a complete understanding of disease.

Blood transfusion

The position of the blood transfusion laboratory is clear, as in the vast majority of pathology de-partments the haematology and blood transfusion laboratory are scientifically and organizationally linked. Most biomedical scientists specializing in haematology will also have trained in blood transfu-sion. However, the many differences between these two arms of biomedical science are emphasized by the requirement to deal with each part in a separate textbook of this series.

The blood transfusion laboratory is concerned with the preparation of blood and blood products for transfusion, which includes compatibility testing between donor and recipient blood. The findings of anaemia, thrombocytopenia, or abnormal blood coagulation in the haematology laboratory can lead to requests for the blood transfusion laboratory to prepare red cells, platelets, or plasma for infu-sion into the patient.

Immunology

Immunology involves the study of the immune system and its disorders. Deficiencies of the immune system are investigated together with their association to infection, tumour growth, autoimmunity (e.g. rheumatoid arthritis), and allergies. The immunology laboratory is also involved in tissue-matching for organ transplants, and plays an important role in monitoring and treating patients with acquired immune deficiency syndrome (AIDS).

There is a clear link between the immunology and haematology disciplines. Immunology is concerned with white cell function and antibody production and haematology looks at white cell numbers, morphology, and some aspects of function. There is an inevitable crossover; for instance, leukaemias are recognized initially from the FBC, blood film, and bone marrow results and then char-acterized using immunophenotyping, all of which are performed by biomedical scientists in the hae-matology laboratory.

Biochemistry

The biochemistry laboratory is concerned with the study of changes in the chemical composition of blood and other body fluids to assist in the diagnosis and monitoring of disease, e.g. blood sugar in diabetes and liver function tests in liver disease. The laboratory is also involved in other analyses, such as toxicology investigation, prenatal screening for Down syndrome, and for neural tube defects.

There is overlap with haematology as conditions such as liver disease may also exhibit abnormal blood cells and deranged blood clotting. Renal function is investigated in the biochemistry laboratory, but if disease in this organ is present the resultant anaemia is diagnosed and monitored in a haematol-ogy laboratory. In this instance, the anaemia occurs due to reduction in levels of a hormone (erythro-poietin) produced in the kidneys that stimulates red cell production.

Bacteriology

Bacteriology, which is a branch of the microbiology laboratories, is involved in the identification of microorganisms that cause infections such as food poisoning, bacterial meningitis, and septicae-mia. Microorganisms are cultured and subjected to tests to establish their identity. Subsequent tests identify which antibiotics will be effective in treating the specific organisms that have been isolated. Infection is also of interest to the haematologist as it can result in a high white blood cell count; in

blood transfusionThe science of ensuring the safe transfer of blood and other substances from one person to another.

Cross referenceBlood transfusion is the subject of a separate textbook in this series, namely Transfusion and Transplantation Science.

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1 HAEMATOLOGY AND HAEMOPOIESIS12

cases of severe septicaemia very abnormal clotting is seen accompanied by depleted platelet num-bers, which have severe consequences for the patient. White cells can adopt atypical morphology in response to infection.

The bacteriology laboratory is increasingly involved in the monitoring of hospital acquired infec-tions and also investigates for gut parasites. Malaria is a parasitic infection with a life-cycle phase that occurs partly in the bloodstream and thus it is detected in the haematology laboratory, as are other blood-borne parasites.

Virology

The virology laboratory diagnoses infectious diseases such as hepatitis, rubella, chlamydia, human immunodeficiency virus (HIV), and influenza. Various types of hepatitis virus cause liver disease which will lead to both abnormal biochemistry and haematology results. The treatment for conditions such as infection with HIV can lead to a low white blood cell count, therefore the haematology laboratory will be co-involved in the monitoring of the patient’s treatment. Some viral infections, such as infec-tious mononucleosis (glandular fever), present with characteristic morphological changes in white cells that are detected both microscopically and serologically in the haematology laboratory.

Histopathology

The histopathology laboratory processes biopsy, surgical resections, and post-mortem tissue samples. The most closely related area to haematology is examining trephines from bone marrow and biopsies from lymphoma patients. A co-morbidity to many types of cancer is an anaemia, and cancer may also cause a deep vein thrombosis. Consequently, an abnormal haematology profile may be the first indi-cation of a malignancy that may be ultimately be diagnosed by histopathologists.

Cytology

In cytology, cell samples are examined for the presence of cancerous and precancerous cells, including cervical screening. As outlined above, cancer may cause both an anaemia and a deep vein thrombosis.

Cytogenetics

Cytogeneticists study chromosomes, which is key to understanding genetic disease. Cytogenetic anal-ysis plays an important role in the diagnosis and management of diseases such as haemoglobinopathy, leukaemia and lymphomas, and clinicians need to marry the results from both laboratories when diagnosing subtypes of haematological malignancies and making treatment decisions.

Stem cell laboratory

Stem cell laboratories prepare harvested stem cells for transfusion into patients. Stem cells are impor-tant for the treatment of some patients with haematological malignancies. Cytogenetics and stem cell laboratories are only found in teaching hospitals.

SELF-CHECK 1.5

Which discipline is most closely related to haematology?

1.4 The role of the professional bodyA professional body is a learned organization that represents a particular profession by maintaining control or oversight of the legitimate practice of that profession. It seeks to further the profession, the interests of individuals engaged in that profession, and to safeguard the public interest.

Cross referenceYou will meet blood-borne parasites and their laboratory detection in Chapter 7.

Cross referenceInfectious mononucleosis and its investigation are discussed in detail in Chapter 8.

Cross referenceCytogenetic analysis will be discussed in much greater detail in Chapters 9–12.

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1 INTRODUCTION TO HAEMATOLOGY 13

The major professional body for biomedical scientists employed in UK pathology laboratories is the Institute of Biomedical Science. However, the diversity in the biomedical sciences and the requirement to specialize often demands additional professional bodies. As far as haematology is concerned, this is the British Society for Haematology, which predominantly represents medical practitioners but also other healthcare staff whose practice involves/encompasses haematology.

1.4.1 The Institute of Biomedical ScienceThe Institute of Biomedical Science (IBMS) is the professional body for biomedical scientists in the United Kingdom. The institute was founded in 1912 and aims to promote biomedical science and its practitioners. There are approximately 20,000 members. The main roles of the IBMS include setting standards of practice to protect patients, assessing competence for biomedical scientists to practise, accrediting university degrees, providing postgraduate professional qualifications, and organizing a continuing professional development (CPD) scheme. Additionally the Institute plays a key role in as-sessing qualifications for registration with the Health and Care Professions Council (HCPC).

The IBMS holds a biennial conference and publishes monthly The Biomedical Scientist which con-tains science articles, news, and job adverts. The Institute’s scientific publication is the British Journal of Biomedical Science containing peer-reviewed scientific papers. It is not mandatory for biomedical scientists to be members of the IBMS, but there are many benefits, including the authority to adopt designatory initials that indicate the class of membership, such as MIBMS (member) or FIBMS (fellow). (See also Box 1.5.)

The IBMS website gives full details. http://www.ibms.org

1.4.2 The British Society for HaematologyThe British Society for Haematology (BSH) is the main haematology society in the UK; its main objec-tive is to advance the study and practice of haematology. The BSH provides education, information, and networking to haematologists. The Society holds an annual scientific meeting and publishes the peer-reviewed journal British Journal of Haematology.

A major role of the BSH is to publish guidelines from the British Committee for Standards in Haematology. For full information about the BSH see http://www.b-s-h.org.uk

The material learnt during your undergraduate degree that qualifies you to enter the profes-sion will not provide you with all the knowledge you need for your entire career. Medicine, biomedical science, and technology progress at a rapid pace and it is a requirement that health professionals constantly strive to maintain and update their knowledge and profes-sional practice. The IBMS has a mature scheme that allocates credits for a range of profes-sional and educational activities. If a practitioner accrues sufficient credits within a specified time period they are awarded a CPD Diploma.

CPD activities must be varied in nature to update different areas of practice. Suitable CPD activities include attending conferences and lectures, learning new laboratory procedures/techniques, reading up-to-date research articles, attending journal clubs, giving lectures/tu-torials, publishing scientific papers, and writing reflective statements on workplace learning. The IBMS publishes monthly journal-based learning ( JBL) exercises where practitioners read a relevant article and then answer questions that have been set by IBMS examiners. Pass marks in JBL attract additional CPD points.

BOX 1.5 Continuing professional developmentPrev

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1.4.3 Health and Care Professions CouncilIt is mandatory that all healthcare scientists practising in the NHS in the UK are registered with the HCPC. The HCPC is the regulator and exists to protect the public. Practitioners have to reach specific standards of education and professional competence to gain entry onto the register and attain the status of a registered healthcare professional. All healthcare professionals are required to continue to keep their knowledge and skills up to date while they are registered and practising in their profes-sion. At re-registration a percentage of individuals are selected at random for audit, whereby they are expected to provide a summary of practice for the previous two years, evidence of varied CPD activi-ties, and a statement with evidence that demonstrates how they have met the standards. The HCPC website gives full details: http://www.hpc-uk.org

1.4.4 Chartered Scientist (CSci)CSci represents a single chartered mark for all scientists, recognizing high levels of professionalism and competence in science. Being chartered is the mark of professional recognition, and being a Chartered Scientist allows all scientists working at the full professional level to be recognized on an equal footing. It gives an assurance of current competence through mandatory revalidation, and encapsulates the interdisciplinary nature of science in the twenty-first century. By benchmarking professional scientists at the same high level, CSci aims to re-engage public trust and confidence in science and scientists.

All those working in the practice, application, advancement or teaching of science can become CSci with the appropriate combination of qualifications and experience. Chartered Scientists work in an ever-growing diversity of settings, from food science to nuclear physics, and mathematical modelling to chemical engineering.

In order to be awarded CSci status, applicants must demonstrate various competencies includ-ing the ability to deal with complex issues and communicate their conclusions to a range of audi-ences. They must show originality in problem solving and substantial autonomy in planning and implementing tasks. Through a commitment to continuing professional development, Chartered Scientists will continue to advance their knowledge, understanding and competence throughout their career.

Practitioners seeking CSci status are advised to contact the IBMS.

SELF-CHECK 1.6

What are the major roles of the professional body?

SELF-CHECK 1.7

Why is CPD important to effective professional practice as a biomedical scientist?

Chapter summary

■ Haematology is the study of diseases of the blood and blood-forming organs.

■ The biomedical scientist in haematology performs analyses that assist in the differential diagnosis and management of disease.

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1 INTRODUCTION TO HAEMATOLOGY 15

■ Haematology inevitably overlaps with other physiologies and disciplines within pathology.

■ The roles of the various professional bodies include setting professional, scientific, educational, and quality control standards.

Discussion questions

1.1 Why is haematology considered a discrete discipline when the white cell aspects could be part of the immunology discipline, and the measurement of certain molecules and elements could be contained within biochemistry?

1.2 What effect would the loss of a haematology service have on healthcare delivery in a hospital?

Answers to self-check questions and case study questions are provided in the book’s Online Resource Centre.

Visit www.oxfordtextbooks.co.uk/orc/moore2e

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