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Herausgeber: John Wiley & Sons
Kategorie: Fachliteratur
Sprache: Englisch

Beschreibung

The latest edition of the key haematology text

Haematology, the study and treatment of blood and bone marrow disorders, is a rich and complex discipline that consistently produces cutting-edge medical research. Since 1972, Hoffbrand’s Postgraduate Haematology has acted as the foundational overview and reference text for this subject, introducing generations of trainees and medical residents to the pathogenesis, clinical and laboratory features, and management of blood disorders.

The eighth edition of Hoffbrand’s Postgraduate Haematology, now with a new editorial team including leading clinicians and researchers, promises to continue this tradition of excellence with a fully updated text. Lavishly illustrated, comprehensive, and thoughtfully referenced, it is an indispensable resource.

Readers of the eighth edition of Hoffbrand’s Postgraduate Haematology will also find:

Four-color illustrations and photomicrographs of blood cells and tissues throughout to support key topics
New sections analysing recent advances in next generation sequencing, genome editing, clonal haematopoiesis, anticoagulant drugs, diagnostic laboratory tools, and more
Companion website with downloadable figures and other tools

Hoffbrand’s Postgraduate Haematology is ideal for all postgraduate trainees or residents in haematology, as well as for clinicians and practitioners looking for a reference work on the subject and a guide to the latest research.

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Leseprobe

Cover

Table of Contents

Title Page

About the editors

Contributor’s list

Preface to the eighth edition by Adam J Mead

Preface to the eighth edition by A Victor Hoffbrand

Preface to the first edition

About the companion website

PART I: General principles of haematology

CHAPTER 1: Human stem cells and haemopoiesis

Introduction

Human haemopoietic stem cells and the haemopoietic differentiation hierarchy

Human haemopoietic stem cell characteristics

Assays for human haemopoiesis

Identification of human haemopoietic stem cells

Development of haemopoietic stem cells

Regulation of haemopoietic stem cells

Fate‐mapping human haemopoiesis

Clinical relevance of haemopoietic stem cells

Selected bibliography

CHAPTER 2: Phagocytes

Introduction

The phagocyte lineage at a glance

Phagocyte identification and quantification

General phagocyte molecules and functions

Phagocyte particulars

Disorders of the phagocyte system

Conclusion

Acknowledgements

Selected bibliography

CHAPTER 3: Erythropoiesis in the human

Introduction

The developmental origins of erythropoiesis

The cellular and molecular pathways leading to definitive erythropoiesis

Differentiation and terminal maturation

Changes in the expression of key erythroid proteins during terminal differentiation

The erythroid niche

The regulation of erythropoiesis by cytokines and cell signalling

The regulation of apoptosis in erythropoiesis

The coordination of erythropoiesis and iron metabolism

The control of erythropoiesis via the oxygen‐sensing system

The mature red cell, senescence and clearance

Assessing erythropoiesis

Concluding remarks

Selected bibliography

CHAPTER 4: Lymphocyte development and function

Introduction

B cells

Antibodies

Antibody function

Fc‐Fc receptor‐mediated interactions

Complement fixation

Neutralising activity

The B cell receptor

T cells

Antigen recognition by the TCR

CD4

and CD8

T cells and their functions

Differentiation of primed T cells into effector cells

Regulatory CD4

T cells

The role of co‐stimulatory and inhibitory molecules

Natural killer cells

Natural killer T cells

The immune response in cancer and its therapy

Interpretation of blood lymphocyte counts

Selected bibliography

CHAPTER 5: The spleen

Structure and function of the spleen

Splenic blood flow and the red pulp

Blood pooling within the spleen

Role of the spleen in ensuring quality control of red cells

Immunological function of the spleen

Splenomegaly and hypersplenism

Non‐Hodgkin lymphoma

Hodgkin lymphoma

Myeloid stem cell disorders

Patient education

Vaccination

Antibiotics

Hyposplenism

Selected bibliography

CHAPTER 6: Cancer immunotherapy

Introduction

Immune evasion and subversion in cancer

Types of immunotherapy

Future of immunotherapy

Selected bibliography

CHAPTER 7: Clinical applications of gene editing and therapy

Introduction

General principles of gene therapy

Gene therapy in haemopoietic stem cells

Gene therapy for haemophilia

Delivery of genome editing technology

Genome editing for the β‐thalassaemias and sickle cell disease

Safety of genome editing

Conclusion

Selected bibliography

CHAPTER 8: Application of next‐generation sequencing in haematology

Introduction

NGS technology

Bioinformatic processing and interpretation of data

Utility

Practical considerations

The future

Selected bibliography

CHAPTER 9: The molecular basis of haematological malignancies

Introduction

The cancer genome

Classes of DNA mutations

Inherited predisposition to haematological cancers

Clonal evolution and subclonal architecture of haematological cancers

Selected bibliography

CHAPTER 10: Laboratory diagnosis of haematological neoplasms

Introduction

Blood count and blood film

Bone marrow aspirate

Bone marrow trephine biopsy

Cytochemistry

Histology

Flow cytometric immunophenotyping

Immunohistochemistry

Cytogenetic analysis

Fluorescence

in situ

hybridisation

Molecular genetic analysis

Whole‐genome scanning

Microarray analysis of gene expression

Next‐generation sequencing

Laboratory techniques and the WHO classification of tumours of haemopoietic and lymphoid tissues

Conclusions

Selected bibliography

PART II: Red blood cell disorders and blood transfusion

CHAPTER 11: Iron metabolism, iron deficiency and disorders of haem synthesis

Introduction

Distribution of body iron

Proteins important in iron metabolism

Normal iron balance

Diagnostic methods for investigating iron metabolism

Iron deficiency

Management of iron deficiency

Pathological alterations in haem synthesis

Sideroblastic anaemia

Selected bibliography

CHAPTER 12: Iron overload

Introduction

Hereditary haemochromatosis

Rare genetic causes of iron overload associated with anaemia

Iron‐loading anaemias

Tests of body iron burden

Iron chelation therapy

Selected bibliography

CHAPTER 13: Megaloblastic anaemia

Introduction

Underlying basic science

Clinical features

Haematological findings

Cobalamin

Folate

Causes of folate deficiency

Excess utilisation or loss

Diagnosis of folate deficiency

Serum homocysteine

Other nutritional anaemias

Selected bibliography

CHAPTER 14: Haemoglobin and the inherited disorders of globin synthesis

Introduction

The structure, genetic control and synthesis of haemoglobin

Classification of the disorders of haemoglobin

The thalassaemias and related disorders

The β‐thalassaemias

The α‐Thalassaemias

Thalassaemia intermedia (non‐transfusion‐dependent thalassaemia)

Structural haemoglobin variants related to thalassaemia

Acknowledgement

Selected bibliography

CHAPTER 15: Sickle cell disease

Introduction

Geographic distribution of sickle mutation

Pathophysiology

Clinical manifestations

Variant sickle cell syndromes

Diagnosis

Therapy

Selected bibliography

CHAPTER 16: Hereditary disorders of the red cell membrane and disorders of red cell metabolism

Haemolysis

Red cell membrane disorders

Defects of red cell metabolism

Selected bibliography

CHAPTER 17: Acquired haemolytic anaemias

Introduction

Immune haemolytic anaemias

Clinical features of warm AIHA

Clinical management

Cold agglutinin disease

Paroxysmal cold haemoglobinuria (PCH)

Alloimmune haemolytic anaemia with anti‐D

Non‐immune acquired haemolytic anaemias

Selected bibliography

CHAPTER 18: Red cell immunohaematology

Introduction

Blood group systems

The red cell membrane and chemistry of blood group antigens

Blood group antibodies

Clinical significance of red cell antibodies

Detection of red cell antigen–antibody reactions

Molecular techniques for blood grouping

The ABO system

The Lewis system

P1, P

and P blood group antigens and antibodies

I and i antigens and antibodies

The Rh system

The MNS system

The Kell blood group system

Other blood group systems

Polyagglutinable red cells

The biological significance of blood group antigens

Selected bibliography

CHAPTER 19: Clinical blood transfusion

Introduction

Blood transfusion and regulatory aspects

The blood donor

Selection criteria and blood donation

Transfusion‐transmitted infection (TTI)

Laboratory tests on blood donations

Storage and processing of blood

Blood components

Clinical and laboratory transfusion practice

Laboratory tests in patients

Special requirements for the selection of blood

Safe administration of blood

Complications of blood transfusion

Haemovigilance

Appropriate use of blood and alternatives to allogeneic blood transfusion

Haemolytic disease of the foetus and newborn (HDFN)

Selected bibliography

PART III: Lymphoid disorders

CHAPTER 20: The classification of lymphomas

Introduction

Mature B‐cell neoplasms

Mature NK‐cell/T‐cell neoplasms

Hodgkin lymphoma

Selected bibliography

CHAPTER 21: Adult acute lymphoblastic leukaemia

Introduction

Diagnosis of adult ALL

Genetics

Initial approach to a patient with ALL

Specific approaches to defined clinical populations in the treatment of ALL

Selected bibliography

CHAPTER 22: Childhood acute lymphoblastic leukaemia

Introduction

Epidemiology

Aetiology

Pathogenesis

Clinical features

Differential diagnosis

Laboratory features

Immunophenotypic classification

Cytogenetic and molecular classification

Prognostic factors

Treatment

Treatment of distinct subgroups

Relapse

Early and late toxicity

Treatment in a resource poor setting

Future strategies and conclusions

Acknowledgements

Selected bibliography

CHAPTER 23: Chronic lymphocytic leukaemia and other chronic B‐cell lymphoproliferative disorders

Classification

General aspects of diagnostic methodology

Chronic lymphocytic leukaemia

Monoclonal B‐cell lymphocytosis

Management of symptomatic disease

Other B‐cell chronic disorders with leukaemic expression

Hairy‐cell leukaemia

Non‐nodal, leukaemic mantle cell lymphoma

Follicular lymphoma

Splenic B‐cell lymphoma/leukaemia with prominent nucleoli (Hairy‐cell leukaemia variant)

Splenic diffuse red pulp small B‐cell lymphoma

Acknowledgements

Selected bibliography

CHAPTER 24: T‐cell lymphoma and lymphoproliferative disorders

Introduction

Chronic T‐cell leukaemias

Nodal peripheral T‐cell non‐Hodgkin lymphomas

Extranodal peripheral T‐cell non‐Hodgkin lymphomas

Treatment of peripheral T‐cell non‐Hodgkin lymphomas

Cutaneous T‐cell non‐Hodgkin lymphomas

Conclusions

Acknowledgements

Selected bibliography

CHAPTER 25: Hodgkin lymphoma

Introduction

Pathological features

Pathogenesis

Clinical features

Investigations

Principles of Hodgkin lymphoma treatment

Frontline treatment

Relapsed and refractory disease

Late effects and survivorship

Conclusion

Selected bibliography

CHAPTER 26: Indolent non‐Hodgkin lymphomas

Introduction

Follicular lymphoma

Pathogenesis of FL

Clinical and pathological features of FL

Staging and baseline investigations in FL

Prognostic markers in FL

Management of early‐stage FL

Management of asymptomatic low tumour burden advanced‐stage FL

Management of symptomatic high tumour burden advanced‐stage FL

Induction therapy

Maintenance and consolidation therapy after induction

Management of relapsed FL

Transplantation in relapsed FL

Novel therapies for FL

Management of transformed FL

Marginal zone lymphomas

First‐line systemic therapy for MZL

MALT lymphoma

Gastric MALT

Non‐gastric MALT lymphoma

Splenic marginal zone lymphoma

Nodal marginal zone lymphoma

First‐line systemic therapy for symptomatic advanced‐stage MZL

Management of relapsed MZL

Waldenström macroglobulinaemia

Management of Waldenström macroglobulinaemia

Stem cell transplantation for Waldenström macroglobulinaemia

Selected bibliography

CHAPTER 27: Aggressive B‐cell non‐Hodgkin lymphoma

Introduction

Epidemiology

Classification of aggressive B‐cell lymphomas

Aetiology

Diagnosis

Clinical features

Laboratory investigations

Staging

Treatment

Particular considerations prior to therapy

Diffuse large B‐cell lymphoma

High‐grade B‐cell lymphoma with MYC and

BCL2

rearrangements (Double‐hit lymphoma)

Primary mediastinal (thymic) large B‐cell lymphoma

Primary central nervous system lymphoma

Burkitt lymphoma

Post‐transplant lymphoproliferative disorder

Other rare aggressive B‐cell lymphoma subtypes

Future directions

Selected bibliography

CHAPTER 28: Multiple myeloma

Epidemiology and aetiology

Pathogenesis

Differential diagnosis

Other special forms of plasma cell dyscrasia

Disease complications and their management

Prognostic factors

Treatment

Acknowledgements

Selected bibliography

CHAPTER 29: Amyloidosis

Introduction

Pathogenesis of amyloid

Systemic AL amyloidosis

Localised AL amyloidosis

Other forms of systemic amyloidosis

Conclusion and future directions

Selected bibliography

PART IV: Stem cell and myeloid disorders

CHAPTER 30: Inherited aplastic anaemia/bone marrow failure syndromes

Introduction

Fanconi anaemia

Dyskeratosis congenita

Shwachman–Diamond syndrome

Diamond–Blackfan anaemia (DBA)

Congenital dyserythropoietic anaemia

Thrombocytopenia with absent radii (TAR)

Congenital amegakaryocytic thrombocytopenia (CAMT)

Conclusion

Acknowledgements

Selected bibliography

CHAPTER 31: Acquired aplastic anaemia and paroxysmal nocturnal haemoglobinuria

Acquired aplastic anaemia

Immunosuppressive therapy

Allogeneic HSCT

Paroxysmal nocturnal haemoglobinuria

Efficacy of eculizumab

List of Tables

Chapter 2

Table 2.1 Selected opsonic and non‐opsonic receptors of phagocytes.

Table 2.2 Phagocyte adhesion molecules.

Table 2.3 Examples of Chemotactic factors controlling phagocytes.

Table 2.4 Neutrophil microbicidal proteins.

Table 2.5 Neutrophil granules and their contents.

Table 2.6 Contents of eosinophil granules.

Table 2.7 Biologic activities of selected Eosinophil granule proteins.

Table 2.8 Basophil and mast cell granules and their contents.

Table 2.9 Inherited neutrophil disorders.

Table 2.10 Monogenic autoinflammatory syndromes.

Table 2.11 Monogenetic interferonopathies.

Chapter 4

Table 4.1 Normal ranges for lymphocyte subsets in the blood.

Table 4.2 Non‐malignant causes of lymphocytosis.

Chapter 5

Table 5.1 Causes of splenomegaly.

Table 5.2 Suggested schedule for vaccine immunisation in individuals with as...

Table 5.3 Causes of hyposplenism.

Chapter 8

Table 8.1 Comparison of advantages and disadvantages of hybridsation‐based v...

Table 8.2 List of gene panels (with 3 or more target genes) currently commis...

Table 8.3 Gives illustrative examples of where NGS is used in clinical pract...

Chapter 9

Table 9.1 Glossary.

Table 9.2 Examples of risk factors for the development of leukaemia and lymp...

Chapter 10

Table 10.1 The 2022 WHO classification of acute myeloid leukaemia (AML).

Table 10.2 The WHO 2022 classification of acute lymphoblastic leukaemia (see...

Table 10.3 Cytogenetic/molecular genetic abnormalities that were incorporate...

Chapter 11

Table 11.1 Iron transport proteins, oxidoreductases, storage proteins and re...

Table 11.2 Daily iron losses and requirements.

Table 11.3 Differential diagnosis of hypochromic anaemia.

Table 11.4 Causes of absolute iron deficiency.

Table 11.5 Causes of functional iron deficiency, anaemia of inflammation or ...

Table 11.6 Human porphyrias.

Table 11.7 Classification of sideroblastic anaemias.

Chapter 12

Table 12.1 Causes of iron overload.

Table 12.2 Classification of hereditary haemochromatosis.

Table 12.3 Characteristics of desferrioxamine, deferiprone and deferasirox....

Table 12.4 Monitoring for iron‐induced organ damage.

Chapter 13

Table 13.1 Causes of megaloblastic anaemia.

Table 13.2 Biochemical reactions of folate co‐enzymes.

Table 13.3 Conditions in which macrocytosis or hypersegmented neutrophils ma...

Table 13.4 Causes of cobalamin deficiency causing megaloblastic anaemia.

Table 13.5 Malabsorption of cobalamin may occur in the following conditions ...

Table 13.6 Causes of folate deficiency.

Chapter 14

Table 14.1 The thalassaemias and related disorders.

Table 14.2 Molecular basis of β‐thalassaemias intermedia.

Table 14.3 Diseases due to structural haemoglobin variants.

Chapter 15

Table 15.1 The sickling syndromes.

Table 15.2 Areas of high prevalence of sickle mutation.

Table 15.3 Presenting symptoms of acute chest syndrome.

Table 15.4 Summary of disease‐modifying therapies currently available.

Table 15.5 Advances in the management of sickle cell disease.

Chapter 16

Table 16.1 Main features of haemolytic anaemia.

Table 16.2 Proteins of the red cell membrane.

Table 16.3 Guidelines for prevention and management of infection in the sple...

Table 16.4 Features of hereditary stomatocytosis and related disorders.

Table 16.5 Molecular basis of hereditary stomatocytosis and related disorder...

Table 16.6 Main features of red cell enzyme deficiencies.

Table 16.7 World Health Organisation classification of G6PD deficiency (1989...

Table 16.8 Characteristic features of haemolytic attack in G6PD deficiency....

Table 16.9 Drugs to be avoided in G6PD deficiency.

Chapter 17

Table 17.1 Classification of immune haemolytic anaemias.

Table 17.2 Drug‐induced immune haemolytic anaemias: clinical and serological...

Table 17.3 Serological characteristics of cold‐acting antibodies in the cold...

Table 17.4 Non‐immune acquired haemolytic anaemias.

Table 17.5 Classification of anaemias caused by fragmentation haemolysis.

Table 17.6 Causes of microangiopathic haemolytic anaemia.

Table 17.7 Substances causing oxidative haemolysis and/or methaemoglobinaemi...

Chapter 18

Table 18.1 Human blood group systems.

Table 18.2 Incidence of ABO groups in the UK.

Table 18.3 ABO blood grouping.

Table 18.4 The Lewis system and secretion of ABH.

Table 18.5 Eight Rh haplotypes and their frequencies in English, Nigerian an...

Chapter 19

Table 19.1 Measures to protect the donor from adverse effects of large‐volum...

Table 19.2 Transfusion‐transmissible agents.

Table 19.3 Microbial testing in England.

Table 19.4 Measures to protect the recipient.

Table 19.5 Specifications of red cells for foetal/neonatal/infant transfusio...

Table 19.6 Indications for irradiated cellular blood components

in haem...

Table 19.7 Selection of ABO blood group of components transfused in the earl...

Table 19.8 Hazards of transfusion.

Table 19.9 Antibodies associated with haemolytic transfusion reactions.

Table 19.10 Investigation of suspected acute haemolytic transfusion reaction...

Table 19.11 Comparison of transfusion‐related acute lung injury (TRALI) and ...

Table 19.12 TACO classification criteria.

Table 19.13 Preoperative assessment of patients.

Table 19.14 Potentially sensitising events in pregnancy.

Chapter 20

Table 20.1a International consensus classification of mature lymphoid neopla...

Table 20.1b WHO‐5 edition classification of mature lymphoid neoplasms.

Table 20.2 Immunophenotypic features of common B‐cell neoplasms.

Table 20.3 Plasma cell neoplasms.

Table 20.4 Genetic subgroups of DLBCL.

Source:

Table 20.5 Immunophenotypic features of common T‐cell neoplasms.

Chapter 21

Table 21.1 WHO classification of ALL.

Table 21.2 Comparison of MRD assays in ALL.

Table 21.3 Factors commonly used to predict outcome or stratify therapy.

Table 21.4 Suggested checklist for the initial assessment of an adult patien...

Chapter 22

Table 22.1 Characteristics and 10‐year survival rates for 3113 patients in U...

Table 22.2 Drugs used in the treatment of childhood ALL.

Table 22.3 Outcomes with contemporary childhood ALL protocols.

Table 22.4 UKALL 2003 serious adverse events.

Chapter 23

Table 23.1 B‐cell chronic lymphoproliferative disorders with leukaemic expre...

Table 23.2 Immunophenotypic and genetic markers in chronic B‐cell lymphoprol...

Table 23.3 Cytogenetic and molecular features. Biologic and clinical correla...

Table 23.4 Comparison of CLL, SLL and MBL.

Table 23.5 Rai and Binet clinical stages.

Table 23.6

IGHV

gene mutational status: biological and clinical correlates....

Table 23.7 Prognostic biomarkers.

Table 23.8 Biomarkers associated with disease progression in asymptomatic Bi...

Table 23.9 Biomarkers predicting response to therapy. Differences between ch...

Table 23.10 Representative clinical trials in CLL.

Chapter 24

Table 24.1 The 2022 World Health Organisation (WHO) classification of mature...

Table 24.2 Requirements to establish the diagnosis of T‐PLL.

Table 24.3 World Health Organization/European Organisation for Research and ...

Table 24.4 Description of TNM‐B staging system categories for mycosis fungoi...

Table 24.5 TNM‐B staging system for mycosis fungoides.

Table 24.6 Morphologic and immunophenotypic classification of lymphomatous p...

Chapter 25

Table 25.1 Ann Arbor staging system with Cotswolds modifications.

Table 25.2 Different definitions of early‐stage favourable and unfavourable ...

Table 25.3 Outcomes in patients with advanced‐stage classical Hodgkin lympho...

Table 25.4 Deauville score for the standardised reporting of PET scans in ly...

Table 25.5 Outcomes of selected trials in early‐stage and advanced‐stage cla...

Chapter 26

Table 26.1 Outcomes according to risk group defined by the FLIPI, FLIPI2 and...

Table 26.2 Summary of results of key trials randomised trials of first‐line ...

Table 26.3 Suggested algorithm for management of FL.

Table 26.4 Summary of results of key trials of immunotherapy and immunochemo...

Table 26.5 Risk stratification in Waldenström macroglobulinaemia according t...

Table 26.6 Guidelines for management of Waldenström macroglobulinaemia.

Chapter 27

Table 27.1 Classification of aggressive, mature B‐cell lymphomas in accordan...

Table 27.2 Clinical prognostic scoring systems in patients with DLBCL.

Table 27.3 Selected key phase III trials in first‐line DLBCL.

Table 27.4 Chemotherapy protocols used in high‐grade NHL.

Table 27.5 Central nervous system international prognostic index.

Chapter 28

Table 28.1 Prognostic value of the main chromosomal abnormalities of multipl...

Table 28.2 Types of monoclonal gammopathy of undetermined significance.

Table 28.3 Myeloma‐related organ or tissue impairment (end‐organ damage) due...

Table 28.4 Diagnostic criteria for Multiple myeloma. Clonal bone marrow plas...

Table 28.5 Work‐up for a patient with monoclonal gammopathy.

Table 28.6 Prognostic factors in MM.

Table 28.7 IMWG Standard and MRD response criteria.

Chapter 29

Table 29.1 Classification of amyloidosis (by clinical frequency).

Table 29.2 Non‐invasive diagnostic criteria for amyloid‐related major organ ...

Chapter 30

Table 30.1 The inherited BMF syndromes.

Table 30.2 Characteristics of the BMF syndromes.

Table 30.3 Somatic abnormalities in FA.

Table 30.4 FA complementation groups/genetic subtypes.

Table 30.5 Somatic abnormalities in dyskeratosis congenita.

Table 30.6 Genetic subtypes of dyskeratosis congenita.

Table 30.7 Genetic subtypes of Shwachman–Diamond syndrome.

Table 30.8 Genetic subtypes of Diamond–Blackfan anaemia.

Table 30.9 Characteristics of common subtypes of congenital dyserythropoieti...

Table 30.10 Genetic subtypes of neutropenia.

Table 30.11 Genetic subtypes of syndromic thrombocytopenias.

Table 30.12 New BMF and overlapping syndromes.

Table 30.13 Laboratory tests useful in the investigation of patients with BM...

Chapter 31

Table 31.1 Laboratory assessment of a newly presenting patient.

Table 31.2 Direct comparisons of horse and rabbit ATG with CSA as first‐line...

Table 31.3 Outcomes of HLA‐matched sibling donor HSCT from recent studies us...

Table 31.4 Sites of thrombotic events in haemolytic PNH.

Chapter 32

Table 32.1 Commoner germline predisposition to AML.

Table 32.2 ICC classification of AML and related neoplasms.

Table 32.3 Diagnostic workup of AML.

Table 32.4 2022 ELN AML risk stratification by genetics.

Chapter 33

Table 33.1 Definition of advanced phase CML disease.

Table 33.2 Consensus time‐dependent molecular targets from the US National C...

Table 33.3 Summary of representative treatment‐free remission studies in the...

Table 33.4 Consensus ELN 2020 criteria for treatment free remission (TFR) at...

Chapter 34

Table 34.1 The WHO 2016 classification of MDS and MDS/MPN.

Table 34.2 Germline mutations predisposing to myeloid neoplasms. Within each...

Table 34.3 Somatic mutations in MDS and MDS/MPN. Colour code represent the p...

Table 34.4 Differential diagnoses to MDS and MDS/MPN.

Table 34.5 IPSS‐R prognostic score for MDS.

Table 34.6 CPSS molecular risk score for CMML.

Chapter 35

Table 35.1 Causes of an erythrocytosis.

Table 35.2 Diagnostic criteria for polycythaemia vera.

Table 35.3 Causes of thrombocytosis.

Table 35.4 Diagnostic criteria for essential thrombocythaemia proposed by th...

Table 35.5 Revised IPSET‐thrombosis risk stratification system.

Table 35.6 Criteria for high‐risk pregnancy in myeloproliferative neoplasms ...

Table 35.7 Diagnostic criteria of prefibrotic myelofibrosis.

Table 35.8 Diagnostic criteria for PMF.

Table 35.9 Diagnostic criteria for post PV or post ET MF.

Table 35.10 Differential diagnosis of marrow fibrosis.

Table 35.11 Risk stratification for PMF patients.

Table 35.12 Newer prognostic models in primary myelofibrosis incorporating n...

Table 35.13 A specific prognostic model for myelofibrosis secondary to PV an...

Table 35.14 Treatment options for myelofibrosis according to clinical need....

Table 35.15 World Health Organization (WHO 2022) classification and criteria...

Table 35.16 Suggested evaluation of a patient with persistent eosinophilia, ...

Table 35.17 Diagnostic criteria for chronic neutrophilic leukaemia from the ...

Chapter 36

Table 36.1 Classification of the histiocytic disorders.

Table 36.2 Comparison of HLH criteria.

Chapter 37

Table 37.1 Acute GVHD scoring – MAGIC criteria (a) clinical staging; (b) cli...

Table 37.2 Causes of abnormal liver function tests after allogeneic SCT.

Table 37.3 Immediate complications of autologous SCT.

Table 37.4 Indications for SCT.

Chapter 38

Table 38.1 Definitions of CH and related terms.

Chapter 39

Table 39.1 Key proteins involved in the haemostatic network.

Chapter 40

Table 40.1 Platelet α‐granule constituents. Examples of platelet α‐granule c...

Chapter 41

Table 41.1 Haemophilia A

: clinical severity.

Table 41.2 Indications and guidelines for factor replacement in haemophilia ...

Table 41.3 Mutations responsible for haemophilia A.

Table 41.4 Assays or von Willebrand factor.

Table 41.5 Classification of von Willebrand disease.

Table 41.6 Disorders associated with acquired von Willebrand syndrome and me...

Chapter 42

Table 42.1 General features of autosomal recessive deficiency of coagulation...

Table 42.2 General recommendations for treatment and long‐term prophylaxis i...

Chapter 43

Table 43.1 Clinical conditions associated with disseminated intravascular co...

Table 43.2 Differential diagnosis of disseminated intravascular coagulation ...

Table 43.3 ISTH Sub‐Committee of the Scientific and Standardisation Committe...

Table 43.4 Features of vitamin K deficiency bleeding (VKDB).

Table 43.5 Causes of increased bleeding tendency or coagulation abnormalitie...

Table 43.6 Platelet abnormalities reported in uraemia.

Table 43.7 Guide to blood product replacement in massive blood loss.

Table 43.8 Bleeding symptoms in patients with acquired haemophilia A

....

Table 43.9 Diseases associated with acquired haemophilia A.

Chapter 44

Table 44.1 Main specific clinical differences between diseases of coagulatio...

Table 44.2 Classification of congenital platelet disorders.

Table 44.3 Main clinical differences amongst syndromes due to pathogenic var...

Table 44.4 Platelet response to aggregating agents in different thrombocytop...

Table 44.5 Genes involved in congenital platelet disorders.

Chapter 45

Table 45.1 Consensus Terminology definitions.

Table 45.2 Potential causes of thrombocytopenia in ITP.

Table 45.3 Investigation of suspected ITP.

Table 45.4 Indications for bone marrow examination in ITP.

Table 45.5 Treatment options after first‐line therapy.

Table 45.6 Target platelet counts for procedures.

Table 45.7 Causes of maternal thrombocytopenia in pregnancy.

Table 45.8 Investigation of suspected ITP in pregnancy.

Chapter 46

Table 46.1 Underlying conditions and diseases associated with immune‐mediate...

Table 46.2 Presenting clinical symptoms and signs in acute TTP.

Table 46.3 Clinical applications of

ADAMTS13

testing in acute TTP and aHUS....

Table 46.4 Clinical conditions presenting as thrombotic microangiopathies (T...

Table 46.5 Components of the PLASMIC score.

Table 46.6 Steps in the acute management of acquired, immune mediated TTP.

Table 46.7 Main complement factors and regulators with their function and fr...

Chapter 47

Table 47.1 Features of GPIIb/IIIa antagonists.

Table 47.2 Comparison of heparin, Lmwh and fondaparinux.

Table 47.3 Features of heparin‐induced thrombocytopenia.

Table 47.4 Management of heparin‐induced thrombocytopenia.

Table 47.5 Comparison of the pharmacologic properties of the direct oral ant...

Table 47.6 Reversal agents for direct oral anticoagulants.

Chapter 48

Table 48.1 Risk factors for venous thromboembolism.

Table 48.2 Diagnostic criteria in APS.

Table 48.3 Effects of inflammation on haemostasis.

Chapter 49

Table 49.1 Table of additional VTE risk factors and bleeding risk factors, b...

Table 49.2 Padua VTE risk assessment model (high risk of VTE: ≥4).

Table 49.3 Wells clinical score used for predicting the probability of DVT p...

Table 49.4 Wells clinical score used for predicting the probability of PE pr...

Table 49.5 Stratifying pulmonary embolism by risk of death.

Table 49.6 Suggested duration of anticoagulation.

Chapter 50

Table 50.1 Risk scores to estimate risk of ischaemic stroke and bleeding res...

Chapter 51

Table 51.1 Automated white cell (WBC) and neutrophil counts in adults of dif...

Table 51.2 Clinical features of

P. falciparum

malaria infection.

Table 51.3 Differentiating epidemiological and stained thin blood film featu...

Chapter 52

Table 52.1 Haematological presentations of Lysosomal storage disorders.

Table 52.2 Examples of differential diagnosis of lipid‐laden macrophages, ps...

Table 52.3 Clinical manifestations of Gaucher disease.

Chapter 53

Table 53.1 Classification and haematological parameters of thalassaemia.

Table 53.2 Stratification of maternal bleeding risk in inherited bleeding di...

Table 53.3 Stratification of Neonatal bleeding risk in Inherited Bleeding di...

Chapter 54

Table 54.1 Composition of haemoglobins in the human embryo, fetus and neonat...

Table 54.2 Common of neonatal anaemia.

Table 54.3 Causes of neonatal polycythaemia.

Table 54.4 Causes of neonatal thrombocytopenia.

Chapter 55

Table 55.1 Summary of blood product transfusion in patients with acute leuka...

Table 55.2 Important pathogens in leukaemia patients.

Table 55.3 Locations of access for endogenous bacteria frequently causing in...

Table 55.4 Mechanisms of resistance and important considerations flowing the...

Table 55.5 ECIL recommendations for allo‐HSCT recipients.

Chapter 56

Table 56.1 Causes of reduced red cell production in patients with cancer.

Table 56.2 Causes of increased red cell destruction in patients with cancer....

Table 56.3 Leucocyte changes associated with malignancy.

Table 56.4 Causes of thrombocytopenia in patients with malignancy.

Table 56.5 Causes of anaemia in acute renal impairment.

Table 56.6 Causes of anaemia in chronic renal impairment.

Table 56.7 Platelets and liver disease.

Table 56.8 Causes of anaemia in liver disease.

Table 56.9 Anaemia in connective tissue disorders.

Table 56.10 Haematological consequences of endocrine disease.

Table 56.11 Mechanisms of development of cytopenia in patients with HIV.

Table 56.12 Haematological changes in bacterial, fungal and protozoal infect...

Chapter 57

Table 57.1 Trial results for tranexamic acid.

Table 57.2 Factors to consider before re‐initiation of anticoagulation follo...

Table 57.3 Causes of recurrent thrombosis while on therapeutic anticoagulati...

Table 57.4 Settings where bridging doses of heparin might be considered when...

Table 57.5 DOAC perioperative management scheme.

List of Illustrations

Chapter 1

Figure 1.1 The human haemopoietic hierarchy. The human haemopoietic hierarch...

Figure 1.2 Haemopoietic stem cell fate options. Controlling the number of ha...

Figure 1.3 Human haemopoietic stem and progenitor cell assays. (a) Overview ...

Figure 1.4 Genetic fate‐mapping of human haemopoiesis. (a) Overall principle...

Figure 1.5 Clinical use of haemopoietic stem cells. Haemopoietic stem cells ...

Chapter 2

Figure 2.1 Haematopoiesis is controlled by lineage‐determining cytokines and...

Figure 2.2 Morphology of the main phagocytes. (a) PMN or neutrophils appear ...

Figure 2.3 Origin and morphology of the circulating phagocyte family. (a) Sc...

Figure 2.4 Diapedesis and chemotaxis. In inflammation, phagocytes migrate to...

Figure 2.5 Priming and activation of the NLRP3 inflammasome. Phagocytes requ...

Figure 2.6 Components of the NADPH oxidase system. The components include a ...

Figure 2.7 Stages of neutrophil maturation. Stages of neutrophil maturation,...

Figure 2.8 Neutrophil and monocyte swarming. The recruitment of neutrophils ...

Figure 2.9 Neutrophils produce DNA extracellular traps. Representative image...

Figure 2.10 The respiratory burst in eosinophils and neutrophils is assemble...

Figure 2.11 Plasma membrane antigens and receptors expressed by macrophages....

Figure 2.12 Two‐signal macrophage activation model in the context of the imm...

Figure 2.13 Variations in neutrophil morphology. Some nuclear morphologic ch...

Figure 2.14 Type I interferonopathy genotypes according to the function of t...

Chapter 3

Figure 3.1 The three waves of primitive (PE), erythromyeloid (EMP) and defin...

Figure 3.2 The process of erythropoiesis as cells differentiate and mature i...

Figure 3.3 The coordinated synthesis of haem and globin to assemble haemoglo...

Figure 3.4 The erythroid niche. Left is a photomicrograph showing erythroid ...

Figure 3.5 Positive and negative cytokines acting on erythroid cells. (a) po...

Figure 3.6 A negative feedback loop controlling the numbers of mature erythr...

Figure 3.7 Regulation of erythropoiesis and iron metabolism. The major hormo...

Figure 3.8 The oxygen‐sensing system. Under normoxic conditions, HIF‐1α is h...

Figure 3.9 Summary of the regulation of erythropoiesis. Note the key points ...

Chapter 4

Figure 4.1 The key transcription factors and steps in B‐cell development are...

Figure 4.2 Structures of monomeric immunoglobulin molecules are shown. IgA a...

Figure 4.3 The complement cascade comprises three distinct pathways; the cla...

Figure 4.4 (a) BTK and its involvement in BCR signalling. Bruton’s tyrosine ...

Figure 4.5 T cells recognise peptides held in MHC molecules. A class I MHC m...

Figure 4.6 Antigen processing and presentation in association with MHC molec...

Chapter 5

Figure 5.1 The vascular and lymphatic organisation of the spleen. (a) Schema...

Figure 5.2 (a) Computed tomogram showing splenic injury (Organ Injury Scale ...

Figure 5.3 Relative risk of hospital contact for any infection in splenectom...

Figure 5.4 Blood film showing features of hyposplenism: Howell–Jolly bodies,...

Chapter 6

Figure 6.1 Immunotherapeutic approaches to the treatment of cancer. 1. Check...

Figure 6.2 The Solid Tumour Microenvironment (TME) is a highly immunosuppres...

Figure 6.3 Three Signals of T cells activation. 1. Antigen recognition occur...

Figure 6.4 T cell activation: The first signal of T cell activation is TCR e...

Figure 6.5 TIL therapy: 1. Tumour is removed from the patient. 2. TILs are e...

Figure 6.6 Antibody structure: Composed of a light and heavy chain forming t...

Chapter 7

Figure 7.1 General principles of gene therapy and genome editing.

Figure 7.2 Integrating versus non‐integrating viral vectors.

Figure 7.3 General principles of genome editing.

Figure 7.4 Different approaches for using genome editing to treat haemoglobi...

Chapter 8

Figure 8.1 Outline of the workflow for commonly used short and long‐read seq...

Figure 8.2 Outlines the main steps in Amplicon‐based and Hybridization Captu...

Figure 8.3 Flow chart demonstrating the different processing steps raw seque...

Chapter 9

Figure 9.1 The sequence of somatic mutations acquired during cell divisions ...

Figure 9.2 Different types of mutations and chromosomal rearrangements.

Figure 9.3 Common mechanisms of gene activation by chromosomal translocation...

Figure 9.4 Median number of mutations per exome in various haematological an...

Figure 9.5 Schematic representation of NOTCH1 signalling and possible inhibi...

Figure 9.6 Functional consequences of disrupted MLL activity by an MLL fusio...

Figure 9.7 Enzymes involved in DNA methylation whose mutations are implicate...

Figure 9.8 Fusion tyrosine kinases. (a) In normal cells, receptor tyrosine k...

Figure 9.9 The RAS pathway and juvenile myelomonocytic leukaemia (JMML). The...

Figure 9.10 Abnormal splicing in haematological malignancies. (a) In normal ...

Figure 9.11 Linear and branching evolution.

Figure 9.12 Clonal evolution of cancer subclones in relation to treatment.

Chapter 10

Figure 10.1 The principal laboratory methods employed in haematological diag...

Figure 10.2 Burkitt lymphoma showing blast‐like cells with strongly basophil...

Figure 10.3 Blood films of two patients with acute promyelocytic leukaemia: ...

Figure 10.4 Acute hypogranular/microgranular variant of promyelocytic leukae...

Figure 10.5 Chronic lymphocytic leukaemia showing mature small lymphocytes a...

Figure 10.6 MGG‐stained peripheral blood film of chronic myeloid leukaemia (

Figure 10.7 Acute lymphoblastic leukaemia showing blast cells that vary in s...

Figure 10.8 Acute lymphoblastic leukaemia showing medium‐sized and large ple...

Figure 10.9 Acute myeloid leukaemia with minimal differentiation showing lar...

Figure 10.10 Acute myeloid leukaemia without maturation showing small‐ to me...

Figure 10.11 Acute monoblastic leukaemia associated with t(9;11)(p21.3;q23.3...

Figure 10.12 A pseudo‐Pelger–Huët anomaly in a neutrophil of a patient with ...

Figure 10.13 Acute myeloid leukaemia showing leukaemic blast cells, several ...

Figure 10.14 Composite image of myelodysplastic syndrome showing the hypolob...

Figure 10.15 Multiple myeloma (plasma cell myeloma) showing virtual effaceme...

Figure 10.16 Acute myeloid leukaemia (AML) associated with inv(16)(p13.1q22)...

Figure 10.17 Acute myeloid leukaemia (AML) associated with t(16;16)(p13.1;q2...

Figure 10.18 Polycythaemia vera with a

JAK2

V617F mutation showing panmyelos...

Figure 10.19 Acute megakaryoblastic leukaemia (FAB M7 subtype). Bone marrow ...

Figure 10.20 Acute myeloid leukaemia (AML) without maturation showing Auer r...

Figure 10.21 Acute monoblastic leukaemia showing strong reaction for non‐spe...

Figure 10.22 Acute myeloid leukaemia (AML) associated with t(6;9)(p23;q34.1)...

Figure 10.23 Ring sideroblasts and Pappenheimer bodies in erythrocytes in a ...

Figure 10.24 Acute lymphoblastic leukaemia showing block positivity to perio...

Figure 10.25 T‐lineage acute lymphoblastic leukaemia showing focal (Golgi zo...

Figure 10.26 Flow cytometry immunophenotyping showing improvement of separat...

Figure 10.27 A karyogram of Giemsa‐stained chromosomes showing t(9;22)(q34.1...

Figure 10.28 An explanatory diagram (top), karyogram of Giemsa‐stained chrom...

Figure 10.29 Locus‐specific probes for

BCR

(green) and

ABL1

(red) applied to...

Figure 10.30 Diagram showing the principle of fluorescence

in situ

hybridisa...

Figure 10.31 Fluorescence

in situ

hybridisation in four different patients w...

Figure 10.32 Explanatory diagram and fluorescence

in situ

hybridisation show...

Figure 10.33 Metaphase of a patient with acute myeloid leukaemia and a compl...

Figure 10.34 An explanatory diagram and a PCR gel showing the various

BCR::A

...

Figure 10.35

BCR::ABL1

multiplex PCR containing different oligonucleotide (‘...

Figure 10.36 Real‐time quantitative PCR. Fluorescence is plotted against PCR...

Figure 10.37 Molecular karyotype based on high‐density SNP microarray analys...

Chapter 11

Figure 11.1 Iron homeostasis. The major compartments of iron in a 70‐kg man....

Figure 11.2 Stimulatory and inhibitory signals of hepcidin regulation. Hepci...

Figure 11.3 Coordinate regulation of expression of ferritin and transferrin ...

Figure 11.4 Molecular pathways of iron absorption HIF‐2α and hepcidin depend...

Figure 11.5 Incorporation of iron from plasma transferrin into haemoglobin i...

Figure 11.6 (a) A bone marrow showing plentiful iron in macrophages (Perls’ ...

Figure 11.7 Sideroblastic anaemia. Erythroblasts showing perinuclear (mitoch...

Chapter 12

Figure 12.1 Radiograph of hand: patient with haemochromatosis showing loss o...

Figure 12.2 Liver histology (Perls’ stain). (a) Liver biopsy from a patient ...

Figure 12.3 Algorithm for haemochromatosis diagnosis and treatment. The sche...

Figure 12.4 Magnetic resonance imaging T2

technique. Tissue appearances...

Figure 12.5 Relationships of myocardial T2

and left ventricular ejectio...

Chapter 13

Figure 13.1 Role of folate (as 5,10‐methylene‐THF polyglutamate) and methylc...

Figure 13.2 Intracellular cobalamin metabolism. Cbl

, Cbl

and Cbl

refer...

Figure 13.3 The role of folates in DNA synthesis and in formation of

‐adeno...

Figure 13.4 Severe megaloblastic anaemia: (a) peripheral blood(b) bone m...

Figure 13.5 The structure of vitamin B

(cyanocobalamin). There is a corrin...

Figure 13.6 The serum cobalamin‐binding proteins (TCs, transcobalamins). Dar...

Figure 13.7 The structure of folic acid (pteroylglutamic acid) and of a tetr...

Chapter 14

Figure 14.1 (a) The genomic structure of the clusters of α‐like and β‐like g...

Figure 14.2 A prototype globin gene and the genetic control of globin chain ...

Figure 14.3 Heterozygous mutations in the β‐globin gene and the different ph...

Figure 14.4 Deletions causing β‐thalassaemia. The vertical bar indicates the...

Figure 14.5 The pathophysiology of β‐thalassaemia. BM, bone marrow; Epo, ery...

Figure 14.6 The peripheral blood appearances in β‐thalassaemia.

Figure 14.7 Radiograph of a skull of a thalassaemia major patient showing ‘h...

Figure 14.8 The deletions that underlie δβ‐thalassaemia and hereditary persi...

Figure 14.9 The mechanisms for the production of haemoglobin Lepore and rela...

Figure 14.10 The genetics of α‐thalassaemia.

Figure 14.11 The α‐globin gene cluster deletions that underlie α

thalassaem...

Figure 14.12 The molecular mechanisms that underlie the deletion forms of α‐...

Chapter 15

Figure 15.1 Induction of red cell sickling. As red cells traverse the microc...

Figure 15.2 Mechanisms of erythrocyte haemolysis, vaso‐occlusion, cell adhes...

Figure 15.3 Overwhelming pneumococcal sepsis in a 7‐year‐old child. (a) Nume...

Figure 15.4 Complications of sickle cell disease: (a) Stroke; (b) Moyamoya t...

Figure 15.5 (a) Peripheral smear from an individual with sickle cell anaemia...

Figure 15.6 Comprehensive care of patients with sickle cell disease.

Figure 15.7 Outcomes after HSCT for SCD (a) Unadjusted chronic graft versus ...

Chapter 16

Figure 16.1 Arrangement of membrane lipids. The acyl chains of the diacylpho...

Figure 16.2 Main lipids of the red cell membrane. The outer, plasma, layer c...

Figure 16.3 A schematic model of the structural organisation of the red cell...

Figure 16.4 Hereditary spherocytosis, peripheral blood. Small spherocytic re...

Figure 16.5 Osmotic fragility test in hereditary spherocytosis. Osmotic frag...

Figure 16.6 Hereditary elliptocytosis, peripheral blood. Characteristic elli...

Figure 16.7 Hereditary pyropoikilocytosis, peripheral blood. Marked anisocyt...

Figure 16.8 Hereditary stomatocytosis, peripheral blood.

Figure 16.9 Southeast Asian ovalocytosis, peripheral blood films. Mild ovalo...

Figure 16.10 McLeod syndrome, peripheral blood. Note the marked acanthocytos...

Figure 16.11 Principal pathways of energy production in the mature red cell....

Figure 16.12 The glycolytic pathway and interactions with the other metaboli...

Figure 16.13 PK deficiency, peripheral blood. (a) Red cell anisocytosis and ...

Figure 16.14 The pentose phosphate pathway. Substrates: G6P, glucose‐6‐phosp...

Figure 16.15 The glutathione (GSH) cycle and synthetic pathways. Redox contr...

Figure 16.16 G6PD deficiency. Peripheral blood film following acute oxidant ...

Figure 16.17 Pyrimidine nucleotide catabolism in the reticulocyte. Pyrimidin...

Figure 16.18 Peripheral blood film in pyrimidine 5′ ‐nucleotidase deficiency...

Chapter 17

Figure 17.1 Warm autoimmune haemolytic anaemia. Blood film showing spherocyt...

Figure 17.2 Cold haemagglutinin disease. Blood film showing gross haemagglut...

Figure 17.3

Falciparum

malaria infection (Giemsa × 100)

Figure 17.4 Microangiopathic haemolytic anaemia. Blood film from a patient w...

Figure 17.5 Oxidative haemolysis caused by drug (phenacetin). Note red cells...

Chapter 18

Figure 18.1 Diagrammatic representation of some integral red cell membrane p...

Figure 18.2 Direct and indirect antiglobulin tests. Antiglobulin antibodies ...

Figure 18.3 Enzyme‐linked immunosorbent assay (ELISA) for cell‐bound antibod...

Figure 18.4 Results of a gel microcolumn test. The subject is group B D‐nega...

Figure 18.5 Biosynthetic pathway of H antigen from its precursor, and of A a...

Figure 18.6 Diagrammatic representation of H and Lewis antigens in plasma an...

Figure 18.7 Rh and related genes (in pink) and the polypeptides they encode ...

Chapter 19

Figure 19.1 Diagrammatic representation of the preparation of components fro...

Figure 19.2 The 3 stages, a‐c, involved in the manufacture of leucodepleted ...

Figure 19.3 Mechanisms of extravascular destruction of red cells coated with...

Figure 19.4 Deaths related to TACO reported to SHOT (with imputability) 2016...

Figure 19.5 Blood film of a foetus affected by HDFN showing polychromasia an...

Figure 19.6 Blood group and antibody testing in pregnancy. If D‐negative mot...

Figure 19.7 Management algorithm for pregnancies complicated with anti‐D, an...

Figure 19.8 Middle cerebral artery Doppler. Peak velocity of systolic blood ...

Figure 19.9 Foetal haemoglobin (Hb) concentration of 48 hydropic (open circl...

Chapter 20

Figure 20.1 Lymph node with chronic lymphocytic leukaemia. (a) At low power ...

Figure 20.2 Splenic marginal zone lymphoma. (a) The spleen shows multiple no...

Figure 20.3 Plasmacytoma of the nasal cavity. (a) Atypical plasma cells embe...

Figure 20.4 Gastric marginal zone lymphoma of the mucosa‐associated lymphoid...

Figure 20.5 Nodal marginal zone lymphoma. (a) Tumour cells with a clear appe...

Figure 20.6 Follicular lymphoma. (a) The tumour grows in a follicular patter...

Figure 20.7 Follicular lymphoma of the duodenum.

Figure 20.8 Mantle‐cell lymphoma with classical (a) and pleomorphic (b) morp...

Figure 20.9 Mantle‐cell lymphoma is positive for cyclin D1.

Figure 20.10 Diffuse large B‐cell lymphoma (a) positive for CD10 (b) suggest...

Figure 20.11 Diffuse large B‐cell lymphoma with immunoblastic morphology (a)...

Figure 20.12 Intravascular lymphoma in the brain.

Figure 20.13 Primary effusion lymphoma. The tumour cells are present in the ...

Figure 20.14 Burkitt lymphoma. (a) ‘Starry sky’ pattern due to the abundant ...

Figure 20.15 Cytospin from the peripheral blood of a patient with aggressive...

Figure 20.16 Bone‐marrow involvement by EBV‐positive lymphoproliferative dis...

Figure 20.17 Lymph node infiltration in a patient with adult T‐cell leukaemi...

Figure 20.18 Destructive lesion of the nasal cavities in the course of extra...

Figure 20.19 Enteropathy‐associated T‐cell lymphoma. Remnants of the mucosa ...

Figure 20.20 Splenic red pulp involvement by hepatosplenic T‐cell lymphoma....

Figure 20.21 Example of subcutaneous panniculitis‐like T‐cell lymphoma. Feat...

Figure 20.22 Mycosis fungoides. The epidermis is infiltrated by neoplastic T...

Figure 20.23 Peripheral T‐cell lymphoma not otherwise specified. (a) The tum...

Figure 20.24 Angioimmunoblastic T‐cell lymphoma. (a) Low‐power view: note th...

Figure 20.25 Anaplastic large‐cell lymphoma, ALK

. (a) Some hallmark cells c...

Figure 20.26 Anaplastic large‐cell lymphoma, ALK

−

. (a) The tumour cons...

Figure 20.27 Nodular lymphocyte predominant (LP) B‐cell lymphoma. (a) Typica...

Figure 20.28 Classical Hodgkin lymphoma. (a) Mixed cellularity type; (b) Nod...

Chapter 21

Figure 21.1

Genetic and outcome heterogeneity within adult ALL

. (a) Distribu...

Figure 21.2 A generalised schema for treatment of adult acute lymphoblastic ...

Chapter 22

Figure 22.1 Pathogenesis of ALL.

Figure 22.2 Relationship between minimal residual disease (MRD) and relapse ...

Figure 22.3 ALLTogether1 trial risk stratification algorithm. BCP, B‐cell pr...

Figure 22.4 Development of the UKALL prognostic index using discovery (UKALL...

Chapter 23

Figure 23.1 Genetic and epigenetic events leading to CLL. The genetic and ep...

Figure 23.2 Blood film of a typical case of CLL. Small lymphocytes with scan...

Figure 23.3 Blood film from a case of transforming CLL. Note the dual popula...

Figure 23.4 Blood film from a case of polyclonal B‐cell lymphocytosis showin...

Figure 23.5 Large, blast‐like atypical cells corresponding to a case of Rich...

Figure 23.6 Treatment for patients with CLL.

Figure 23.7 Lymphocytes from a case of SMZL. Villous lymphocytes are observe...

Figure 23.8 Individual hairy cells from blood films from two patients with H...

Figure 23.9 Bone marrow trephine section of a case of HCL showing the typica...

Figure 23.10 Bone marrow trephine from a case of HCL: section embedded in me...

Figure 23.11 Blood film from a patient with mantle‐cell lymphoma cells in pe...

Figure 23.12 Blood film of a patient with follicular lymphoma presenting wit...

Figure 23.13 Blood film from a case of HCL variant showing large nucleolated...

Chapter 24

Figure 24.1 Peripheral blood smear showing T‐prolymphocytes. (a) Nuclei are ...

Figure 24.2 Peripheral T‐cell lymphoma, not otherwise specified (haematoxyli...

Figure 24.3 Angioimmunoblastic T‐cell lymphoma (Giemsa stain, magnification ...

Figure 24.4 Anaplastic large‐cell lymphoma (ALCL). (a) ALK‐positive ALCL (im...

Figure 24.5 Patches of mycosis fungoides.

Figure 24.6 Folliculotropic mycosis fungoides.

Figure 24.7 Mycosis fungoides, erythrodermic phase.

Figure 24.8 Mycosis fungoides, tumour phase.

Figure 24.9 Histological appearance of plaques of mycosis fungoides (haemato...

Figure 24.10 Histological appearance of tumours of mycosis fungoides (haemat...

Chapter 25

Figure 25.1 Classical Hodgkin lymphoma with numerous multinucleate Hodgkin R...

Figure 25.2 CD30 immunohistochemistry of classical Hodgkin lymphoma showing ...

Figure 25.3 Low‐power view of lymph node from patient with nodular sclerosis...

Figure 25.4 Nodular sclerosis classical Hodgkin lymphoma with prominent eosi...

Figure 25.5 Nodular lymphocyte predominant Hodgkin lymphoma stained for CD20...

Figure 25.6 PET scan images of patient with stage III Hodgkin lymphoma showi...

Figure 25.7 Ann Arbor lymph node groups.

Chapter 27

Figure 27.1 Evolution of the molecular classification DLBCL and related lymp...

Figure 27.2 High‐grade B‐cell lymphoma with 11q aberration (previously known...

Chapter 28

Figure 28.1

IGH

translocations in multiple myeloma.

Figure 28.2 Interactions between plasma cells and the microenvironment. See ...

Figure 28.3 Signalling pathways involved in myeloma pathogenesis. See text f...

Figure 28.4 (a) Clinical manifestations in myeloma and (b) bone marrow infil...

Figure 28.5 MRI and PET/CT in a myeloma patient. The arrows show a myeloma l...

Figure 28.6 Pathogenesis of bone disease. See text for definition of abbrevi...

Chapter 29

Figure 29.1 Macroglossia in AL amyloidosis.

Figure 29.2 Suggested approach to the investigation of suspected amyloidosis...

Figure 29.3 Appearance of amyloid in a bone marrow biopsy (×40, 6‐μm section...

Figure 29.4 Radionuclide imaging in amyloidosis: (a) Radiolabelled

123

I‐SAP ...

Figure 29.5 Improving response and decreasing mortality with wider access to...

Figure 29.6 A proposed treatment algorithm for AL amyloidosis.

Chapter 30

Figure 30.1 FA. (a) Photographs of patients with FA (A1–A3) with small mouth...

Figure 30.2 (a, b) Chromosomal abnormalities seen in FA lymphocytes followin...

Figure 30.3 Schematic representation of the FA–BRCA pathway and related netw...

Figure 30.4 Photographs of patients with DC showing abnormal skin pigmentati...

Figure 30.5 Functional overlap of DC genes involved in telomere maintenance ...

Figure 30.6 Schematic diagram showing scheme of ribosomal (r) RNA processing...

Figure 30.7 (a) CDA type I. BM aspirate showing internuclear bridging in nor...

Figure 30.8 (a) CDA type II (HEMPAS). BM aspirate showing typical multinucle...

Figure 30.9 CDA type III. Giant multinucleated erythroblast from the marrow....

Chapter 31

Figure 31.1 Overlapping bone marrow failure disorders. AA, aplastic anaemia;...

Figure 31.2 Immune‐mediated aplastic anaemia. Following an insult, most like...

Figure 31.3 (a) BM trephine – severe AA; (b) Non‐severe AA.

Figure 31.4 (a) Treatment of severe aplastic anaemia. (b) treatment of refra...

Figure 31.5 Identification of PNH red cells by flow cytometry: (a) GPI ancho...

Figure 31.6 Identification of PNH granulocytes by multicolour flow cytometry...

Figure 31.7 Breakthrough from complement blockade by eculizumab due to inade...

Figure 31.8 Urine colour with increasing eculizumab dose. Patient records ea...

Chapter 32

Figure 32.1 Incidence of AML per age group and sex in UK in 2017

Figure 32.2 Molecular landscape of AML in younger adults

Figure 32.3 Functional classification of common driver mutations in AML

Figure 32.4 Examples of different patterns of genetic clonal evolution.

Pati

...

Figure 32.5 Hierarchical approach to the classification of AML from the Inte...

Figure 32.6 Examples of the influence of gene‐gene interaction for AML progn...

Figure 32.7 Utility of MRD analysis in NPM1‐mutated AML patients. Panels (a)...

Chapter 33

Figure 33.1 (a) Blood film from a newly diagnosed CML‐CP patient aged 47 yea...

Figure 33.2 (a) The t(9;22) translocation leads to juxtaposition of genetic ...

Figure 33.3 (a and b) Formation of the

BCR::ABL1

fusion gene. Breakpoint in ...

Figure 33.4 The native ABL1 protein possesses either an auto‐inhibitory cap ...

Figure 33.5 Idealised optimal reduction in

BCR::ABL1

over duration of TKI tr...

Figure 33.6 Clinical risk scores in chronic phase CML predict cumulative inc...

Figure 33.7 Event‐free survival (EFS) from the IRIS cohort. The majority of ...

Figure 33.8 Mechanisms are implicated in treatment resistance. These factors...

Figure 33.9 Results from the randomised ENESTnd study comparing the second g...

Figure 33.10 Patients failing to achieve an early molecular response experie...

Figure 33.11 For patients with deep molecular responses, a trial of TKI cess...

Figure 33.12 Chemical structures of

BCR::ABL

inhibitors currently in clinica...

Figure 33.13 A number of critical pathways contribute to CP CML leukaemic st...

Chapter 34

Figure 34.1 Schematic overview of pathways contributing to the pathogenesis ...

Figure 34.2 Major driver genes and their pathways in MDS and MDS/MPN. The nu...

Figure 34.3 Myeloid neoplasms depicting the overlap between disease entities...

Figure 34.4 Morphology, (a) erythroid dysplasia with vacuolised erythroblast...

Figure 34.5 Bone marrow biopsies (a) haematoxylin‐eosin stained bone marrow ...

Chapter 35

Figure 35.1 Illustration of common driver mutations in ET, PV and PMF.

Figure 35.2 Typical appearance in a patient with PV.

Figure 35.3 (a) Acute cerebral infarction. A 57‐year‐old male presented 5 da...

Figure 35.4 Schematic representation of the oxygen sensing pathway. EPO, Ery...

Figure 35.5 Bone marrow trephine section (haematoxylin and eosin, H&E) from ...

Figure 35.6 Massive splenomegaly in a 53‐year‐old man with an 8‐year history...

Figure 35.7 Peripheral blood film in PMF, showing a blast, an abnormal myelo...

Figure 35.8 An example of a symptom tracker for MPN patients.

Figure 35.9 Bone marrow trephine section in PMF (H&E). Note the presence of ...

Figure 35.10 Bone marrow trephine sections from a patient with early‐stage P...

Figure 35.11 Diagnostic algorithm for systemic mastocytosis. ASM, aggressive...

Figure 35.12 Systemic mastocytosis involving the bone marrow (H&E). Malignan...

Figure 35.13 Toluidine blue stain of bone marrow aspirate (a) and trephine b...

Figure 35.14 Female with diffuse maculopapular cutaneous mastocytosis: patie...

Figure 35.15 Cardiac magnetic resonance imaging scan in a 65‐year‐old man wi...

Figure 35.16 Suggested algorithm for suspected clonal eosinophilia

Figure 35.17 Abundance of mature neutrophils and band forms in a blood film ...

Chapter 36

Figure 36.1 (a) Schematic depicting three waves of macrophage development de...

Figure 36.2 (a) Schematic comparing signal transduction activation in myelop...

Figure 36.3 Histology, touch prep images and electron microscopy.

Figure 36.4 Clockwise from top right: (a) Contrast MRI pituitary stalk enhan...

Figure 36.5 Clockwise from top right: (a) Pachymeningitis (dural thickening)...

Figure 36.6 (a) The main features of JXG showing from left to right: superfi...

Figure 36.7 A schematic showing the main cellular circuit and risk factors p...

Chapter 37

Figure 37.1 Diagrammatic representation of HLA class I and II molecules show...

Figure 37.2 Pathophysiology of acute GVHD (a) and chronic GVHD (b). See text...

Figure 37.3 ‘Pre‐emptive’ mobilisation schedule.

Figure 37.4 Causes of death after stem cell transplantation in (a) autologou...

Figure 37.5 Acute skin GVHD: (a) acute cutaneous GVHD; (b) chronic oral GVHD...

Figure 37.6 Temporal pattern of infectious complications after allogeneic st...

Figure 37.7 Clinical manifestations of chronic GVHD.

Chapter 38

Figure 38.1 Detection of clonality through X‐chromosome inactivation pattern...

Figure 38.2 Relative prevalence of mutations in different CH driver genes. T...

Figure 38.3 CH prevalence and detection in the general population. (a) Diffe...

Figure 38.4 Clonal selection and its influence on HSC composition over life....

Figure 38.5 Median number of coding mutations in normal‐aged HSCs and in dif...

Figure 38.6 Changing spectra of CH‐driving mutations with advancing age.

DNM

...

Figure 38.7 Driver gene spectra in different contexts. HSCs acquire somatic ...

Figure 38.8 Lifelong driver‐specific patterns of clonal growth.

DNMT3A

‐mutan...

Chapter 39

Figure 39.1 The haemostasis network. The network includes elements of coagul...

Figure 39.2 The coagulation cascade. The traditional concept of blood coagul...

Figure 39.3 The haemostasis network: fibrin generation. Following vascular d...

Figure 39.4 The haemostasis network: inhibition of thrombin generation. The ...

Figure 39.5 The haemostasis network: fibrinolysis. Both PLG and tPA bind to ...

Figure 39.6 Blood vessel architecture and functions in haemostasis. (a) The ...

Figure 39.7 Role of von Willebrand factor (VWF) in haemostasis. (a) VWF doma...

Figure 39.8 Modular organisation of haemostasis proteins. The evolutionary r...

Chapter 40

Figure 40.1 Functional roles of the platelet in the vasculature.

Figure 40.2 Thrombus formation at arteriolar rates of shear. Platelets are (...

Figure 40.3 Platelet adhesion and aggregation at arteriolar shear. Human blo...

Figure 40.4 Morphological changes in washed human platelets followed adhesio...

Figure 40.5 Schematic of major tyrosine kinase‐linked and G protein‐coupled ...

Figure 40.6 Schematic of ITAM signalling. An ITAM has the conserved sequence...

Chapter 41

Figure 41.1 Radiograph of knee joint showing advanced haemophilic arthropath...

Figure 41.2 Orthopaedic joint scores for patients intensively treated in the...

Figure 41.3 The

FVIII

gene and protein. Top line, scale for gene in kilobase...

Figure 41.4 How the tip flips: the mechanism of inversion through intron 22....

Figure 41.5 The domain structure of the primary VWF translation product. The...

Figure 41.6 Assembly of FVIII–VWF complex. FVIII synthesised by endothelial ...

Figure 41.7 Multimer analysis of VWF from patients with VWD and normal contr...

Chapter 42

Figure 42.1 Worldwide distribution of rare coagulation disorders derived fro...

Chapter 43

Figure 43.1 The changes in disseminated intravascular coagulation are compar...

Figure 43.2 Changes in routine coagulation tests associated with COVID‐19 in...

Figure 43.3 Vitamin K metabolism.

Figure 43.4 Haemostatic disturbance in liver disease. The haemostatic system...

Figure 43.5 Mechanisms of haemostatic dysfunction during severe trauma.

Figure 43.6 Diagnostic algorithm for an isolated prolonged APTT and possible...

Chapter 44

Figure 44.1 Schematic representation of the complex structure of platelets. ...

Figure 44.2 Flowchart for the investigation of a suspected platelet disorder...

Chapter 45

Figure 45.1 Model of cell‐mediated cytotoxicity in chronic ITP. In the case ...

Figure 45.2 Thrombopoietin levels are usually normal or only slightly raised...

Figure 45.3 Pathogenesis of ITP. (a) Platelets are produced by megakaryocyte...

Chapter 46

Figure 46.1 Domain structure of ADAMTS13. TSP1: thrombospondin 1; RGDS: Arg‐...

Figure 46.2 Pathophysiology of TTP. VWF is secreted from endothelial cells i...

Figure 46.3 Pathophysiology of STEC HUS. Verocytotoxin, Shiga toxin or Shiga...

Figure 46.4 Pathophysiology of aHUS. An excessive activation of C3 convertas...

Figure 46.5 Differential diagnosis of patients with a suspected aHUS, TTP or...

Chapter 47

Figure 47.1 Sites of action of antiplatelet drugs. Aspirin inhibits the synt...

Figure 47.2 Catalysis of antithrombin‐mediated inhibition of thrombin or fac...

Figure 47.3 Mechanism of action of warfarin. A racemic mixture of

‐ and

‐e...

Chapter 48

Figure 48.1 (a) The model assumes that there is a thrombosis threshold that,...

Figure 48.2 Cumulative recurrence of venous thrombosis in consecutive patien...

Chapter 49

Figure 49.1 (a) Diagnostic algorithm for DVT with scanning of proximal veins...

Figure 49.2 Diagnostic algorithm for PE.

Chapter 50

Figure 50.1 upper panel: physiological defence mechanisms of the vascular en...

Figure 50.2 Left panel shows sites of interaction and mechanistic pathways i...

Figure 50.3 Timely use of antithrombotic therapy in the acute phase of ACS...

Figure 50.4 Optimal duration of dual antiplatelet therapy (DAPT) DAPT decrea...

Figure 50.5 captures the main mechanisms involved in thrombogenesis during a...

Chapter 51

Figure 51.1 Cases of malaria in the United Kingdom: 1999–2018

Figure 51.2 Life cycle of the malaria parasite.

Figure 51.3 Stages in the life cycle of

Plasmodium falciparum

in Giemsa‐stai...

Figure 51.4 Global distribution of lymphatic filariasis.

Figure 51.5 Microfilariae of

W. bancrofti

in thick film: (a) microfiliaria s...

Figure 51.6 Global distribution of African trypanosomiasis.

Figure 51.7 Global distribution of visceral leishmaniasis.

Figure 51.8 Bone marrow aspirate of leishmaniasis infection showing a macrop...

Figure 51.9 Patient with massive splenomegaly due to hyper‐reactive malarial...

Chapter 52

Figure 52.1 Biochemistry of lysosomal storage disorders.

Figure 52.2 Gaucher cells in the bone marrow.

Figure 52.3 MRI scan showing skeletal changes in Gaucher disease.

Figure 52.4 Renal biopsy in Fabry disease showing accumulation of inclusions...

Chapter 53

Figure 53.1 Causes of thrombocytopenia in pregnancy.

Occur only during ...

Figure 53.2 Example protocol for the management of obstetric haemorrhage

Figure 53.3 Management of MPN in pregnancy. *High‐risk pregnancy criteria ma...

Chapter 54

Figure 54.1 Typical erythrocyte morphology in a preterm neonate. Crenated re...

Figure 54.2 A diagnostic algorithm for neonatal anaemia. The most useful scr...

Figure 54.3 Blood film from a neonate with Diamond–Blackfan anaemia. This ba...

Figure 54.4 Pearson syndrome. Bone marrow aspirate from a neonate with Pears...

Figure 54.5 Haemolytic disease of the newborn. (a) Blood film from a baby wi...

Figure 54.6 Red cell membrane disorders. (a) Blood film from a baby with her...

Figure 54.7 Infantile pyknocytosis. Blood film from a neonate with infantile...

Figure 54.8 α‐Thalassaemia major. Blood film from a neonate with α‐thalassae...

Figure 54.9 Fetomaternal haemorrhage. (a) Blood film from a neonate with a h...

Figure 54.10 Transient leukaemia in a neonate with Down syndrome. Leucoeryth...

Chapter 57

Figure 57.1 TEG and ROTEM traces. Thromboelastography (TEG) and thromboelast...

Figure 57.2 Major haemorrhage protocol

Guide

Cover Page

Title Page

About the editors

Contributor’s list

Preface to the eighth edition by Adam J Mead

Preface to the first edition

About the companion website

Table of Contents

Begin Reading

Index

WILEY END USER LICENSE AGREEMENT

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