Postgraduate Haematology (eBook)

Douglas R. Higgs, A. Victor Hoffbrand, David M. Keeling, Atul B. Mehta (Herausgeber)

eBook Download: PDF

2015 | 7. Auflage
952 Seiten
Wiley (Verlag)
978-1-118-85447-1 (ISBN)

Infos

This comprehensive textbook is the key resource for postgraduate trainees or residents in haematology. Now in its seventh edition, the book continues to provide everything the reader needs for examination preparation or clinical practice.

Postgraduate Haematology discusses up-to-date knowledge of the pathogenesis, clinical and laboratory features, management and treatment of a wide range of blood and bone marrow disorders in a concise and user friendly style. It presents essential information for everyday use and teaching, as well more detailed scientific background for more in-depth reading, accompanied by thoughtful referencing. 

The clearly illustrated full-colour figures and charts demonstrate key facts, and are supplemented by numerous high quality photomicrographs of blood cells and tissues. Over 51 chapters from international authors, including the WHO Classification of Haematopoietic and Lymphoid Tissues, Postgraduate Haematology provides an expert review of malignant and non-malignant haematology.

• New sections reflect advances in the specialty, e.g. knowledge gained from new generation sequencing, latest anticoagulant drugs, diagnostic laboratory tools, and treatment strategies
• Superb four-color illustrations and photomicrographs of blood cells and tissues throughout
• Includes algorithms to aid with decision-making for treatment
• Companion website featuring figures and tables from the book

Arm yourself with the textbook of choice for trainees and practitioners in haematology.

A. Victor Hoffbrand, MA, DM, FRCP, FRCPath, FRCP (Edin), DSc, FMedSci, Emeritus Professor of Haematology at University College London, London, UK.

Douglas R. Higgs, MD, FRCP, FRS, Professor of Molecular Haematology & Director, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.

David Keeling, Consultant in Haemophilia and Thrombosis, Oxford Haemophilia and Thrombosis Centre, Oxford University Hospitals, Oxford, UK.

Atul B. Mehta MA, MD, FRCP, FRC Path, Consultant Haematologist & Clinical Director, RFH Lysosomal Storage Disorders Unit, Royal Free Hospital, London, UK.

Inhalt

Postgraduate Haematology 3
Contents 7
Contributor list 9
Preface to the seventh edition 12
Preface to the first edition 13
1 Stem cells and haemopoiesis 15
Introduction 15
Hierarchical organization and lineage relationships in the adult haemopoietic system 15
Sites of adult haemopoiesis 17
Development of HSCs 17
Waves of haemopoietic generation in embryonic development 17
Embryonic haemopoietic sites and haemopoietic migration 19
HSC quiescence, proliferation and ageing 20
Haemopoietic-supportive microenvironments 20
Adult bone marrow microenvironment 20
Microenvironments important for haemopoietic development in the conceptus 21
Haemopoietic regenerative and replacement therapies 22
Stem cell transplantation 22
Gene therapy and gene editing for haemopoietic disease 22
New sources of HSCs for transplantation 23
Embryonic stem cells and induced pluripotent stem cells 23
Selected bibliography 24
2 Erythropoiesis 25
Introduction 25
The origins of erythroid cells during development 25
Specifying the erythroid lineage 26
Expression of critical transcription factors specifies the erythroid lineage 26
Terminal maturation of committed erythroid cells 27
Changes in the expression of transcription factors during terminal maturation 27
Changes in the expression of erythroid proteins during terminal maturation 28
Control of erythropoiesis via cell signalling 29
The erythroid niche 31
Red cell senescence and clearance 32
Assessing erythropoiesis 33
Conclusions 34
Selected bibliography 34
3 Iron metabolism, iron deficiency and disorders of haem synthesis 35
Introduction 35
Distribution of body iron 35
Proteins important in iron metabolism 35
Haem proteins and iron-containing enzymes 35
Ferritin and haemosiderin 36
Transferrin and transferrin receptors 36
Divalent metal transporter 1 39
Ferroportin 39
Other proteins 39
Hepcidin 40
Matriptase-2 40
Intracellular iron homeostasis 41
Normal iron balance 41
Iron absorption 41
Dietary and luminal factors 42
Mucosal factors: molecular aspects of iron absorption and its regulation 42
Iron uptake by erythroid cells 42
Haem synthesis and mitochondrial iron metabolism 43
Intracellular transit iron and plasma non-transferrin-bound iron 44
Breakdown of haemoglobin 44
Diagnostic methods for investigating iron metabolism 44
Storage iron 45
Iron supply to the tissues 45
Iron deficiency anaemia 46
Sequence of events 46
Causes of iron deficiency (Table 3.4) 47
Management of iron deficiency 48
Iron refractory iron deficiency anaemia 49
Pathological alterations in haem synthesis 49
Porphyrias 49
Lead poisoning 50
Sideroblastic anaemia 50
Selected bibliography 53
4 Iron overload 54
Introduction 54
Hereditary haemochromatosis 54
HFE haemochromatosis 54
Non-HFE haemochromatosis 58
Other causes of iron overload 59
Iron-loading anaemias 59
Tests of body iron burden 60
Iron chelation therapy 62
Non-transfusion-dependent thalassaemia (NTDT) 65
Acute iron poisoning 65
Selected bibliography 65
5 Megaloblastic anaemia 67
Introduction 67
Underlying basic science 67
Biochemical basis of megaloblastic anaemia 67
Cobalamin–folate relationship 67
Clinical features 68
General tissue effects of cobalamin and folate deficiencies 68
Neurological manifestations 71
Haematological findings 71
Peripheral blood 71
Bone marrow 72
Chromosomes 73
Ineffective haemopoiesis 73
Cobalamin 73
Dietary sources and requirements 73
Absorption 73
Enterohepatic circulation 74
Transport 74
Cobalamin analogues 75
Causes of cobalamin deficiency 75
Diagnosis of cobalamin deficiency 78
Tests for the cause of cobalamin deficiency 79
Folate 79
Dietary folate 79
Body stores and requirements 80
Absorption 80
Enterohepatic circulation 80
Transport 80
Biochemical functions 80
Causes of folate deficiency (Table 5.6) 81
Diagnosis of folate deficiency 83
General management of megaloblastic anaemia 83
Treatment of cobalamin deficiency 83
Treatment of folate deficiency 84
Folinic acid (5-formyl-THF) 84
Prophylactic folic acid 84
Pregnancy 84
Prematurity 84
Megaloblastic anaemia not due to cobalamin or folate deficiency or altered metabolism 84
Other nutritional anaemias 85
Protein deficiency 85
Scurvy 85
Other deficiencies 85
Selected bibliography 85
6 Haemoglobin and the inherited disorders of globin synthesis 86
Introduction 86
The structure, genetic control and synthesis of haemoglobin 86
Genetic control, regulation and synthesis 88
Classification of the disorders of haemoglobin 91
The thalassaemias and related disorders 91
Definition and classification 91
The ??????-thalassaemias 92
????????????--Thalassaemia and hereditary persistence of fetal haemoglobin 101
????????????????????????-Thalassaemia 103
The ??????-Thalassaemias 103
Thalassaemia intermedia, non-transfusion-dependent thalassaemia 107
Screening for thalassaemias 108
Structural haemoglobin variants related to thalassaemia (Table 6.3) 109
The unstable haemoglobin disorders 109
High-oxygen-affinity haemoglobin variants 110
Low-oxygen-affinity haemoglobin variants 110
Congenital methaemoglobinaemia due to haemoglobin variants 111
Acknowledgement 111
Selected bibliography 111
7 Sickle cell disease 112
Introduction 112
Geographic distribution of sickle mutation 112
Pathophysiology 112
Molecular basis of sickling 112
Effect on erythrocytes 113
Vaso-occlusion 113
Haemolysis 114
Clinical manifestations 114
Anaemia 115
Acute painful episode 116
Growth and development 116
Infections 116
Neurological complications 116
Pulmonary complications 119
Hepatobiliary complications 119
Pregnancy 119
Renal complications 120
Priapism 120
Ocular complications 120
Bone complications 120
Leg ulcers 120
Variant sickle cell syndromes 121
Sickle cell trait 121
HbSC disease 121
Sickle cellb-thalassaemia 121
Sickle cell anaemia with coexistent ??????-thalassaemia 121
Sickle cell/HPFH 121
Other sickling syndromes 121
Diagnosis 122
Peripheral blood findings 122
Other laboratory tests 122
Haemoglobin electrophoresis 122
Other tests to detect sickle haemoglobin 122
Newborn screening 122
Prenatal diagnosis 122
Therapy 123
Routine healthcare 123
Infections 124
Transfusion therapy 124
Pain management 125
Hydroxycarbamide 125
New therapeutic modalities 125
Haemopoietic stem cell transplantation 126
Psychosocial issues 126
Selected bibliography 127
8 Hereditary disorders of the red cell membrane and disorders of red cell metabolism 128
Haemolysis 128
Definitions 128
General features of haemolysis 128
Classification 129
Red cell membrane disorders 129
The red cell membrane 129
The integral proteins and vertical interaction 130
The clinical phenotypes of hereditary membrane disorders 132
Hereditary spherocytosis 132
Hereditary elliptocytosis 134
Hereditary stomatocytosis and related disorders 136
Southeast Asian ovalocytosis 137
Abnormalities of membrane lipids 138
Defects of red cell metabolism 138
The glycolytic pathway (Embden–Meyerhof pathway) 139
The Rapoport–Luebering shunt 139
Disorders of the glycolytic pathway 139
Other defects of the enzymes of the glycolytic system 142
Defence against oxidative stress: the production of reducing power 145
Pentose phosphate pathway (hexose monophosphate shunt) 145
Glucose-6-phosphate dehydrogenase deficiency 146
Glutathione 149
Nucleotide metabolism 150
Pyrimidine 5’-nucleotidase 150
Selected bibliography 150
9 Acquired haemolytic anaemias 152
Introduction 152
Immune haemolytic anaemias 152
Autoimmune haemolytic anaemia 152
Antibody characteristics and specificity of red cell autoantibodies 153
Mechanisms for immune red cell destruction 154
Other factors influencing red cell destruction and production 155
Warm-type autoimmune haemolytic anaemias 155
Cold-type autoimmune haemolytic anaemias 158
Alloimmune haemolytic anaemia 160
Non-immune acquired haemolytic anaemias 162
Infections causing haemolytic anaemia 162
Fragmentation haemolysis: mechanical haemolytic anaemias 164
Chemical and physical agents 167
Acquired disorders of the red cell membrane 168
Selected bibliography 169
10 Inherited aplastic anaemia/bone marrow failure syndromes 170
Introduction 170
Fanconi anaemia 170
Clinical features 170
Cell and molecular biology 173
Treatment 175
Dyskeratosis congenita 176
Clinical features 176
Cell biology and link to other diseases 176
Treatment 179
Shwachman–Diamond syndrome (SDS) 179
Clinical features 179
Cell and molecular biology 180
Treatment 180
Diamond–Blackfan anaemia (DBA) 181
Clinical features 181
Cell and molecular biology 181
Treatment 182
Congenital dyserythropoietic anaemia (CDA) 182
CDA type I 182
CDA type II 183
CDA type III 183
Treatment 184
Congenital and cyclical neutropenias 184
Thrombocytopenia with absent radii (TAR) 185
Congenital amegakaryocytic thrombocytopenia (CAMT) 185
Conclusion 185
Acknowledgements 187
Selected bibliography 187
11 Acquired aplastic anaemia and paroxysmal nocturnal haemoglobinuria 188
Acquired aplastic anaemia 188
Characterization and definition 188
Epidemiology 188
Pathogenesis and its clinical relevance 189
Detection of somatic mutations in AA 193
Clinical features 193
Diagnostic investigations and differential diagnosis (Table 11.1) 194
Management 194
Haemopoietic stem cell transplantation 199
Paroxysmal nocturnal haemoglobinuria 201
Introduction 201
Pathophysiology 201
Epidemiology 201
Clinical features 202
Investigation 203
Treatment 204
Pregnancy in PNH 206
Prognosis 206
Future challenges and developments 207
Suggested further reading 208
Clinical significance of acquired somatic mutations in AA 208
Selected bibliography 208
12 Red cell immunohaematology 209
Introduction 209
Blood group systems 209
The red cell membrane and chemistry of blood group antigens 209
Blood group antibodies 211
Naturally occurring and immune antibodies 211
Cold and warm antibodies 211
IgM and IgG 212
Monoclonal antibodies 212
Lectins 212
Clinical significance of red cell antibodies 212
Detection of red cell antigen–antibody reactions 213
Agglutination techniques 213
Haemolysis 214
Adsorption and elution tests 214
Specialized antiglobulin techniques 214
Microcolumn tests (gel and beads) 214
Microplate techniques 215
Automated techniques 215
Blood grouping reagents 215
Antibody screening and identification 215
Molecular techniques for blood grouping 216
The ABO system 216
Antigens of the ABO system 216
Antibodies of the ABO system 218
Biochemistry and biosynthesis of ABH antigens 218
The Lewis system 219
Lewis antigens and their biosynthesis 219
Lewis antibodies 220
P blood groups 221
I and i antigens and antibodies 221
The Rh system 221
Rh antigens 221
Probable Rh genotype 222
Molecular genetics of Rh 222
The Band 3/Rh molecular macrocomplexes 222
Variants of D 223
Antibodies of the Rh system 223
Prediction of fetal Rh genotype by molecular methods 224
The MNS system 224
Antigens of the MNS system 224
Antibodies of the MNS system 224
The Kell blood group system 224
Some other blood group systems 225
Polyagglutinable red cells 226
The biological significance of blood group antigens 226
Selected bibliography 227
13 Clinical blood transfusion 228
Introduction 228
Blood transfusion and regulatory aspects 228
The blood donor (Tables 13.1 and 13.2) 228
Selection criteria and blood donation 228
Transfusion-transmitted infection (TTI) 229
Hepatitis viruses 231
Human immunodeficiency virus (HIV-l and HIV-2) 232
Human T-cell leukaemia viruses 232
Cytomegalovirus 232
Syphilis 233
Malaria 233
Other infections 233
Bacteria 233
Laboratory tests on blood donations 234
Storage and Processing of Blood 234
Anticoagulants and optimal additive solutions 236
Leucodepletion 236
Red cells 236
Platelet preparations 236
Granulocyte concentrates 237
Fresh-frozen plasma (FFP) 238
Irradiated blood components 238
Clinical and laboratory transfusion practice 238
EU Blood Directives (UK Blood Safety & Quality Regulations 2005): impact on hospital transfusion practice
Laboratory tests in patients 239
Pretransfusion group and screen 239
Compatibility testing (cross-match) 239
Special requirements for the selection of blood 240
Haemoglobinopathy 240
Haemato-oncology 240
Antenatal testing 240
Neonatal ‘top-up’ transfusion 240
Transfusion in autoimmune haemolytic anaemia 241
Safe administration of blood 242
Patient identification 242
Detection and approach to transfusion reactions 242
Complications of blood transfusion 242
Immunological complications 242
Non-immunological complications of blood 248
Other adverse effects of transfusion 248
Haemovigilance 249
Appropriate use of blood and alternatives to allogeneic blood transfusion 249
Patient blood management (PBM) 249
Clinical decision to transfuse 251
Strategies to minimize transfusion of blood and components 251
Red cell transfusion triggers 251
Platelet transfusions 252
Use of fresh frozen plasma and cryoprecipitate 252
Major haemorrhage 252
Haemolytic disease of the fetus and newborn (HDFN) 253
Neonatal alloimmune thrombocytopenia 258
Selected bibliography 258
14 Phagocytes 260
Introduction 260
Mechanisms of phagocyte function 260
Locomotion 260
Phagocyte receptors 262
Phagocytic signalling 262
Degranulation and secretion 263
Phagocytic killing: the respiratory burst 263
Phagocytic killing: nitric oxide 264
Phagocytic killing: antimicrobial proteins 264
Production, structure and dysfunction of phagocytes 265
Neutrophils (Figure 14.2a) 265
Eosinophils (Figure 14.2b) 274
Basophils and mast cells (Figure 14.2c) 277
Monocytes and macrophages (Figure 14.2d,e) 279
Selected bibliography 283
15 Lysosomal storage disorders 284
Lysosomes 284
Pathophysiology of lysosomal storage disorders 284
Prevalence 285
Diagnosis 285
General aspects of therapy 285
Prognosis 286
Clinical manifestations 286
Gaucher disease 286
Fabry disease 289
Pompe disease 290
Niemann–Pick disease 290
Selected bibliography 290
16 Normal lymphocytes and non-neoplastic lymphocyte disorders 292
Introduction 292
The anatomy of the immune system 292
Nature of the antigen-specific receptors on T and B cells 293
Antigen recognition by lymphocytes 293
Biological and physical properties of immunoglobulins 294
Complement 297
The opsonization phase of the complement sequence (Figure 16.7) 298
The lytic phase of the complement sequence (Figure 16.7) 299
Polymorphism of MHC molecules 300
Generation of antigen-specific receptors on T and B lymphocytes 300
B lymphopoiesis 301
T-cell production and selection in the thymus 301
TCR gene rearrangements and phenotypic changes 303
The B-cell repertoire 303
The T-cell repertoire 304
CD4+ and CD8+ T cells and their functions 304
Natural killer cells 305
Natural killer T cells 306
The immune response 306
Immunoglobulin class switching 309
Differentiation of primed T cells into effector cells 309
Regulatory CD4+ T cells 309
The role of co-stimulatory blockade in the treatment of malignant disease 310
Chimeric antigen receptors in the treatment of haemopoietic malignancy 310
Cytokines and their classification 310
Chemokines and their classification 311
Interpretation of blood lymphocyte counts 311
Infectious mononucleosis 314
Clinical features 314
Blood picture 314
Serological changes 314
Differential diagnosis and treatment 315
Secondary associations of infectious mononucleosis 315
Selected bibliography 316
17 The spleen 317
Evolution of the spleen 317
Structure and function 317
Splenic blood flow and the red pulp 318
Blood pooling 319
Role of the spleen in ensuring quality control of red cells 319
Immunological function 319
Extramedullary haemopoiesis 320
Splenomegaly and hypersplenism 320
Spleen size 320
Causes of splenomegaly 320
Hypersplenism 322
Splenectomy 322
Complications of splenectomy 323
Hyposplenism 326
Red cell changes 326
Leucocyte changes 327
Platelet changes 327
Immunological effects 327
Selected bibliography 327
18 The molecular basis of haematological malignancies 328
Introduction 328
The cancer genome 328
Classes of DNA mutations 331
Inherited predisposition to haematological cancers 332
Acquired DNA mutations in haematological cancers 333
From genotype to phenotype 335
NOTCH-signalling and lymphoid malignancies 335
Epigenetics and leukaemia 336
Multiple myeloma 341
Clonal evolution and subclonal architecture of haematological cancers 342
Clonal evolution of cancer 342
Impact of clonal structure on treatment and relapse 343
Selected bibliography 344
19 Laboratory diagnosis of haematological neoplasms 346
Introduction 346
Blood count and blood film 346
Bone marrow aspirate 348
Bone marrow trephine biopsy 350
Cytochemistry 352
Histology 352
Flow cytometric immunophenotyping 353
Immunohistochemistry 355
Cytogenetic analysis 356
Fluorescence in situ hybridization 357
Molecular genetic analysis 358
Whole-genome scanning 362
Microarray analysis of gene expression 363
Next-generation sequencing (NGS) 364
Laboratory techniques and the WHO classification of tumours of haemopoietic and lymphoid tissues 364
Conclusions 364
Selected bibliography 364
20 Acute myeloid leukaemia 366
Disease epidemiology 366
Pathophysiology and clinical features 366
Disease classification 367
Cytogenetics and molecular genetics 367
Treatment 368
Aspirations for treatment 368
Treatment strategy 369
Treatment details 371
Consolidation treatment 373
Factors influencing the risk of relapse 376
Cytogenetics 376
Age 377
Response to induction chemotherapy 377
FLT3-ITD mutation 377
Other molecular abnormalities 378
Performance score 379
White cell count 379
Resistance proteins 379
Detection of measurable/minimal residual disease (MRD) 380
Impact of prognostic factors on treatment choice 381
Acute promyelocytic leukaemia 381
Treatment in the older patient 382
Management of relapse 382
Future developments 383
Classification 383
Therapeutics 383
Selected bibliography 384
21 Adult acute lymphoblastic leukaemia 385
Introduction 385
Diagnosis of adult ALL 385
Morphology 385
Cell-surface marker analysis 386
B-lineage ALL 386
T-lineage ALL 386
Cytogenetics 387
Minimal residual disease (MRD) 387
Prognostic and predictive factors in ALL 388
Initial approach to a patient with ALL 389
Clinical presentation 389
Diagnostic approach 389
Supportive care (see also Chapter 23) 389
Specific treatment of ALL 391
Prephase 391
Induction therapy 391
Toxicity during induction 393
Consolidation therapy 394
Maintenance therapy 394
CNS-directed therapy 394
Treatment of CNS disease at diagnosis 395
Stem cell transplantation 395
Specific approaches to defined clinical populations in the treatment of ALL 395
Targeted therapies for ALL: Philadelphia chromosome positive (Ph+) disease 395
Teenagers and young adults (TYA) 395
ALL in older adults 396
Treatment of relapsed/refractory disease 396
Selected bibliography 397
22 Childhood acute lymphoblastic leukaemia 398
Introduction 398
Epidemiology 398
Aetiology 398
Genetic factors 398
Environmental factors 399
Pathogenesis (Figure 22.1) 399
Clinical features 400
Differential diagnosis 400
Laboratory features 401
Immunophenotypic classification (see also Chapter 19) 402
Early pre-B-ALL 402
Pre-B-ALL 402
(Mature) B-cell ALL 402
T-lineage ALL 402
Cytogenetic and molecular classification 402
Hyperdiploid and hypodiploid ALL 402
ALL with TEL–AML1 (ETV6–RUNX1) rearrangements 403
ALL with E2A–PBX1 (TCF3–PBX1) rearrangements 403
ALL with MLL gene rearrangements 403
ALL with BCR–ABL1 rearrangements 403
ALL with iAMP21 403
Genetic abnormalities in T-cell ALL 404
Novel genetic subtypes of ALL 404
Prognostic factors 404
Presenting features 404
Early response 405
Minimal residual disease 405
Pharmacogenetic variables 406
Treatment 406
Drugs and protocols 406
Historical background 406
Current UK strategy 406
Current outcomes 409
Treatment of distinct sub-groups 410
Relapse 411
Early and late toxicity (Table 22.4) 411
Treatment in a resource-poor setting 411
Future strategies and conclusions 412
Acknowledgements 412
Selected bibliography 412
23 Supportive care in the management of leukaemia 413
Introduction 413
Psychological 413
Social 414
Financial 414
Reproductive 414
Fertility preservation 414
GnRH-a 414
Anaemia 414
Use of erythroid-stimulating agents (ESA) 415
Special considerations 415
Thrombocytopenia 415
Platelet preparations 416
TPO receptor agonists 416
Granulocyte transfusions 416
Granulocyte colony-stimulating factor (G-CSF) 416
Infections 417
Febrile neutropenia 417
Empirical antibiotic therapy 417
Investigating febrile neutropenic episodes 419
Respiratory system 423
Gastrointestinal system 424
Skin 424
Vascular access devices 424
Antibiotic resistance 424
Investigation of persistent fever 425
When to stop anti-infective agents 425
Special considerations in bone marrow Allo SCT recipients 427
Conclusions 428
Chemotherapy-induced nausea and vomiting (CINV) 428
Non-pharmacological strategies 428
Nutritional 428
Metabolic complications 428
Fluid balance 428
Hydration prior to cytotoxic agents 429
Tumour lysis syndrome 429
Hyperleucocytosis 429
Differentiation syndrome (DS) 430
Skin, nail and dental problems 430
Radiation recall 430
Dental problems 431
Auditory toxicity 431
Visual toxicity 431
Pain 431
Palliation 431
Selected bibliography 432
24 Chronic myeloid leukaemia 433
Introduction 433
Epidemiology and aetiology 433
Clinical features, natural history, laboratory haematology and cytogenetics 433
Chronic phase (CP) 434
Accelerated phase (AP) 434
Blastic phase (BP) 434
Cytogenetics and molecular biology 435
Measurement of residual disease and monitoring with cytogenetics and BCR–ABL1 RQ-PCR 439
Treatment 440
Imatinib 440
Nilotinib 441
Dasatinib 442
Bosutinib 443
Ponatinib 444
Choice of TKI up front 444
Treatment goals 444
Duration of treatment 445
Treatment resistance 445
Advanced phase diseases 447
Fertility preservation and pregnancy 448
Haemopoietic stem cell transplantation 449
Atypical CML/chronic neutrophilic leukaemia (see also Chapters 25 and 26) 450
Prospects 450
Acknowledgement 451
Selected bibliography 451
25 The myelodysplastic syndromes 452
Introduction 452
History 452
Incidence 452
Aetiology 453
Classification 453
FAB classification 453
WHO classification 453
Pathogenesis 455
MDS: a clonal expansion of HSCs with ineffective haemopoiesis and leukaemic transformation 455
Immunological abnormalities in MDS 456
Apoptosis in MDS 457
Cytogenetic abnormalities in MDS 457
SNP-A karyotyping 458
Deletion chromosome 5q 458
Chromosome 7 abnormalities 460
Molecular basis of MDS 460
Genetic abnormalities in MDS: candidate genes and whole-genome sequencing 461
Diagnosis 468
Clinical features 468
Blood count 468
Peripheral blood morphology 468
Bone marrow morphology (see also Chapter 19) 468
Bone marrow histology 471
Cytogenetic abnormalities in MDS 471
Molecular abnormalities in MDS 471
Other investigations 472
Natural history and prognostic factors 472
Natural history 472
International Prognostic Scoring System 472
WHO Classification-based Prognostic Scoring System 473
Revised International Prognostic Scoring System 474
Molecular mutations and prognostic scoring systems 475
Management and treatment 475
Supportive care 476
Haemopoietic growth factors 476
Immunosuppression 477
Chelation therapy 477
Intensive chemotherapy 478
Allogeneic stem cell transplantation 478
Hypomethylating drugs 480
Lenalidomide 480
Therapeutic strategy 482
Myelodysplastic/myeloproliferative diseases 483
Chronic myelomonocytic leukaemia 483
Juvenile myelomonocytic leukaemia 486
Refractory anaemia with ring sideroblasts and thrombocytosis 486
Myelodysplasia of childhood 486
Future directions 487
Selected bibliography 487
26 Myeloproliferative neoplasms 488
Introduction 488
The polycythaemias 488
Polycythaemia vera 488
Other causes of erythrocytosis 493
Essential thrombocythaemia 496
Pathophysiology 496
Clinical features 496
Investigations 497
Reactive thrombocytosis 497
Other clonal thrombocytoses 497
Treatment 498
Prognosis 499
ET and pregnancy 499
Primary myelofibrosis 499
Pathophysiology 500
Clinical features 500
Investigations 501
Treatment 502
Prognosis 504
Mastocytosis 504
Pathophysiology 505
Clinical features 505
Investigations 506
Treatment 506
Future treatments 507
Prognosis 508
Clonal hypereosinophilic syndromes 508
Pathophysiology 508
Clinical features (see also Chapter 14) 509
Investigations 509
Treatment 510
Prognosis 510
Chronic neutrophilic leukaemia 510
Pathophysiology 511
Clinical features and treatment 511
Neutrophilic chronic myeloid leukaemia 511
Transient abnormal myelopoiesis of Down syndrome 512
Incidence, clinical features and treatment 512
Pathophysiology 512
Selected bibliography 512
27 Chronic lymphocytic leukaemia and other chronic B-cell disorders 514
Introduction 514
General aspects of diagnostic methodology (see also Chapter 19) 514
Chronic lymphocytic leukaemia 514
Definition 514
Epidemiology 515
Genetic predisposition 515
Pathogenesis 515
Clinical features 516
Laboratory features (see also Chapter 31) 516
Genetic and molecular features 517
Pathology features 518
Diagnostic criteria 518
Differential diagnosis 518
Diagnosis of CLL-related conditions 520
Prognosis 521
Disease complications 524
Treatment 526
Other B-cell chronic disorders 532
B-cell prolymphocytic leukaemia 532
Hairy-cell leukaemia 533
The leukaemic phase of indolent NHL 534
Follicular lymphoma 535
Splenic marginal zone lymphoma 535
Mantle cell lymphoma 536
Acknowledgements 536
Selected bibliography 536
28 T-cell lymphoproliferative disorders 538
Introduction 538
Chronic T-cell leukaemias 538
T-prolymphocytic leukaemia 538
Large granular lymphocyte leukaemia 539
Peripheral T-cell non-Hodgkin lymphomas 540
Peripheral T-cell non-Hodgkin lymphoma, not otherwise specified 541
Angioimmunoblastic T-cell lymphoma 541
Anaplastic large-cell lymphoma 542
Other disease entities 543
Treatment of peripheral T-cell non-Hodgkin lymphomas 544
Cutaneous T-cell non-Hodgkin lymphomas 545
Mycosis fungoides 545
Sézary syndrome 548
Primary cutaneous CD30+ lymphoproliferative disorders 549
Conclusions 550
Acknowledgements 550
Selected bibliography 550
29 Multiple myeloma 551
Definition 551
Epidemiology and aetiology 551
Pathogenesis 551
Cellular origin of myeloma cells 551
Genomic abnormalities 552
Interaction between plasma cells and their microenvironment 555
Influence of pathogenesis on the clinical features of MM and the development of bone lesions 556
Differential diagnosis 557
Monoclonal gammopathy of undetermined significance 557
Smouldering multiple myeloma 558
Symptomatic multiple myeloma 558
Other special forms of plasma cell dyscrasia 559
Plasma cell leukaemia 559
Solitary plasmacytoma of bone 559
Extramedullary plasmacytoma 559
Non-secretory multiple myeloma 559
IgM multiple myeloma 559
Osteosclerotic myeloma (POEMS syndrome) 559
Disease complications and their management 560
Bone involvement: assessment and treatment 560
Renal failure 561
Anaemia and bone marrow failure 562
Infection 563
Nervous system involvement 563
Prognostic factors 563
Host factors 563
Malignant clone factors 564
Tumour burden and disease complications 565
Response to therapy as a prognostic factor 565
Treatment 566
Should all myeloma patients be treated? 566
Treatment of newly diagnosed transplant candidate patients 566
Treatment of newly diagnosed elderly and non-transplant candidate patients 569
Treatment at relapse 571
Side-effects associated with novel agents 571
Promising new drugs 573
Acknowledgements 574
Selected bibliography 575
30 Amyloidosis 576
Introduction 576
Pathogenesis of amyloid 576
Systemic AL amyloidosis 577
AL fibrils and monoclonal light chains 578
The plasma cell dyscrasia 578
Clinical features 578
Diagnosis and investigation of AL amyloidosis 579
Differential diagnosis 582
Natural history 582
Management 583
Localized AL amyloidosis 585
Other forms of systemic amyloidosis 586
AA amyloidosis 586
b2-Microglobulin amyloidosis 586
Transthyretin amyloidosis (ATTR amyloidosis) 586
Hereditary systemic amyloidoses 587
Conclusion and future directions 587
Selected bibliography 588
31 The classification of lymphomas: updating the WHO classification 589
Introduction 589
Mature B-cell neoplasms 589
Chronic lymphocytic leukaemia/small lymphocytic lymphoma (see also Chapter 27) 589
B-cell prolymphocytic leukaemia (see also Chapter 27) 591
Splenic marginal zone lymphoma 591
Lymphoplasmacytic lymphoma/Waldenström macroglobulinaemia 592
Plasma cell neoplasms (see also Chapter 29) 592
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) 594
Nodal marginal zone lymphoma (NMZL) 595
Follicular lymphoma (FL) 595
Mantle-cell lymphoma 597
Diffuse large B-cell lymphoma not otherwise specified (see also Chapter 34) 598
T-cellhistiocyte-rich large B-cell lymphoma 600
DLBCL with a predominant extranodal location 600
Large-cell lymphomas of terminally differentiated B cells 601
Burkitt lymphoma 601
B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma 602
B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma 602
Mature NK-cell/T-cell neoplasms (see also Chapter 28) 603
Aggressive NK-cell leukaemia 603
EBV-positive T-cell lymphoproliferative disorders of childhood 604
Adult T-cell leukaemia/lymphoma (see also Chapter 34) 604
Extranodal NKT-cell lymphoma, nasal type (see also Chapter 34) 604
Enteropathy-associated T-cell lymphoma (see also Chapter 28) 605
Hepatosplenic T-cell lymphoma 605
Subcutaneous panniculitis-like T-cell lymphoma 606
Mycosis fungoides and Sézary syndrome (see also Chapter 28) 606
Primary cutaneous CD30-positive T-cell lymphoproliferative disorders 607
Primary cutaneous ???????????? T-cell lymphoma 607
Peripheral T-cell lymphoma not otherwise specified (see also Chapter 28) 608
Angioimmunoblastic T-cell lymphoma 608
Anaplastic large-cell lymphoma, ALK+ 610
Anaplastic large-cell lymphoma, ALK? 612
Hodgkin lymphoma (see also Chapter 32) 613
Nodular lymphocyte-predominant Hodgkin lymphoma 613
Classical Hodgkin lymphoma 614
Selected bibliography 614
32 Hodgkin lymphoma 615
Introduction 615
Pathological features 615
Classification 615
Pathogenesis 615
Histological features 617
Clinical features 618
Presentation 618
Investigation 619
Staging and risk stratification 620
Ann Arbor staging 620
Risk stratification 622
Management 622
Conventional chemotherapy regimens 622
Radiotherapy 622
Novel agents 622
Conventional frontline treatment 623
Early-stage favourable 623
Early-stage unfavourable 624
Advanced-stage disease 624
Risk-adapted frontline treatment 624
Early-stage disease 624
Advanced-stage disease 625
Relapsed/refractory disease 625
Treatment of older patients 626
Late effects 626
Secondary solid organ malignancy 626
Secondary myeloid malignancy 626
Cardiovascular disease 626
Infertility 627
Conclusion 627
Selected bibliography 627
33 Non-Hodgkin lymphoma: low grade 628
Introduction 628
Epidemiology 628
Histology and classification of low-grade NHL 628
Follicular lymphoma 629
Epidemiology of FL 629
Pathology of FL 629
Pathophysiology of FL 630
Clinical features of FL 630
Staging and baseline investigations in FL 631
Predicting prognosis in FL 631
Management of early-stage FL 632
Management of advanced-stage asymptomatic FL 632
First-line management of advanced-stage symptomatic FL 633
Management of relapsed FL 635
Novel therapies for FL 637
Management of transformed FL 637
Suggested algorithm for management of FL 638
Marginal-zone lymphomas 638
MALT lymphoma 638
Splenic marginal-zone lymphoma 639
Nodal marginal-zone lymphoma 640
Waldenström macroglobulinaemia 640
Management of Waldenström macroglobulinaemia 641
Guidelines for management of Waldenström macroglobulinaemia 642
Mantle-cell lymphoma 642
Prognosis in MCL 642
First-line management of MCL 642
Relapsed disease and novel treatments 643
Selected bibliography 643
34 Non-Hodgkin lymphoma: high grade 645
Introduction 645
Epidemiology 645
Classification of high-grade lymphomas 645
Aetiology 645
Molecular basis of lymphomas (see also Chapter 18) 646
Diagnosis 646
Clinical features 646
Laboratory investigations 647
Staging 647
Treatment 647
Particular considerations prior to therapy 648
Diffuse large B-cell lymphoma 648
Aetiology 648
Pathogenesis and molecular basis of DLBCL 648
Prognostic factors 650
Treatment 651
Primary mediastinal (thymic) large B-cell lymphoma 655
Genetic and molecular features 655
Treatment and prognosis 656
Intravascular large B-cell lymphoma 656
Burkitt lymphoma 657
Genetic and molecular features 657
Treatment and prognosis 657
B cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma 658
Transformed lymphomas (see also Chapter 33) 658
Double-hit or triple-hit lymphomas 659
DLBCL in HIV-positive patients 659
Treatment of relapsed/refractory AIDS-related lymphoma 660
Burkitt lymphoma in HIV-positive patients 660
Primary central nervous system lymphoma 660
Diagnosis 660
Genetic and molecular features 660
Treatment 660
Relapsed PCNSL 661
Post-transplant lymphoproliferative disorder 661
CNS prophylaxis in high-grade non-Hodgkin lymphoma 662
Suggested algorithm for therapy of aggressive non-Hodgkin lymphoma (summary) 662
At diagnosis 662
At relapse 662
Rare aggressive T-cell and NK-cell lymphomas (see also Chapter 31) 662
Adult T-cell leukaemia/lymphoma 662
Extranodal NK/T-cell lymphoma, nasal type (see also Chapter 31) 663
Future directions 663
Selected bibliography 663
35 Stem cell transplantation 665
Immunological basis of stem cell transplantation 665
The human leucocyte antigen system 665
HLA matching for transplantation 666
Acute graft-versus-host disease 667
Chronic graft-versus-host disease 667
Graft-versus-leukaemia effect 669
Immune reconstitution 669
Stem cell engraftment 669
Biology of stem cell engraftment 669
Clinical factors determining stem cell engraftment 670
Stem cell mobilization 670
Biology of stem cell trafficking 670
Stem cell mobilization in clinical practice 670
Choice of stem cell source and dose 671
Conditioning regimens: basic principles 672
Conditioning regimens in autologous SCT 673
Myeloablative conditioning regimens in allogeneic SCT 673
Comparison of myeloablative conditioning regimens 674
Strategies for GVHD prophylaxis in myeloablative regimens 675
Reduced-intensity conditioning regimens in malignant and non-malignant disease 675
Strategies for GVHD prophylaxis in RIC regimens 676
Clinical management of patients undergoing stem cell transplantation 676
Practicalities of stem cell infusion and blood product support 676
Complications of allogeneic SCT 677
Complications of autologous SCT 684
Patient factors determining outcome after allogeneic stem cell transplantation 685
Indications for transplantation 685
Factors determining the choice of an allogeneic stem cell donor: the donor algorithm 685
Management of disease relapse 687
Future developments in stem cell transplantation 688
Autologous SCT 688
Allogeneic SCT 688
Selected bibliography 689
36 Normal haemostasis 690
Introduction 690
Overview of haemostasis 690
Tissue factor initiates blood coagulation 692
Amplification of the initial stimulus 692
Feedback inhibition of the procoagulant response 694
Fibrinolysis 695
Blood vessels 696
The endothelium 696
The platelet–vessel wall interaction 696
von Willebrand factor 697
Endothelial cell anticoagulant activities 698
Endothelial cell-derived fibrinolytic factors 698
Coagulation factors 698
Tissue factor 698
Factor VII 698
Factor X 703
Factor IX 703
Factor XI 703
Factor XIII 703
Factor VIII 703
Factor V 704
Fibrinogen 704
Prothrombin 704
Naturally occurring inhibitors of blood coagulation 704
Classification of physiological anticoagulants 704
Tissue factor pathway inhibitor: a Kunitz-type inhibitor 705
Serine protease inhibitors (serpins) and heparin 705
The protein C pathway: inhibition of cofactors FVa and FVIIIa 707
Fibrinolysis 709
Components of the fibrinolytic system 709
Plasminogen and plasmin 709
Action of plasmin on fibrin and fibrinogen 710
Plasminogen activators 710
Inhibitors of fibrinolysis 711
Selected bibliography 712
37 The vascular function of platelets 713
Introduction 713
Platelet structure and organelles 713
Animal models 715
Platelet formation 715
Thrombus formation 715
Platelet capture and stable adhesion 715
Spreading 717
Granule secretion and TxA2 formation 718
Aggregation 718
Thrombus stabilization 718
Procoagulant activity 718
Stimulatory receptors and their signalling pathways 719
Tyrosine kinase-linked receptors 719
G-protein-coupled receptors 721
Other platelet receptors and their ligands 722
Second messenger pathways underlying activation 723
Calcium 723
Protein kinase C 723
Phosphatidylinositol 3-kinase 724
The molecular basis of platelet activation 724
Stable adhesion and aggregation 724
Secretion 724
TxA2 formation 724
Actin polymerization 724
Inhibitory agonists and their receptors 725
Platelet-based bleeding problems 725
Platelet function testing 725
Platelets and thrombosis 727
Genetics of platelet function disorders 727
Conclusions and future developments 728
Acknowledgements 728
Selected bibliography 728
38 Haemophilia and Von Willebrand Disease 729
Introduction 729
Haemophilia 729
Pathophysiology of haemophilia 729
Clinical features 729
Presentation 731
Investigation of coagulation defects and haemophilia 731
Laboratory diagnosis of haemophilia 732
Treatment 732
Complications of therapy 735
Molecular genetics of haemophilia A 736
Molecular genetics of haemophilia B 736
Gene therapy for haemophilia 737
Haemophilia A and B in females 738
General organization of haemophilia care 739
Acquired haemophilia 739
von Willebrand disease 739
von Willebrand factor (VWF) 739
Clinical features 740
Laboratory diagnosis 741
Treatment 744
Clinical course and complications 745
Molecular genetics 745
Pseudo von Willebrand disease (platelet-type) 745
Acquired von Willebrand syndrome 746
Selected bibliography 746
39 Rare inherited coagulation disorders 747
Introduction 747
Clinical symptoms 747
Classification 747
Laboratory diagnosis 748
Molecular diagnosis 751
Global haemostasis tests 751
Treatment 751
Fibrinogen deficiency 752
Prothrombin deficiency 752
Factor V deficiency 752
Combined deficiency of factor V and factor VIII 753
Factor VII deficiency 753
Factor X deficiency 754
Factor XI deficiency 754
Factor XIII deficiency 755
Vitamin-K-dependent coagulation factors deficiency 755
Concluding remarks 756
Acknowledgements 756
Selected bibliography 756
40 Acquired coagulation disorders 757
Introduction 757
Tests of coagulation and point-of-care testing 757
Routine tests of haemostasis 757
Disseminated intravascular coagulation 758
Pathophysiology 759
Clinical features 761
Diagnosis 761
Treatment 762
Haemostatic dysfunction in acute promyelocytic leukaemia 762
Vitamin K and related disorders 763
Vitamin K metabolism 763
Vitamin K deficiency 763
Haemostatic disturbance in liver disease (Figure 40.5) 764
Acute hepatitis 764
Chronic liver disease 765
Liver transplantation 766
Hypercoagulability in liver disease 766
Haemostatic disturbance in renal disease 767
Pregnancy-related haemostatic dysfunction 767
Haemostatic dysfunction associated with cardiopulmonary bypass surgery 768
Haemostatic dysfunction associated with trauma 768
Coagulopathy in massive blood loss 769
Bruising 769
Purpura simplex (normal easy bruising) 769
Non-accidental bruising 769
Senile purpura (atrophic or actinic purpura) and steroid-related purpura 769
Painful bruising syndrome (psychogenic purpura) 770
Scurvy 770
Inherited disorders of collagen and elastic fibres 770
Haemostatic dysfunction associated with vasculitis 770
Arteriovenous malformations 770
Hereditary haemorrhagic telangiectasia 770
Kasabach–Merritt syndrome 771
Microthromboembolic disease 771
Cholesterol embolism 771
Fat embolism syndrome 771
Warfarin-induced skin necrosis 771
Haemostatic dysfunction associated with paraproteinaemia and amyloidosis 771
Paraproteinaemia 771
Amyloidosis 772
Acquired inhibitors of coagulation factors 772
Acquired haemophilia A 772
Acquired von Willebrand syndrome 774
Acquired factor V deficiency 774
Acquired protein S deficiency 774
Prothrombin deficiency associated with lupus anticoagulant 774
Selected bibliography 774
41 Congenital platelet disorders 775
Introduction 775
Thrombocytopenias 776
Non-inherited congenital thrombocytopenia 776
Inherited thrombocytopenias 777
Inherited thrombocytopenias with increased platelet size 778
Thrombocytopathies 780
Disorders of platelet adhesion 780
Disorders of platelet signalling transduction 781
Disorders of platelet aggregation 781
Treatment 783
General measures 783
Drugs 783
Platelet transfusions 785
Other measures 785
Conclusions 785
Selected bibliography 785
42 Primary immune thrombocytopenia 787
Introduction 787
Clinical features 787
Reaching a consensus on terminology 787
Pathophysiology 788
ITP is multifactorial 788
Antiplatelet antibodies and their targets 788
The role of Helicobacter pylori in the development of ITP 789
T cells may also be involved 789
Thrombopoietin levels in ITP 789
Natural history of ITP 790
Diagnosis 790
Bone marrow examination 791
Management 791
Splenectomy 792
Short-term treatment 792
Long-term treatment 792
Patients with refractory ITP 793
Is drug treatment needed? 793
Rituximab 793
Combination chemotherapy 793
TPO receptor agonists 793
ITP in children 794
‘Watch and wait policy 794
General measures for persistent and chronic ITP in children 794
Treatment options in childhood ITP 794
ITP in pregnancy (see also Chapter 50) 795
Laboratory investigation of ITP in pregnancy 795
Management of ITP in pregnancy 795
Delivery 795
Treatment options in pregnancy 795
Selected bibliography 796
43 Thrombotic thrombocytopenic purpura and haemolytic–uraemic syndrome (congenital and acquired) 797
Historical introduction 797
Thrombotic thrombocytopenic purpura 798
Pathology and pathogenesis 799
Clinical and laboratory findings 800
Differential diagnosis with HUS 801
Differential diagnosis with other thrombotic microangiopathies 802
Natural history 802
Treatment 802
Haemolytic uraemic syndrome 804
STEC-HUS 804
Atypical HUS 805
Concluding remarks 808
Selected bibliography 808
44 Heritable thrombophilia 809
Introduction 809
Heritable thrombophilias associated with venous thrombosis 809
Antithrombin deficiency 811
Protein C deficiency 813
Protein S deficiency 814
FVR506Q (FV) 814
F2G20210A 814
Genome-wide association studies (GWAS) and deep sequencing of candidate genes 815
Other natural anticoagulants 815
Other procoagulant factors 815
Fibrinolysis 816
Homocysteine 816
Treatment of patients with venous thrombosis and heritable thrombophilias 816
Case finding 817
Prevention of thrombosis associated with oestrogen-containing hormone preparations 817
Prevention of pregnancy-associated venous thrombosis 818
Pregnancy morbidity 818
Purpura fulminans 818
Vitamin K antagonist-induced skin necrosis 818
Thrombophilia and arterial thrombosis 818
Neonatal stroke (see also Chapter 50) 819
Laboratory methodology and testing strategy 819
Preanalytical variables 819
General recommendations for laboratory tests and interpretation 820
Antithrombin assays 820
Protein C assays 820
Protein S assays 821
FVR506Q and APC resistance 821
F2G20210A 821
Next-generation global thrombophilia tests 821
Counselling and genetic testing 821
Selected bibliography 822
45 Acquired venous thrombosis 823
Epidemiology of venous thromboembolism (VTE) 823
Pregnancy and venous thromboembolism 823
Immobility as a risk factor for venous thromboembolism 824
Iatrogenic venous thromboembolism 825
Hospital acquired thrombosis 825
Indwelling venous devices 825
Pharmaceuticals 825
Antiphospholipid syndrome 827
Antiphospholipid antibodies 827
Pathogenic mechanisms in APS 828
Laboratory diagnosis of antiphospholipid antibodies 828
Management of APS 830
Venous thromboembolism and cancer 830
Thrombotic risk in myeloproliferative disease (polycythaemia rubra vera and essential thrombocythaemia) (see also Chapter 26) 831
Acute promyelocytic leukaemia 832
Inflammation and thrombosis 832
Haematological prothrombotic states due to non-malignant diseases of the blood and bone marrow 832
Paroxysmal nocturnal haemoglobinuria (see Chapter 11) 832
Thrombotic thrombocytopenic purpura 833
Sickle cell disease (see Chapter 7) 833
Selected bibliography 833
46 Antithrombotic agents 834
Heparins 834
Danaparoid 835
Direct thrombin inhibitors 835
Bivalirudin 835
Argatroban 835
Vitamin K antagonists (VKA) 835
Non-vitamin K antagonist oral anticoagulants (NOACs) 837
Dabigatran 839
Rivaroxaban 839
Apixaban 840
Edoxaban 840
Measurement of anticoagulant effect of NOACs 840
Interruption of anticoagulant treatment and switching with other anticoagulant drugs 840
Management of bleeding patients treated with NOACs 841
Antiplatelet drugs 841
Aspirin 841
Dipyridamole 842
Clopidogrel, prasugrel and ticagrelor 842
Abciximab, eptifabatide and tirofiban 842
Selected bibliography 843
47 Management of venous thromboembolism 844
Introduction 844
Diagnosis of deep vein thrombosis 844
Isolated calf DVT 844
Algorithms for the diagnosis of a deep vein thrombosis 845
Diagnosis of pulmonary embolism 845
Treatment of VTE 845
Initial anticoagulant therapy 846
Thrombolytic therapy 847
Long-term complications of VTE 848
Post-thrombotic syndrome (PTS) 848
Chronic thromboembolic pulmonary hypertension (CTPH) 848
Risk of recurrence and duration of anticoagulant therapy 848
Other treatments 849
Vena caval filters 849
Thrombectomy 850
Venous thrombosis in unusual sites 850
Cerebral vein thrombosis 850
Retinal vein thrombosis 850
Upper limb DVT 850
Intra-abdominal vein thrombosis 850
Superficial thrombophlebitis 851
Selected bibliography 851
48 Haematological aspects of systemic disease 852
Anaemia of chronic disease 852
Pathogenesis 852
Treatment 853
Malignancy 853
Anaemia 853
Haemolysis 853
Red cell aplasia 854
Leucoerythroblastic anaemia 854
Other causes of anaemia 854
Treatment 855
Polycythaemia 855
White cells (Table 48.4) 855
Platelets 855
Coagulation (Table 48.6) 856
Connective tissue disorders (Table 48.8) 857
Anaemia 857
White cells 857
Platelets 857
Coagulation 858
Other changes 858
Renal disease (Table 48.9) 858
Anaemia 858
Polycythaemia 859
Haemostatic abnormalities 859
Endocrine disease (Table 48.10) 859
Liver disease (Table 48.11) 860
Anaemia 860
Platelets and haemostasis 860
Liver transplantation 860
Congestive Heart Failure (CHF) 861
Infections (Tables 48.12 and 48.13) 861
Viruses 861
Bacterial, fungal and protozoal infections 862
Haemophagocytic lymphohistiocytosis (haemophagocytic syndrome) (Table 48.14 see also Chapters 14)
Haematological aspects of pregnancy (Table 48.15) 864
Anaemia 864
White cells 865
Platelets 865
Coagulation changes 865
Anaemia in the elderly 865
Haematological aspects of HIV infection (Table 48.16) 865
Pathophysiology 866
Anaemia 866
White cells 866
Platelets 866
Coagulation 866
Other changes 866
Selected bibliography 866
49 Haematological aspects of tropical diseases 868
Introduction 868
Ethnic variations in reference ranges 868
Tropical diseases with organisms in peripheral blood or bone marrow 868
Malaria 868
Filariasis 875
African trypanosomiasis (sleeping sickness) 877
American trypanosomiasis (Chagas disease) 879
Leishmaniasis 879
Tropical diseases associated with changes in FBC and or coagulation 881
Hookworm infection 881
Schistosomiases (Bilharzia) 881
Viral haemorrhagic fevers 881
Non-specific haematological abnormalities associated with tropical diseases 882
Anaemia 882
White cell abnormalities 882
Platelet abnormalities 882
Hypersplenism 882
Selected bibliography 883
50 Neonatal haematology 884
Developmental haemopoiesis 884
Neonatal anaemia 884
Definition and pathophysiology 884
Causes of neonatal anaemia 885
Anaemia of prematurity 891
Indications for red cell transfusion in neonatal anaemia 892
A simple diagnostic approach to neonatal anaemia 892
Neonatal polycythaemia 892
White cell disorders 892
Normal values 892
Neutropenia 893
Haemostasis and thrombosis in the newborn 894
Developmental haemostasis 894
Screening tests for bleeding disorders 895
Inherited coagulation disorders (see also Chapters 38 and 39) 895
Acquired disorders of coagulation 895
Neonatal thrombocytopenia 896
Neonatal thrombosis: physiology and developmental aspects 897
Screening tests for thrombophilia in neonates 897
Inherited thrombotic disorders in neonates 898
Acquired thrombotic problems in neonates 898
Selected bibliography 898
51 WHO Classification: Tumours of the Haematopoietic and Lymphoid Tissues (2008) 899
Myeloproliferative neoplasms 899
Myelodysplastic/myeloproliferative neoplasms 899
Myelodysplastic syndromes 899
Acute myeloid leukaemia 899
Precursor lymphoid neoplasms 900
Mature B-cell neoplasms 900
Mature T-cell and NK-cell neoplasms 900
Hodgkin lymphoma 901
Histiocytic and dendritic cell neoplasms 901
Post-transplant lymphoproliferative disorders 901
Index 902
EULA 949

Produkt-Details

• Erscheint lt. Verlag: 28.10.2015
• Sprache: englisch
• Themenwelt: Medizinische Fachgebiete ► Innere Medizin ► Hämatologie
• Themenwelt: Studium ► 2. Studienabschnitt (Klinik) ► Pathologie
• Schlagworte: Blood • Book • concise • Continues • Examination • Hämatologie • Haematology • haematology discusses • Hämatologie • Hematology • Key • Knowledge • Marrow • Medical Science • Medizin • needs • pathogenesis • postgraduate • Practice • Preparation • Range • Reader • Residents • resource • Style • Textbook • Trainees • uptodate • wide
• ISBN-10: 1-118-85447-0 / 1118854470
• ISBN-13: 978-1-118-85447-1 / 9781118854471