Table of Contents
Cover
Title Page
Copyright
Preface
About the companion website
Chapter 1: An introduction to haematopoiesis
Where is blood formed?
Haematopoietic stem cells
Differentiating blood cells
Myelopoiesis
Lymphopoiesis
Summary
Chapter 2: Anaemia: General principles
Anaemia
Symptoms and signs of anaemia
Normal control of red cell production
Morphological classification of anaemias
Microcytic anaemia: iron handling and iron deficiency anaemia
Normocytic anaemia
Macrocytic anaemia
Polycythaemia (erythrocytosis)
Chapter 3: Haemolytic anaemias
Laboratory evidence of haemolysis
Clinical features of haemolysis
Classifying haemolytic anaemias and establishing a diagnosis
Congenital haemolytic anaemias
Acquired haemolytic anaemias
Chapter 4: Disorders of globin synthesis
Normal structure and function of haemoglobin
Thalassaemia
Structural haemoglobin variants
Chapter 5: Conditions associated with white cell abnormalities
Leucopenia
Leucocytosis
Lymphocytosis and lymphopenia
Immunophenotyping by flow cytometry
Infectious mononucleosis
Leucoerythroblastic reaction
Chapter 6: Structure and function of lymphoid tissue
Lymph node structure
Immunoglobulin structure and gene rearrangement
Natural killer cells
Cellular origin of lymphomas
Chapter 7: Lymphomas: General principles
Lymphomas versus leukaemias
Lymphomas
Chapter 8: Classification of lymphoma
Chapter 9: Neoplastic disorders of lymphoid cells
Hodgkin lymphoma
Non-Hodgkin lymphomas
Chapter 10: Plasma cell myeloma and other paraproteinaemias
Plasma cell myeloma
Other paraproteinaemias and related disorders
Chapter 11: Neoplastic disorders of myeloid cells
Acute myeloid leukaemia
The myelodysplastic syndromes
Myeloproliferative disorders
Chapter 12: Bone marrow transplantation
Allogeneic bone marrow transplantation
Graft-versus-leukaemia/lymphoma effect
Reduced intensity conditioning transplant
Haploidentical bone marrow transplantation
Autologous bone marrow transplantation (high-dose therapy)
Chapter 13: Aplastic anaemia and pure red cell aplasia
Aplastic anaemia
Pure red cell aplasia
Chapter 14: Haemostasis, abnormal bleeding and anticoagulant therapy
Normal haemostasis
Classification of haemostatic defects
Platelets
Thrombocytopenic and non-thrombocytopenic purpura
Causes of thrombocytopenia
Abnormalities of platelet function
Platelet transfusions
Normal coagulation mechanism
The fibrinolytic mechanism
Tests for clotting defects
Congenital coagulation disorders
Acquired coagulation disorders
Anticoagulant drugs
Investigation of a patient with abnormal bleeding
Natural anticoagulant mechanisms and the prothrombotic state (thrombophilia)
Chapter 15: Blood groups and blood transfusion
Blood transfusion and blood components
Transfusing red blood cells
Haemolytic disease of the newborn
Other blood components: platelets, plasma and granulocytes
Hazards of blood transfusion: The SHOT report
Management of transfusion reactions
Massive transfusion
Chapter 16: Cellular and molecular investigations in haematology
Immunophenotyping
Cytogenetics and fluorescence in situ hybridization
Molecular genetics
An integrated haematology laboratory report
Personalized medicine?
Index
End User License Agreement
Pages
vii
ix
1
2
3
4
5
6
7
8
9
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
81
82
83
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
125
126
127
128
129
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
173
174
175
176
177
Guide
Cover
Table of Contents
Preface
Begin Reading
List of Illustrations
Chapter 1: An introduction to haematopoiesis
Figure 1.1 A schematic representation of the process of haematopoiesis. Multipotent stem cells give rise to lymphoid (pink) and myeloid (blue) lineages. The myeloid lineage further divides into granulocytic, erythroid and megakaryocytic (platelet) lineages. As cells progress through this process of differentiation, they accrue more functional specialization and lose their multipotency. GMP, granulocyte macrophage progenitor; HSC, haematopoietic stem cell; MEP, megakaryocyte/erythroid progenitor; NK, natural killer.
Figure 1.2 Neutrophil precursors from normal bone marrow. (a) Myeloblast (arrowed); the other nucleated cells near the myeloblast are an eosinophil granulocyte (centre) and two polychromatic erythroblasts. (b) Promyelocyte (arrowed); the other nucleated cells are two polychromatic erythroblasts and a neutrophil metamyelocyte. (c) Neutrophil myelocyte (arrowed); there are two neutrophil band cells adjacent to the myelocyte.
Figure 1.3 Monocyte and two neutrophil granulocytes – the monocyte has a pale, greyish-blue vacuolated cytoplasm.
Figure 1.4 Mature megakaryocyte (centre). This is a very large cell with a single lobulated nucleus. Compare the size of the megakaryocyte with that of the other nucleated marrow cells in this figure.
Figure 1.5 (a) Proerythroblast, (b) basophilic normoblast, (c) two early polychromatic normoblasts, (d) two late polychromatic normoblasts and (e) two more mature late polychromatic normoblasts. The condensed chromatin in the basophilic normoblast is slightly coarser than in the proerythroblast. The nuclei of the late polychromatic normoblasts contain large masses of condensed chromatin.
Figure 1.6 Reticulocytes in peripheral blood stained supravitally with brilliant cresyl blue. Note the reticulum of precipitated ribosomes.
Figure 1.7 A small lymphocyte in a normal blood smear.
Figure 1.8 A large lymphocyte with several azurophilic cytoplasmic granules. Large granular lymphocytes include cytotoxic T cells and natural killer (NK) cells.
Chapter 2: Anaemia: General principles
Figure 2.1 Normal and abnormal red cells. (a) Normochromic, normocytic cells. The red cell should normally be approximately the same size as the nucleus of a small lymphocyte, and the cell should have an area of central pallor of approximately one-third its diameter. (b) Hypochromic, microcytic cells – a small lymphocyte is shown for comparison. (c) Oval macrocytes, typical of B12 deficiency. (d) Target cells and spherocytes in a blood film from a splenectomized patient. (e) Target cells from a patient with obstructive jaundice. (f) Howell–Jolly bodies within red cells, found typically in patients post splenectomy. Figure (a)–(c) are at similar magnification; (d)–(f) are at a lower magnification.
Figure 2.2 A summary of iron handling. Note that there is no physiological mechanism to enhance iron loss after it is absorbed from the duodenal enterocytes. Hepcidin, produced by the liver when iron replete, influences the production and/or function of key molecules in iron absorption, including ferroportin, divalent metal transporter 1 (DMT1) and transferrin.
Figure 2.3 Peripheral blood film from a patient with untreated iron deficiency anaemia. Hypochromic microcytes and elongated (‘pencil-shaped’) poikilocytes are present.
Figure 2.4 The distribution of the serum ferritin concentration in 105 women with stainable iron in the bone marrow () and in 69 women with no stainable iron ().
Figure 2.5 Marrow fragment containing normal quantities of storage iron. The haemosiderin stains blue (Perls' acid ferrocyanide stain).
Figure 2.6 Marrow fragment from a patient with iron deficiency anaemia showing an absence of storage iron (Perls' acid ferrocyanide stain). Contrast with Figure 2.5.
Figure 2.7 Marrow smear from a patient with primary acquired sideroblastic anaemia, stained by the Perls' acid ferrocyanide method (Prussian blue reaction). The erythroblasts contain several coarse blue–black iron-containing granules, arranged around the nucleus.
Figure 2.8 Electron micrograph of part of a ring sideroblast showing very electron-dense material between the cristae of enlarged mitochondria.
Figure 2.9 Biochemical pathways affected in vitamin B12 and folate deficiency. dTMP, deoxythymidine monophosphate; dTTP, deoxythymidine triphosphate; dUMP, deoxyuridine monophosphate; dUTP, deoxyuridine triphosphate; THF, tetrahydrofolate. Enzymes: 1, thymidylate synthase; 2, homocysteine methyltransferase (methionine synthase); 3, dihydrofolate reductase.
Figure 2.10 Glossitis in a woman with severe pernicious anaemia.
Figure 2.11 Blood film from a patient with pernicious anaemia showing oval macrocytes, other poikilocytes and a hypersegmented neutrophil.
Figure 2.12 (a) Early polychromatic normoblast from the marrow of a healthy subject. (b) Early polychromatic megaloblasts from a patient with severe pernicious anaemia. These cells are larger and have a more delicate, sieve-like nucleus containing smaller particles of condensed chromatin than the early polychromatic normoblast.
Figure 2.13 Two giant metamyelocytes near a normal-sized metamyelocyte in a marrow smear from a patient with untreated pernicious anaemia. There is also a megaloblast containing Howell–Jolly bodies (i.e. micronuclei).
Figure 2.14 Electron micrograph of a bone marrow macrophage from a patient with severe pernicious anaemia. The cytoplasm of the macrophage contains two ingested megaloblasts (arrowed) at various stages of degradation.
Chapter 3: Haemolytic anaemias
Figure 3.1 (a) A normocellular marrow fragment: about half its volume consists of haematopoietic cells (staining blue) and the remainder of unstained rounded fat cells. (b) A markedly hypercellular marrow fragment, as might be seen in the response to haemolysis; virtually all the fat cells are replaced by haematopoietic cells.
Figure 3.2 A classification of haemolytic anaemia by aetiology. G6PD, glucose-6-phosphate dehydrogenase; MAHA, microangiopathic haemolytic anaemia.
Figure 3.3 Schematic diagram of the red cell membrane cytoskeleton.
Figure 3.4 A blood film from a patient with hereditary spherocytosis showing many spherocytes. These are the smaller, more densely staining cells which lack the usual area of central pallor.
Figure 3.5 A blood film from a patient with hereditary elliptocytosis showing a high proportion of elliptical red cells.
Figure 3.6 A schematic diagram of the pathway of glucose metabolism in the red cell, to show the important role of G6PD. A decreased activity of the enzyme leads to a deficiency of the reducing compounds NADPH and glutathione (GSH).
Figure 3.7 Membrane-bound Heinz bodies consisting of denatured haemoglobin (supravital staining with methyl violet).
Figure 3.8 ‘Bite’ cells in the blood film of a patient with G6PD deficiency who had received primaquine. These red cells are irregular in shape, abnormally dense and show a poorly staining area just beneath part of the cell membrane (MGG stain).
Figure 3.9 Blood film from a patient with idiopathic autoimmune haemolytic anaemia (AIHA) (warm-reactive antibody) showing prominent spherocytosis and polychromasia. A nucleated red blood cell is also visible on the left of the image.
Figure 3.10 Numerous red cell agglutinates on a blood film from a patient with idiopathic cold haemagglutinin disease (CHAD).
Figure 3.11 Fragmented red cells (schistocytes) in the blood film of a patient with a malfunctioning aortic valve prosthesis.
Figure 3.12 Blood film from a patient with Plasmodium falciparum malaria showing several parasitized red cells. Red cells heavily parasitized with malaria may be subject to intravascular lysis.
Figure 3.13 Blood film from a patient with Plasmodium vivax malaria showing two parasitized red cells, each containing a single parasite (ring form or early trophozoite and an amoeboid late trophozoite). Another red cell contains a schizont. Some of the parasitized cells are slightly enlarged.
Chapter 4: Disorders of globin synthesis
Figure 4.1 Oxygen–haemoglobin dissociation curves.
Figure 4.2 Areas of high prevalence for the major Hb variants (C, E, S, D) and thalassaemia.
Figure 4.3 Blood film from a patient with HbH disease showing microcytosis, hypochromia, anisocytosis and poikilocytosis.
Figure 4.4 HbH inclusions seen on supravital staining with brilliant cresyl blue.
Figure 4.5 Electrophoresis of haemolysates on cellulose acetate (pH 8.5). The arrow marks the site of application of the haemolysate. (1) Normal adult. (2) Individual with sickle-cell trait; 35% of the Hb consists of HbS and most of the remainder is HbA. (3) Patient with sickle cell anaemia; most of the Hb is S and there is no A. (4) Compound heterozygote for HbS and HbC. This results in a sickling disorder that is often milder than that in homozygotes for HbS.
Figure 4.6 (a) High-performance liquid chromatography (HPLC) showing a trace with no variant haemoglobins but an increased peak at the retention time of HbA2, consistent with β-thalassaemia trait; and (b) HPLC trace showing a variant haemoglobin with the retention time of HbS.
Figure 4.7 Electron micrograph of a sickled red cell from a homozygote for HbS showing fibres of polymerized deoxygenated HbS running along the long axis of the cell.
Figure 4.8 Two sickle-shaped red cells and some partially sickled red cells from the blood film of a patient with sickle cell anaemia (homozygote for HbS).
Figure 4.9 An X-ray of the feet of a child with sickle cell anaemia 2 weeks after the onset of hand–foot syndrome, showing necrosis of the right fourth metatarsal.
Figure 4.10 A chronic leg ulcer with increased pigmentation of the surrounding skin in a woman with sickle cell anaemia.
Figure 4.11 Target cells and irregularly contracted cells in the blood film of a homozygote for HbC.
Chapter 5: Conditions associated with white cell abnormalities
Figure 5.1 Planned progressive therapy for febrile patients with neutropenia (<0.5 × 109 L). Note that exact antibiotic regimens will vary from hospital to hospital based on local policy.
Figure 5.2 Toxic granulation in two neutrophils from a patient with an infection.
Figure 5.3 Round, pale blue Döhle body near the nucleus of a neutrophil from a patient with extensive burns. Döhle bodies can also be oval or rod-shaped, and are more frequently seen at the periphery than at the centre of the cell.
Figure 5.4 (a) Schematic diagram to illustrate general principles of flow cytometry. (b) Schematic diagram showing how cells are presented to a laser light beam by hydrodynamic focusing.
Figure 5.5 Flow cytometry of normal bone marrow after incubating normal bone marrow cells with PerCP-labelled anti-CD45 antibody.
Figure 5.6 Two atypical mononuclear cells (reactive lymphocytes) and a neutrophil from a patient with glandular fever. Although the atypical mononuclear cells are similar in size to the monocyte in Figure 1.3, their cytoplasm is much more basophilic and not vacuolated.
Figure 5.7 Features of Epstein–Barr virus (EBV) infection and the resulting immune response. IgM antibody to viral capsid antigen (VCA) is diagnostic of a recent or continuing infection. EBNA, Epstein–Barr nuclear antigen; MA, membrane antigen.
Chapter 6: Structure and function of lymphoid tissue
Figure 6.1 The derivation of B cells, T cells and NK cells from stem cells.
Figure 6.2 (a) Histological section through a lymph node and (b) illustration of a stylized lymph node.
Figure 6.3 Schematic model of an IgG molecule.
Figure 6.4 A diagram illustrating gene rearrangement enabling antigen-binding diversity. During differentiation, a single B cell can synthesize heavy chains with different constant regions coupled to the same variable region. Note that it is the genetic locus itself that undergoes rearrangement, not merely the transcripts it generates. The T-cell receptor (TCR) undergoes gene rearrangement in a very similar way in T cells. C, constant region gene; D, diversity gene; JH, joining sequence; VH , variable gene.
Figure 6.5 Lymphomas arise from normal cellular components of the immune system. Pre-germinal centre cells may give rise to chronic lymphocytic leukaemia (CLL) or mantle cell lymphoma. The majority of other lymphomas arise from mutations in cells derived from the germinal centre or the post-germinal centre. MALT: mucosa associated lymphoid tissue.
Chapter 7: Lymphomas: General principles
Figure 7.1 Two Reed–Sternberg cells: their presence defines Hodgkin lymphoma.
Figure 7.2 Up-regulation of c-MYC in Burkitt lymphoma. A translocation between chromosome 14 and chromosome 8 juxtaposes the c-MYC oncogene with the immunoglobulin heavy chain gene enhancer, thereby up-regulating the oncogene c-MYC and driving the cell into cycle. The translocation of an oncogene to the vicinity of the Ig gene regulatory elements is a common feature in B-cell lymphomas.
Figure 7.3 cDNA microarray containing 10 000 spots showing differential gene expression. Red, high gene expression; green, low gene expression.
Figure 7.4 Schematic diagram to illustrate the molecular difference between low- and high-grade lymphomas.
Figure 7.5 Schematic diagram showing outcome for low- and high-grade lymphomas.
Figure 7.6 Typical immunophenotype of follicular lymphoma (paraffin section): (a) haematoxylin and eosin (H&E), (b) CD20, (c) bcl-2, (d) CD3, (e) Ki67 and (f) CD10.
Figure 7.7 CT image of a patient with lymphoma: (a) right axillary, anterior mediastinal nodal disease and bilateral pleural effusions; and (b) bulky retroperitoneal lymphadenopathy (intravenous and bowel contrast help define the lymphomatous masses).
Figure 7.8 The overall survival of patients with follicular lymphoma subdivided by the IPI score; p <0.001 for differences between the curves.
Figure 7.9 A schematic representation of key steps in B-cell signalling. Binding of the B-cell receptor by antigen induces a conformational change which exposes the immunoreceptor tyrosine-based activation motifs (ITAMs) on the associated CD79a/b complex. This means that these can be phosphorylated by the Src family kinases, Lyn, Fyn and Blk (Panel 1). This in turn creates a site to which the tyrosine kinase SYK can bind, with its resultant activation. SYK then goes to on phosphorylate phospholipase C γ2 (PLCγ2) and Bruton's tyrosine kinase (BTK), as well as B-cell linker (BLNK) and B-cell adaptor for phosphoinositide 3-kinase (BCAP) (Panel 2). These agents contribute to activation of the phosphoinositide-3 kinase (PI3K) (Panel 3). The PI3K pathway and BTK, along with additional signalling cascades, cause NK-κB activation, and activation of the MEK-ERK signalling cascades (Panel 4). The downstream effect is modulation of gene expression by transcription factors including NF-κB itself and MYC. Key stages in this process may be inhibited therapeutically (signified by the red asterisks). The BTK inhibitor ibrutinib and PI3K inhibitor idelalisib are in current clinical use, and inhibitors of many other components of this network are being evaluated for their possible therapeutic potential.
Figure 7.10 (a) The diagram shows the changes that occur during the maturation of a stem cell into plasma cells, and the stages of normal development at which key malignancies arise. Note that immature B cells and plasma cells do not express CD20. CLL, chronic lymphocytic leukaemia; HCR, heavy chain rearrangement; μ, mu heavy chain synthesis; κR/D, κ chain rearrangement or deletion; λR/D, λ chain rearrangement or deletion; sIgM, sIgG, sIgA, surface immunoglobulins M, G and A, respectively. (b) A schematic diagram of rituximab, a chimeric monoclonal antibody designed to bind to CD20 antigen on B cells inducing apoptosis and cell death.
Chapter 8: Classification of lymphoma
Figure 8.1 Pie chart showing the relative incidence of different non-Hodgkin lymphomas. For abbreviations see Tables 8.2 and 8.3.
Figure 8.2 Survival curves for patients with different types of lymphoma. (a,b) Good prognosis lymphomas. MALT, mucosa-associated lymphoid tissue, now also termed extranodal marginal zone lymphoma. (c,d) Poor prognosis lymphomas. Note that mantle cell lymphoma has the worst prognosis of any lymphoma.
Chapter 9: Neoplastic disorders of lymphoid cells
Figure 9.1 Photomicrograph showing Reed–Sternberg cells from a case of Hodgkin lymphoma.
Figure 9.2 Massive cervical lymphadenopathy in a young boy with Hodgkin lymphoma.
Figure 9.3 Actuarial risk of death from Hodgkin lymphoma (B) or other causes (A) in patients treated for Hodgkin lymphoma.
Figure 9.4 Bone marrow smear from a case of acute lymphoblastic leukaemia (ALL). The blasts are small or medium sized and have scanty cytoplasm. The nuclei have fine but densely packed, homogeneous-appearing chromatin and the nucleoli are small.
Figure 9.5 Blood film in a patient with chronic lymphocytic leukaemia (CLL). Note the presence of increased numbers of small lymphocytes and some smear cells.
Figure 9.6 (a) The non-specific histological appearance seen in the biopsy of a patient with mantle cell lymphoma; (b) staining using an antibody against cyclin D1, which is overexpressed in mantle cell lymphoma; (c) minimal disease after treatment identified by cyclin D1 staining; and (d) high-power view.
Figure 9.7 (a) Photomicrograph showing hairy cells in peripheral blood; (b) low power view of trephine biopsy showing infiltration and haemorrhage; and (c) high power view of trephine biopsy. The hairy cells have bean-shaped nuclei and abundant clear cytoplasm (appearing like a halo around the nucleus).
Figure 9.8 The survival of patients with diffuse large B-cell lymphoma (DLBCL) following treatment with CHOP alone, compared with CHOP plus rituximab (R-CHOP). Note that the survival difference is more pronounced for patients with low-risk disease.
Chapter 10: Plasma cell myeloma and other paraproteinaemias
Figure 10.1 A marrow smear from a patient with multiple myeloma (May-Grünwald–Giemsa (MGG) stain).
Figure 10.2 MRI of the spine showing spinal cord compression secondary to myeloma.
Figure 10.3 Fundi of the eyes in the hyperviscosity syndrome showing (a) retinal haemorrhages and (b) papilloedema.
Figure 10.4 Blood film from a patient with plasma cell myeloma showing marked red cell rouleau formation (MGG stain).
Figure 10.5 (a) Marrow smear showing myeloma cells reacting with antibody against λ chains; the reaction was demonstrated using an immunoalkaline phosphatase method. The cells did not react with antibody against κ chains and were therefore monoclonal in origin. The serum contained an IgD λ paraprotein. (b) Radiograph of the skull of a patient with multiple myeloma showing multiple discrete osteolytic lesions with no sclerosis at the margin.
Figure 10.6 Illustration of serum electrophoresis demonstrating a monoclonal band and reduced normal immunoglobulins. Source: Courtesy of Professor Hoffbrand.
Chapter 11: Neoplastic disorders of myeloid cells
Figure 11.1 Acute myeloid leukaemia (AML) (FAB category M1). The three leukaemic myeloblasts are considerably larger than adjacent red cells, have finely stippled nuclear chromatin and show prominent nucleoli (May-Grünwald–Giemsa (MGG) stain).
Figure 11.2 Myeloblasts of AML showing several Auer rods (MGG stain). These are azurophilic rod-shaped cytoplasmic inclusions that are exclusively found in some of the leukaemic myeloblasts of a small proportion of patients with AML, or chronic myeloid leukaemia (CML) in blast-cell transformation.
Figure 11.3 Flow cytometry demonstrating myeloid antigen expression in a case of AML. The blasts are CD117+ and CD13+.
Figure 11.4 (a) Hypogranular neutrophil from a patient with myelodysplastic syndrome (MDS). Note the lack of granules in the cytoplasm. (b) Neutrophil granulocyte from a heterozygote for the inherited Pelger–Huët anomaly. The nucleus is bilobed (spectacle-like) and has markedly condensed chromatin. In heterozygotes for this asymptomatic condition, 50–70% of neutrophils show these changes. Similar abnormalities may be found in some neutrophils, as an acquired condition in MDS.
Figure 11.5 Blood film from a patient with CML showing an increased number of white cells, mainly neutrophils, band cells and metamyelocytes. Note the presence of some myelocytes and basophils.
Figure 11.6 (a) Illustration of the translocation between chromosomes 22 and 9 leading to the formation of a novel oncogene BCR-ABL. Note that a variation of the same translocation occurs in some patients with ALL. The novel oncogene produces a tyrosine kinase, leading to cell proliferation. (b) Diagram showing the mechanism of action of imatinib. This drug inhibits the phosphorylation by BCR–ABL of tyrosine in protein (shown in green) and thereby interferes with its leukaemogenic effects.
Figure 11.7 Blood film of a patient with idiopathic myelofibrosis showing several teardrop-shaped poikilocytes and an abnormally large platelet (MGG stain).
Figure 11.8 (a) Trephine biopsy of the bone marrow of a patient with idiopathic myelofibrosis showing fibroblasts and collagen fibrosis (haematoxylin and eosin). (b) Section of the same trephine biopsy showing increased reticulin fibres (silver impregnation of reticulin).
Chapter 12: Bone marrow transplantation
Figure 12.1 The graph shows the number and percentage of allogeneic and autologous stem cell transplants reported in Europe in 2013. The majority of allogeneic stem cell transplants are performed for acute myeloid leukaemia (AML), while the majority of autologous transplants are performed for lymphoma (non-Hodgkin lymphoma (NHL) and Hodgkin disease (HD)) and plasma cell disorders (PCD). Other abbreviations: ALL, acute lymphoblastic leukaemia; BMF, bone marrow failure syndromes; CLL, chronic lymphocytic leukaemia; CML, chronic myeloid leukaemia; IDM, inherited disorders of metabolism; MDS, myelodysplastic syndromes; MPN, myeloproliferative neoplasms; PID, primary immunodeficiency.
Figure 12.2 Causes of death after transplants carried out in 2012–2013. GVHD, graft-versus-host disease. Source : D'Souza A, Zhu X. Current Uses and Outcomes of Hematopoietic Cell Transplantation (HCT): CIBMTR Summary Slides, 2016. Available at: http://www.cibmtr.org
Figure 12.3 Diagram showing the collection of peripheral blood stem cells (PBSC) using a COBE spectra apheresis machine. MNC, mononuclear cell; RBC, red blood cell.
Figure 12.4 The probability of survival after autologous transplants for Hodgkin lymphoma. CR, complete remission.
Chapter 13: Aplastic anaemia and pure red cell aplasia
Figure 13.1 Markedly hypocellular marrow fragment from a case of aplastic anaemia. There are only a few residual haematopoietic cells, most of the fragments consisting of fat cells.
Figure 13.2 Section of a trephine biopsy of the bone marrow from a patient with aplastic anaemia showing marked hypocellularity (haemotoxylin and eosin).
Chapter 14: Haemostasis, abnormal bleeding and anticoagulant therapy
Figure 14.1 Multiple pin-point haemorrhages (petechiae) on the legs of a patient with idiopathic thrombocytopenic purpura (ITP).
Figure 14.2 Large ecchymoses on both the upper arms of a woman with ITP.
Figure 14.3 Vascular malformations (reddish purple) on the lips of a patient with hereditary haemorrhagic telangiectasia; such lesions are found throughout the body and increase in number with advancing age. This rare condition is inherited as an autosomal dominant characteristic and may lead to recurrent gastrointestinal haemorrhage and chronic iron deficiency anaemia.
Figure 14.4 Pathways involved in fibrin generation after the activation of coagulation in vivo by tissue factor (TF). The suffix ‘a’ denotes the active form of each coagulation factor. Green arrows denote actions of thrombin; red arrows denote actions of other active enzymes and black arrows denote inhibition.
Figure 14.8 The natural anticoagulants. APC, activated protein C; AT, antithrombin; PC, protein C; PS, protein S.
Figure 14.5 The sequence of coagulation in vitro brought about by by either contact activation of factor XII or by addition of tissue factor. The suffix ‘a’ denotes the active form of each coagulation factor. The former is the basis of the activated partial thromboplastin time (APTT) and the latter the prothrombin time (PT). HMWK, high molecular weight kininogen; PK, pre-kallikrein.
Figure 14.6 The fibrinolytic mechanism. PAI, plasminogen activator inhibitor; SK:Plgn, streptokinase–plasminogen complex; tPA, tissue plasminogen activator; uPA, urokinase plasminogen activator.
Figure 14.7 Haemarthrosis of the shoulder joint in a patient with haemophilia A.
Chapter 15: Blood groups and blood transfusion
Figure 15.1 Hazards of transfusion in the UK, 1997–2014, as reported to the SHOT Committee (n = 14 822).
Chapter 16: Cellular and molecular investigations in haematology
Figure 16.1 G-banded metaphase spread showing deletion of 5q. Thin arrow, normal chromosome 5; thick arrow, del(5q).
Figure 16.2 BCR/ABL1 FISH showing standard rearrangement consistent with t(9;22). Both cells shown have a single Philadelphia chromosome: the normal BCR and ABL signals are shown as the separate red and green signals; the two fused signals (arrowed in the lower cell) represent the derivative chromosomes each bearing part of the BCR gene and part of ABL1.
Figure 16.3 Schematic representation of the polymerase chain reaction (PCR). Here a single copy of double-stranded DNA is used as the starting template. Following two cycles of PCR, four copies are generated; an ongoing exponential increase is achieved with further cycles, and many millions of target copies will be generated by a standard PCR.
Figure 16.4 Two Gene-Scan plots showing the results of clonality assessment at the TCRG locus (a) and TCRB locus (b). In each panel, the top trace shows a polyclonal control with a range of PCR product sizes; the lower two traces in each panel are consistent with a monoclonal pattern of TCR rearrangement. Performed using BIOMED2 primers. The y-axis denotes the amount of PCR product; the x-axis show the size of the PCR product.
Figure 16.5 Relative quantitation of abnormal transcript levels by quantitative PCR (qPCR). The top panel shows a qPCR trace in which five dilutions of a known concentration control transcript (turquoise to dark blue) have been run alongside a patient sample (green). The amount of transcript relative to the standard can then be read from a standard curve (lower panel).
Figure 16.6 A schematic representation of Sanger sequencing.
Figure 16.7 An overview of next-generation sequencing. See text for details.
List of Tables
Chapter 1: An introduction to haematopoiesis
Table 1.1 The sequence of events during B-cell differentiation
Table 1.2 The sequence of events during T-cell differentiation
Table 1.3 The main functions of blood cells
Chapter 2: Anaemia: General principles
Table 2.1 Reference ranges for haemoglobin (Hb) values
Table 2.2 Morphological classification of anaemia
Table 2.3 Measurements of iron status in people with normal iron stores, individuals with iron depletion without anaemia, and in iron deficiency anaemia
Table 2.4 Key features of vitamin B12 and folate nutrition and absorption
Chapter 3: Haemolytic anaemias
Table 3.1 Laboratory findings indicative of haemoysis
Chapter 4: Disorders of globin synthesis
Table 4.1 Different clinical and haematological abnormalities associated with some structural haemoglobin variants
Table 4.2 Clinical manifestations of sickle-cell anaemia
Chapter 5: Conditions associated with white cell abnormalities
Table 5.1 Some inherited abnormalities of neutrophil morphology and/or function
Chapter 7: Lymphomas: General principles
Table 7.1 Examples of high- and low-grade lymphoid neoplasms
Table 7.2 Staging of lymphomas
Table 7.3 The international prognostic index: features conferring a worse prognosis in patients with diffuse large B-cell lymphoma
Chapter 8: Classification of lymphoma
Table 8.1 Hodgkin lymphomas
Table 8.2 Non-Hodgkin B-cell lymphomas
Table 8.3 Non-Hodgkin T-cell lymphomas
Chapter 9: Neoplastic disorders of lymphoid cells
Table 9.1 World Health Organization (WHO) classification of the histological appearances of lymph nodes in classical Hodgkin lymphoma
Table 9.2 Basic features of the Ann Arbor staging system
Chapter 10: Plasma cell myeloma and other paraproteinaemias
Table 10.1 The differences between myeloma and monoclonal gammopathy of undetermined significance (MGUS)
Chapter 11: Neoplastic disorders of myeloid cells
Table 11.1 World Health Organization (WHO) classification of acute myeloid leukaemia (AML)
Table 11.2 Cytogenetic abnormalities that have been found to be associated with better prognosis in AML
Chapter 12: Bone marrow transplantation
Table 12.1 Diseases for which allogeneic and autologous bone marrow transplantation (BMT) may be considered
Chapter 15: Blood groups and blood transfusion
Table 15.1 Appropriate blood groups for transfusion
Table 15.2 The relationship between the number of fetal red cells in the maternal circulation after labour and the subsequent immunization of the mother
Chapter 16: Cellular and molecular investigations in haematology
Table 16.1 Selected chromosomal translocations associated with haematological disease
Table 16.2 Selected genes frequently mutated in haematological disease
Lecture Notes
Christian Hatton
MA, FRCP, FRCPath
Deborah Hay
DPhil, MRCP, FRCPath
David M. Keeling
MD, FRCP, FRCPath
Tenth Edition
This tenth edition first published 2018 © 2018 by John Wiley & Sons
Edition History
John Wiley & Sons Ltd (9e, 2013)
All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by law. Advice on how to obtain permission to reuse material from this title is available at http://www.wiley.com/go/permissions.
The right of Christian Hatton, Deborah Hay and David M. Keeling to be identified as the authors in this work has been asserted in accordance with law.
Registered Office(s)
John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, USA
John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, UK
Editorial Office
The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, UK
For details of our global editorial offices, customer services, and more information about Wiley products visit us at www.wiley.com.
Wiley also publishes its books in a variety of electronic formats and by print-on-demand. Some content that appears in standard print versions of this book may not be available in other formats.
Limit of Liability/Disclaimer of Warranty
The contents of this work are intended to further general scientific research, understanding, and discussion only and are not intended and should not be relied upon as recommending or promoting scientific method, diagnosis, or treatment by physicians for any particular patient. In view of ongoing research, equipment modifications, changes in governmental regulations, and the constant flow of information relating to the use of medicines, equipment, and devices, the reader is urged to review and evaluate the information provided in the package insert or instructions for each medicine, equipment, or device for, among other things, any changes in the instructions or indication of usage and for added warnings and precautions. While the publisher and authors have used their best efforts in preparing this work, they make no representations or warranties with respect to the accuracy or completeness of the contents of this work and specifically disclaim all warranties, including without limitation any implied warranties of merchantability or fitness for a particular purpose. No warranty may be created or extended by sales representatives, written sales materials or promotional statements for this work. The fact that an organization, website, or product is referred to in this work as a citation and/or potential source of further information does not mean that the publisher and authors endorse the information or services the organization, website, or product may provide or recommendations it may make. This work is sold with the understanding that the publisher is not engaged in rendering professional services. The advice and strategies contained herein may not be suitable for your situation. You should consult with a specialist where appropriate. Further, readers should be aware that websites listed in this work may have changed or disappeared between when this work was written and when it is read. Neither the publisher nor authors shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages.
Library of Congress Cataloging-in-Publication Data
Names: Hatton, Christian (Hematologist), author. | Hay, Deborah, 1977- author. | Keeling, David M. (David Michael), author.
Title: Lecture notes. Haematology / Christian Hatton, Deborah Hay, David M. Keeling.
Other titles: Haematology
Description: Tenth edition. | Hoboken, NJ : Wiley, 2017. | Preceded by Lecture notes. Haematology / Christian Hatton ... [et al.]. 9th ed. Chichester, West Sussex : John Wiley & Sons, 2013. | Includes bibliographical references and index. |
Identifiers: LCCN 2017013692 (print) | LCCN 2017014923 (ebook) | ISBN 9781119264262 (pdf) | ISBN 9781119264279 (epub) | ISBN 9781119264255 (paperback)
Subjects: | MESH: Hematologic Diseases | Blood Physiological Phenomena
Classification: LCC RC636 (ebook) | LCC RC636 (print) | NLM WH 120 | DDC 616.1/5-dc23
LC record available at https://lccn.loc.gov/2017013692
Cover Design: Wiley
Cover Image: \copyright KTSDESIGN/SCIENCE PHOTO LIBRARY/Gettyimages
Modern haematologyHaematology Lecture Notes , with a new chapter outlining the molecular and cellular techniques that are central to haematology. Our online companion website also features self-assessment questions which allow the reader to apply his or her knowledge to clinical cases.
As always, we are grateful to our colleagues for their help and advice in the production of this book. We are especially grateful to Professor Kevin Gatter of the Nuffield Division of Clinical Laboratory Sciences for kindly allowing us to use his excellent histological images, and to Drs Angela Hamblin, Robert Danby, Jaimal Kothari and Adam Mead, consultant haematologists, for their advice and suggestions. We are also grateful to those readers who have provided feedback on previous editions.
We hope that students and junior doctors continue to find Haematology Lecture Notes a useful introduction to this rapidly changing specialty.
About the companion website
This book is
www.wiley.com/go/hatton/haematology/10e
The website includes:
Interactive multiple choice questions for each chapter
Chapter overviews
Further reading
