Hoffbrand’s Essential Haematology
Contents
Preface to the Seventh Edition
Preface to the First Edition
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CHAPTER 1 Haemopoiesis
Site of haemopoiesis
Haemopoietic stem and progenitor cells
Table 1.1 Sites of haemopoiesis.
Figure 1.2 Diagrammatic representation of the bone marrow pluripotent stem cell and the cell lines that arise from it. Various progenitorcells can be identified by culture in semi‐solid medium by the type of colony they form. It is possible that an erythroid/megakaryocyticprogenitor may be formed before the common lymphoid progenitor diverges from the mixed granulocytic/monocyte/eosinophil myeloidprogenitor. Baso, basophil; BFU, burst‐forming unit; CFU, colony‐forming unit; E, erythroid; Eo, eosinophil; GEMM, granulocyte, erythroid,monocyte and megakaryocyte; GM, granulocyte, monocyte; Meg, megakaryocyte; NK, natural killer.
Figure 1.3 (a) Bone marrow cells are increasingly differentiated and lose the capacity for self‐renewal as they mature. (b) A single stemcell gives rise, after multiple cell divisions (shown by vertical lines), to >106 mature cells.
Bone marrow stroma
The regulation of haemopoiesis
Haemopoietic growth factors
Figure 1.4 Haemopoiesis occurs in a suitable microenvironment(‘niche’) provided by a stromal matrix on which stem cells growand divide. The niche may be vascular (lined by endothelium) orendosteal (lined by osteoblasts). There are specific recognitionand adhesion sites (see p. 8); extracellular glycoproteins and othercompounds are involved in the binding.
Figure 1.5 Growth factors may stimulate proliferation of early bone marrow cells, direct differentiation to one or other cell type, stimulatecell maturation, suppress apoptosis or affect the function of mature non‐dividing cells, as illustrated here for granulocyte colony‐stimulatingfactor (G‐CSF) for an early myeloid progenitor and a neutrophil.
Growth factor receptors and signal transduction
Adhesion molecules
The cell cycle
Transcription factors
Epigenetics
Apoptosis
CHAPTER 2 Erythropoiesis and general aspects of anaemia
Blood cells
Erythropoietin
Indications for erythropoietin therapy
Haemoglobin
Haemoglobin synthesis
Haemoglobin function
Methaemoglobinaemia
The red cell
Red cell metabolism
Red cell membrane
Anaemia
Global incidence
Clinical features of anaemia
Classification and laboratory findings in anaemia
Assessment of erythropoiesis
CHAPTER 3 Hypochromic anaemias
Nutritional and metabolic aspects of iron
Body iron distribution and transport
Dietary iron
Iron absorption
Iron requirements
Iron deficiency
Clinical features
Causes of iron deficiency
Laboratory findings
Investigation of the cause of iron deficiency (Fig. 3.12)
Treatment
Iron refractory iron deficency anaemia (IRIDA)
Anaemia of chronic disorders
Sideroblastic anaemia
Lead poisoning
Differential diagnosis of hypochromic anaemia
CHAPTER 4 Iron overload
Assessment of iron status and organ function
Hereditary haemochromatosis
African iron overload
Thalassaemia intermedia
Transfusional iron overload
Iron chelation therapy
CHAPTER 5 Megaloblastic anaemias and other macrocytic anaemias
Introduction to macrocytic anaemia
Megaloblastic anaemias
Vitamin B12 (B12, cobalamin)
Absorption
Transport: the transcobalamins
Biochemical function
Folate
Absorption, transport and function
Biochemical basis for megaloblastic anaemia (Fig. 5.5)
Folate reduction
Vitamin B12 deficiency
Pernicious anaemia (PA)
Other causes of vitamin B12 deficiency
Folate deficiency
Clinical features of megaloblastic anaemia
Vitamin B12 neuropathy (subacute combined degeneration of the cord)
Neural tube defect
Other tissue abnormalities
Laboratory findings
Diagnosis of vitamin B12 or folate deficiency
Tests for cause of vitamin B12 or folate deficiency
Treatment
Response to therapy
Other megaloblastic anaemias
Abnormalities of vitamin B12 or folate metabolism
Other macrocytic anaemias
Differential diagnosis of macrocytic anaemias
CHAPTER 6 Haemolytic anaemias
Normal red cell destruction
Introduction to haemolytic anaemias
Classification
Clinical features
Laboratory findings
Intravascular and extravascular haemolysis
Hereditary haemolytic anaemias
Membrane defects
Defective red cell metabolism
Hereditary disorders of haemoglobin synthesis
Acquired haemolytic anaemias
Immune haemolytic anaemias
Red cell fragmentation syndromes
March haemoglobinuria
Infections
Chemical and physical agents
Secondary haemolytic anaemias
CHAPTER 7 Genetic disorders of haemoglobin
Haemoglobin synthesis
Molecular aspects
Switch from fetal to adult haemoglobin
Haemoglobin abnormalities
Thalassaemias
α‐Thalassaemia syndromes
β‐Thalassaemia syndromes
Non‐transfusion dependent thalassaemia (thalassaemia intermedia)
δβ‐Thalassaemia
Haemoglobin Lepore
Hereditary persistence of fetal haemoglobin
Association of β‐thalassaemia trait with other genetic disorders of haemoglobin
Sickle cell anaemia
Homozygous disease
Clinical features
Sickle cell trait
Combination of haemoglobin S with other genetic defects of haemoglobin
Prenatal diagnosis of genetic haemoglobin disorders
DNA diagnosis
CHAPTER 8 The white cells 1: granulocytes, monocytes and their benign disorders
Granulocytes
Neutrophil (polymorph)
Neutrophil precursors
Monocytes
Eosinophils
Basophils
Granulopoiesis
Control of granulopoiesis: myeloid growth factors
Clinical applications of G‐CSF
Monocytes
Disorders of neutrophil and monocyte function
Chemotaxis (cell mobilization and migration)
Phagocytosis
Killing and digestion
Benign disorders
Other rare disorders
Common morphological abnormalities
Causes of neutrophil leucocytosis
The leukaemoid reaction
Leucoerythroblastic reaction
Neutropenia
Benign ethnic neutropenia
Congenital neutropenia
Drug‐induced neutropenia
Cyclical neutropenia
Autoimmune neutropenia
Idiopathic benign neutropenia
Diagnosis
Management
Causes of monocytosis, eosinophil and basophil leucocytosis
Monocytosis
Eosinophilic leucocytosis (eosinophilia)
Basophil leucocytosis (basophilia)
Histiocytic and dendritic cell disorders
Dendritic cells
Langerhans’ cell histiocytosis
Haemophagocytic lymphohistiocytosis (haemophagocytic syndrome)
Sinus histiocytosis with massive lymphadenopathy
Lysosomal storage diseases
Gaucher’s disease
Niemann–Pick disease
CHAPTER 9 The white cells 2: lymphocytes and their benign disorders
Lymphocytes
B and T lymphocytes
Natural killer cells
Lymphocyte circulation
Immunoglobulins
Antigen–receptor gene rearrangements
Immunoglobulin gene rearrangements
T‐cell receptor gene rearrangements
Complement
The immune response
Lymphocytosis
Infectious mononucleosis
Lymphopenia
Immunodeficiency
Differential diagnosis of lymphadenopathy
CHAPTER 10 The spleen
The anatomy and circulation of the spleen
The functions of the spleen
Control of red cell integrity
Immune function
Extramedullary haemopoiesis
Imaging the spleen
Splenomegaly
Tropical splenomegaly syndrome
Hypersplenism
Hyposplenism
Splenectomy
Prevention of infection in hyposplenic patients
CHAPTER 11 The aetiology and genetics of haematological malignancies
The incidence of haematological neoplasms
The aetiology of haemopoietic malignancy
Inherited factors
Environmental influences
Infection
The genetics of haemopoietic malignancy
Oncogenes
Tyrosine kinases
Tumour‐suppressor genes
Clonal progression
Progression of subclinical clonal haematological abnormalities to clinical disease
Chromosome nomenclature
Telomeres
Specific examples of genetic abnormalities in haematological malignancies
Point mutation
Translocations
Deletions
Duplication or amplification
Epigenetic alterations
MicroRNAs
Diagnostic methods used to study malignant cells
Karyotype analysis
Fluorescence in situ hybridization analysis
Gene sequencing
DNA microarray platforms
Flow cytometry
Immunohistology (immunocytochemistry)
Value of genetic markers in management of haematological malignancy
Initial diagnosis
For establishing a treatment protocol
Monitoring the response to therapy
CHAPTER 12 Management of haematological malignancy
General support therapy
Insertion of a central venous catheter
Blood product support
Haemostasis support
Anti‐emetic therapy
Tumour lysis syndrome
Psychological support
Reproductive issues
Nutritional support
Pain
Prophylaxis and treatment of infection
Bacterial infection
Viral infection
Fungal infection
Specific therapies for haematological malignancy
Drugs used in the treatment of haemopoietic malignancies
CHAPTER 13 Acute myeloid leukaemia
Classification of leukaemia
Diagnosis of acute leukaemia
Acute myeloid leukaemia
Pathogenesis
Incidence
Classification
Clinical features
Investigations
Cytogenetics and molecular genetics
Treatment
Outcome
CHAPTER 14 Chronic myeloid leukaemia
Chronic myeloid leukaemia
Clinical features
Laboratory findings
Prognostic scores (stages)
Treatment
Chronic neutrophilic leukaemia
Chronic eosinophilic leukaemia
CHAPTER 15 Myeloproliferative disease
Polycythaemia
Classification of polycythaemia
Primary polycythaemia (erythrocytosis)
Congenital
Acquired
Polycythaemia vera (PV)
Diagnosis
Clinical features
Laboratory findings
Treatment
Course and prognosis
Congenital causes of primary polycythaemia
Secondary polycythaemia
Apparent polycythaemia
Differential diagnosis of polycythaemia
Essential thrombocythaemia
Diagnosis
Clinical and laboratory findings
Prognosis and treatment
Course
Primary myelofibrosis
Clinical features
Laboratory findings
Treatment
Mastocytosis
CHAPTER 16 Myelodysplasia
Myelodysplasia (myelodysplasticsyndromes, MDS)
Pathogenesis
Classification
Clinical features
Laboratory findings
Treatment
Myelodysplastic/myeloproliferative neoplasms
Chronic myelomonocytic leukaemia
Atypical chronic myeloid leukaemia
Juvenile myelomonocytic leukaemia (JMML)
CHAPTER 17 Acute lymphoblastic leukaemia
Incidence and pathogenesis
Classification
Clinical features
Bone marrow failure
Organ infiltration
Investigations
Cytogenetics and molecular genetics
Treatment
General supportive therapy
Specific therapy of ALL in children
Minimal residual disease
Remission induction
Intensification (consolidation)
Central nervous system‐directed therapy
Maintenance
Treatment of relapse
Toxicity
Specific therapy of ALL in adults
Treatment of BCR‐ABL1 positive ALL
Prognosis
CHAPTER 18 The chronic lymphoid leukaemias
Diagnosis
B‐cell diseases
Chronic lymphocytic leukaemia
B‐cell prolymphocytic leukaemia
Hairy cell leukaemia
Lymphocytosis in non‐Hodgkin lymphomas
T‐cell diseases
T‐cell prolymphocytic leukaemia
Large granular lymphocytic leukaemia
Adult T‐cell leukaemia/lymphoma
CHAPTER 19 Hodgkin lymphoma
History and pathogenesis
Clinical features
Haematological and biochemical findings
Diagnosis and histological classification
Clinical staging
Positron emission tomography (PET)
Treatment
Early stage disease
Advanced stage disease
Assessment of response to treatment
Relapsed cases
Prognosis
The late effects of Hodgkin lymphoma and its treatment
CHAPTER 20 Non-Hodgkin lymphoma
Introduction to non-Hodgkin lymphoma
Classification
Low- and high-grade non-Hodgkin lymphoma
Pathogenesis
Clinical features of non-Hodgkin lymphoma
Investigations
Staging
General principles of treatment of non-Hodgkin lymphoma
Specific subtypes of non-Hodgkin lymphoma
Low-grade non-Hodgkin lymphoma
High-grade non-Hodgkin lymphoma
T-cell lymphomas
Peripheral T-cell non-Hodgkin lymphoma, unspecified
Angioimmunoblastic lymphadenopathy
Mycosis fungoides
Sézary syndrome
Adult T-cell leukaemia/lymphoma
Enteropathy-associated T-cell lymphomas
Anaplastic large cell lymphoma
Histiocytic and dendritic cell neoplasms
CHAPTER 21 Multiple myeloma and related disorders
Paraproteinaemia
Multiple myeloma
Pathogenesis
Smouldering myeloma
Diagnosis
Clinical features
Treatment
Prognosis
Other plasma cell tumours
Solitary plasmacytoma
Plasma cell leukaemia
Osteosclerotic myeloma (POEMS syndrome)
Monoclonal gammopathy of undetermined significance
Amyloidosis
Systemic AL amyloidosis
Hyperviscosity syndrome
CHAPTER 22 Aplastic anaemia and bone marrow failure
Pancytopenia
Aplastic anaemia
Pathogenesis
Congenital: Fanconi anaemia (FA)
Idiopathic acquired aplastic anaemia
Paroxysmal nocturnal haemoglobinuria (PNH)
Red cell aplasia
Chronic form
Transient form
Schwachman–Diamond syndrome
Congenital dyserythropoietic anaemia
Osteopetrosis
CHAPTER 23 Stem cell transplantation
Principles of stem cell transplantation
Collection of stem cells
Stem cell processing
Conditioning
Post-transplant engraftment and immunity
Autologous stem cell transplantation
Allogeneic stem cell transplantation
The human leucocyte antigen (HLA) system
Human leucocyte antigen and transplantation
Chimaerism analysis
Complications
Graft-versus-leukaemia effect and donor leucocyte infusions
Post-transplant lymphoproliferative diseases
CHAPTER 24 Platelets, blood coagulation and haemostasis
Platelets
Platelet production
Platelet structure
Platelet antigens
Platelet function
Blood coagulation
The coagulation cascade
Coagulation in vivo
Endothelial cells
Haemostatic response
Vasoconstriction
Platelet reactions and primary haemostatic plug formation
Stabilization of the platelet plug by fibrin
Physiological limitation of blood coagulation
Fibrinolysis
Inactivation of plasmin
Tests of haemostatic function
Blood count and blood film examination
Screening tests of blood coagulation
Specific assays of coagulation factors
Bleeding time
Tests of platelet function
Tests of fibrinolysis
CHAPTER 25 Bleeding disorders caused by vascular and platelet abnormalities
Abnormal bleeding
Vascular bleeding disorders
Inherited vascular disorders
Acquired vascular defects
Thrombocytopenia
Failure of platelet production
Increased destruction of platelets
Disorders of platelet function
Hereditary disorders
Acquired disorders
Diagnosis of platelet disorders
Thrombomimetics
Platelet transfusions
CHAPTER 26 Coagulation disorders
Hereditary coagulation disorders
Haemophilia A
Factor IX deficiency (haemophilia B, Christmas disease)
Von Willebrand disease
Hereditary deficiency of other coagulation factors
Acquired coagulation disorders
Vitamin K deficiency
Liver disease
Disseminated intravascular coagulation
Coagulation deficiency caused by antibodies
Massive transfusion syndrome
Thromboelastography: near‐patient testing
CHAPTER 27 Thrombosis 1: pathogenesis and diagnosis
Arterial thrombosis
Pathogenesis
Clinical risk factors
Venous thrombosis
Pathogenesis and risk factors
Hereditary disorders of haemostasis
Acquired risk factors
Investigation of thrombophilia
Diagnosis of venous thrombosis
Deep vein thrombosis
Pulmonary embolus
CHAPTER 28 Thrombosis 2: treatment
Anticoagulant drugs
Heparin
Mode of action
Indications
Administration and laboratory control
Direct‐acting parenteral anticoagulants
Oral anticoagulants
Principles of oral anticoagulation with VKAs
Drug interactions
Management of warfarin overdose
Management of surgery: bridging anticoagulation
Direct acting oral anticoagulants
Post‐thrombotic syndrome
Mechanical methods of prophylaxis of DVT and PE
Graduated compression stockings
Intermittent compression devices
Inferior vena cava filter
Fibrinolytic agents
Antiplatelet drugs
CHAPTER 29 Haematological changes in systemic diseases
Anaemia of chronic disorders (ACD)
Haematological problems in the elderly
Anaemia
Thrombosis
Malignant diseases (other than primary bone marrow diseases)
Anaemia
Polycythaemia
White cell changes
Platelet and blood coagulation abnormalities
Rheumatoid arthritis (and other connective tissue disorders)
Renal failure
Anaemia
Platelet and coagulation abnormalities
Congestive heart failure
Liver disease
Hypothyroidism
Infections
Bacterial infections
Viral infections
Malaria
Toxoplasmosis
Kala‐azar (visceral leishmaniasis)
Other parasitic diseases
Osteopetrosis
Non‐specific monitoring of systemic disease
Erythrocyte sedimentation rate
Plasma viscosity
C‐reactive protein
CHAPTER 30 Blood transfusion
Blood donor
Red cell antigens and blood group antibodies
Blood group antibodies
ABO system
Rh system
Other blood group systems
Hazards of allogeneic blood transfusion
Infection
Techniques in blood group serology
Cross‐matching and pre‐transfusion tests
From the patient
From the donor
The cross‐match
Electronic cross‐match
Complications of blood transfusion
Haemolytic transfusion reactions
Other transfusion reactions
Reduction of blood product use
Blood components
Leucodepletion
Red cells
Autologous donation and transfusion
Granulocyte concentrates
Platelet concentrates
Preparations from human plasma
Fresh frozen plasma (FFP)
Human albumin solution (4.5%)
Human albumin solution (20%) (salt‐poor albumin)
Cryoprecipitate
Freeze‐dried factor VIII concentrates
Freeze‐dried factor IX–prothrombin complex concentrates
Protein C concentrate
Immunoglobulin
Specific immunoglobulin
Acute blood loss and massive haemorrhage
CHAPTER 31 Pregnancy and neonatal haematology
Haematology of pregnancy
Physiological anaemia
Iron deficiency anaemia
Folate and vitamin B12 deficiency
Thrombocytopenia
Haemostasis and thrombosis
Treatment of thrombosis
Neonatal haematology
Normal blood count
Anaemia in the neonate
Anaemia of prematurity
Neonatal polycythaemia
Fetomaternal alloimmune thrombocytopenia
Coagulation
Haemolytic disease of the newborn
Rh haemolytic disease of the newborn
ABO haemolytic disease of the newborn
Appendix: World Health Organization classification of tumours of the haematopoietic and lymphoid tissues
Myeloproliferative neoplasms
Myelodysplastic/myeloproliferative neoplasms
Myelodysplastic syndromes
Acute myeloid leukaemia
Precursor lymphoid neoplasms
Mature B‐cell neoplasms
Mature T‐cell and NK‐cell neoplasms
Hodgkin lymphoma
Histiocytic and dendritic cell neoplasms
Post‐transplant lymphoproliferative disorders
Index
EULA