| Preface |
|
vii | |
| About the companion website |
|
ix | |
| 1 An introduction to haematopoiesis |
|
1 | (10) |
|
|
|
1 | (1) |
|
|
|
1 | (1) |
|
Haematopoietic stem cells |
|
|
1 | (2) |
|
Differentiating blood cells |
|
|
3 | (1) |
|
|
|
3 | (4) |
|
Granulocytes and their function |
|
|
3 | (2) |
|
Monocytopoiesis and monocyte function |
|
|
5 | (1) |
|
Megakaryocytes and platelet function |
|
|
5 | (2) |
|
Erythropoiesis and red cell function |
|
|
7 | (1) |
|
|
|
7 | (2) |
|
|
|
9 | (2) |
| 2 Anaemia: General principles |
|
11 | (16) |
|
|
|
11 | (1) |
|
|
|
11 | (1) |
|
Symptoms and signs of anaemia |
|
|
12 | (1) |
|
Normal control of red cell production |
|
|
12 | (1) |
|
Morphological classification of anaemias |
|
|
13 | (1) |
|
Microcyti anaemia: iron handling and iron deficiency anaemia |
|
|
13 | (7) |
|
|
|
14 | (2) |
|
How does iron deficiency arise? |
|
|
16 | (1) |
|
Manifestations of iron deficiency |
|
|
17 | (1) |
|
Confirming a diagnosis of iron deficiency |
|
|
18 | (1) |
|
|
|
19 | (1) |
|
Other causes of microcytic hypochromic anaemia |
|
|
19 | (1) |
|
|
|
20 | (1) |
|
Anaemia of chronic disease |
|
|
20 | (1) |
|
Other causes of normocytic anaemia |
|
|
21 | (1) |
|
|
|
21 | (5) |
|
Causes of megaloblastic anaemia: vitamin B12 and folate deficiency |
|
|
21 | (1) |
|
How do B12 and folate deficiency arise? |
|
|
21 | (2) |
|
Clinical manifestations of B12 and folate deficiency |
|
|
23 | (1) |
|
Confirming a diagnosis of B12 or folate deficiency |
|
|
24 | (1) |
|
|
|
25 | (1) |
|
Other causes of megaloblastosis |
|
|
25 | (1) |
|
Normoblastic macrocytosis |
|
|
25 | (1) |
|
Polycythaemia (erthrocytosis) |
|
|
26 | (1) |
|
|
|
26 | (1) |
| 3 Haemolytic anaemias |
|
27 | (14) |
|
|
|
27 | (1) |
|
Laboratory evidence of haemolysis |
|
|
28 | (1) |
|
Clinical features of haemolysis |
|
|
29 | (1) |
|
Classifying haemolytic anaemias and establishing a diagnosis |
|
|
30 | (1) |
|
Congenital haemolytic anaemias |
|
|
30 | (6) |
|
Haemolysis resulting from defects of the red cell membrane |
|
|
30 | (1) |
|
Hereditary sphyerocytosis |
|
|
30 | (2) |
|
|
|
32 | (1) |
|
Hereditary elliptocytosis and hereditary propoikilocytoisis |
|
|
33 | (1) |
|
Haemolysis caused by abnormalities of red cell enzymes |
|
|
33 | (1) |
|
Glucose-t-phosphate dehydrogenase deficiency |
|
|
33 | (3) |
|
Treatment of G6PD deficiency |
|
|
36 | (1) |
|
Other red cell enzyme deficiencies causing haemolysis |
|
|
36 | (1) |
|
Haemolysis resulting from haemoglobin defects |
|
|
36 | (1) |
|
Acquired haemolytic anaemias |
|
|
36 | (3) |
|
Immune haemolytic anaemias |
|
|
36 | (1) |
|
Autoimmune haemolytic anaemias |
|
|
37 | (1) |
|
|
|
37 | (1) |
|
Cold haemagglutinin disease |
|
|
38 | (1) |
|
Non-immune haemolytic anaemias |
|
|
39 | (2) |
|
Mechanical damage to red cells |
|
|
39 | (1) |
|
Non-immune haemolytic anaemia resulting from drugs |
|
|
40 | (1) |
|
|
|
40 | (1) |
| 4 Disorders of globin synthesis |
|
41 | (14) |
|
|
|
41 | (1) |
|
Normal structure and function of haemoglobin |
|
|
41 | (2) |
|
|
|
43 | (4) |
|
|
|
44 | (1) |
|
alpha+ Thalassaemia trait |
|
|
44 | (1) |
|
alpha0 Thalassaemia trait |
|
|
44 | (1) |
|
|
|
44 | (1) |
|
Hb Bart's hydrops fetalis syndrome |
|
|
44 | (1) |
|
|
|
45 | (1) |
|
|
|
45 | (1) |
|
Homozygous beta-thalassaemia |
|
|
45 | (1) |
|
Clinical classification of the thalasaemias |
|
|
46 | (1) |
|
Clinical course and complications of thalassaemia major |
|
|
46 | (1) |
|
Treatement of beta-thalassaemia major |
|
|
46 | (1) |
|
Genetic counselling and antenatal diagnosis of beta-thalassaemia major |
|
|
47 | (1) |
|
Structural haemoglobin variants |
|
|
47 | (6) |
|
|
|
47 | (1) |
|
|
|
48 | (1) |
|
|
|
49 | (1) |
|
|
|
50 | (2) |
|
|
|
52 | (1) |
|
|
|
53 | (2) |
| 5 Conditions associated with white cell abnormalities |
|
55 | (10) |
|
|
|
55 | (1) |
|
|
|
55 | (2) |
|
|
|
55 | (2) |
|
|
|
57 | (1) |
|
|
|
56 | (1) |
|
Abnormalities of granulocyte morphology and function |
|
|
57 | (1) |
|
|
|
57 | (1) |
|
|
|
58 | (1) |
|
|
|
58 | (1) |
|
Lymphocytosis and lymphopenia |
|
|
58 | (1) |
|
|
|
58 | (1) |
|
|
|
58 | (1) |
|
Immunophenotyping by flow cytometry |
|
|
59 | (2) |
|
|
|
61 | (2) |
|
|
|
61 | (2) |
|
|
|
61 | (2) |
|
|
|
61 | (1) |
|
|
|
61 | (2) |
|
|
|
63 | (1) |
|
|
|
63 | (1) |
|
|
|
63 | (1) |
|
Leucoerythroblastic reaction |
|
|
63 | (2) |
| 6 Structure and function of lymphoid tissue |
|
65 | (6) |
|
|
|
65 | (1) |
|
|
|
65 | (1) |
|
|
|
66 | (1) |
|
Immunoglobulin structure and gene rearrangement |
|
|
66 | (4) |
|
|
|
67 | (1) |
|
|
|
67 | (3) |
|
|
|
70 | (1) |
|
B-cell selection and maturation |
|
|
70 | (1) |
|
T-lymphocyte antigen receptors |
|
|
70 | (1) |
|
|
|
70 | (1) |
|
Cellular origin of lymphomas |
|
|
70 | (1) |
| 7 Lymphomas: General principles |
|
71 | (10) |
|
|
|
71 | (1) |
|
Lymphomas versus leukaemias |
|
|
71 | (1) |
|
|
|
71 | (10) |
|
Aetiology and epidemiology |
|
|
71 | (1) |
|
Cytogeneics and molecular considerations |
|
|
72 | (4) |
|
|
|
76 | (1) |
|
Nodal and extranodal lymphomas |
|
|
76 | (1) |
|
Diagnosis is made by biopsy |
|
|
76 | (1) |
|
|
|
76 | (1) |
|
|
|
76 | (1) |
|
|
|
77 | (1) |
|
|
|
77 | (4) |
| 8 Classification of lymphoma |
|
81 | (4) |
|
|
|
81 | (4) |
| 9 Neoplastic disorders of lymphoid cells |
|
85 | (12) |
|
|
|
85 | (1) |
|
|
|
85 | (3) |
|
|
|
86 | (1) |
|
|
|
87 | (1) |
|
|
|
87 | (1) |
|
|
|
87 | (1) |
|
Positron emission tomography scanning and risk-adapted therapy |
|
|
88 | (1) |
|
|
|
89 | (8) |
|
Acute lymphoblastic leukaemia |
|
|
89 | (1) |
|
|
|
89 | (1) |
|
|
|
89 | (1) |
|
Clinical and laboratory features |
|
|
89 | (1) |
|
|
|
89 | (1) |
|
|
|
90 | (1) |
|
|
|
90 | (1) |
|
Chronic lymphocytic leukaemia |
|
|
90 | (1) |
|
|
|
91 | (1) |
|
Small lymphocytic B-cell lymphoma |
|
|
91 | (1) |
|
|
|
92 | (1) |
|
Lymphoplasmacytic lymphoma/Waldenstrom's macroglobulinaemia |
|
|
92 | (1) |
|
|
|
92 | (1) |
|
|
|
92 | (1) |
|
|
|
93 | (1) |
|
|
|
93 | (2) |
|
Diffuse large B-cell lymphoma |
|
|
95 | (1) |
|
|
|
95 | (1) |
|
Extranodal marginal zone lymphomas, including the group previously known as MALT lymphomas |
|
|
96 | (1) |
|
|
|
96 | (1) |
|
Mycosis fungoides and Sezary syndrome |
|
|
96 | (1) |
| 10 Plasma cell myeloma and other paraproteinaemias |
|
97 | (8) |
|
|
|
97 | (1) |
|
|
|
97 | (5) |
|
|
|
97 | (1) |
|
|
|
98 | (1) |
|
|
|
98 | (1) |
|
|
|
98 | (1) |
|
|
|
98 | (1) |
|
|
|
99 | (1) |
|
|
|
99 | (1) |
|
|
|
99 | (1) |
|
|
|
99 | (2) |
|
|
|
101 | (1) |
|
|
|
101 | (1) |
|
|
|
101 | (1) |
|
|
|
101 | (1) |
|
|
|
101 | (1) |
|
Other paraprotein-aemias and related disorders |
|
|
102 | (3) |
|
Benign paraproteinaemia (benign monoclonal gammaopathy or MGUS) |
|
|
102 | (4) |
|
|
|
102 | (1) |
|
Waldenstrom's macroglobulinaemia |
|
|
103 | (1) |
|
|
|
103 | (1) |
|
Other lymphoproliferative disorders |
|
|
103 | (2) |
| 11 Neoplastic disorders of myeloid cells |
|
105 | (12) |
|
|
|
105 | (1) |
|
|
|
106 | (3) |
|
|
|
106 | (1) |
|
|
|
106 | (1) |
|
|
|
106 | (1) |
|
|
|
106 | (1) |
|
AML with recurrent genetic abnormalities |
|
|
107 | (1) |
|
Acute promyelocytic leukaemia (M3) |
|
|
108 | (1) |
|
|
|
109 | (1) |
|
|
|
109 | (1) |
|
|
|
109 | (1) |
|
Bone marrow transplantation |
|
|
109 | (1) |
|
The myelodysplastic syndromes |
|
|
109 | (2) |
|
|
|
110 | (1) |
|
|
|
110 | (1) |
|
Myeloproliferative disorders |
|
|
111 | (6) |
|
Chronic myeloid leukaemia |
|
|
111 | (1) |
|
|
|
111 | (1) |
|
|
|
111 | (1) |
|
|
|
111 | (2) |
|
|
|
112 | (1) |
|
|
|
113 | (1) |
|
|
|
113 | (1) |
|
Laboratory findings and natural history |
|
|
113 | (1) |
|
|
|
113 | (1) |
|
|
|
114 | (1) |
|
|
|
114 | (1) |
|
|
|
114 | (1) |
|
|
|
114 | (1) |
|
|
|
114 | (1) |
|
Essential Thrombocythaemia |
|
|
115 | (4) |
|
|
|
116 | (1) |
|
|
|
116 | (1) |
|
|
|
116 | (1) |
| 12 Bone marrow transplantation |
|
117 | (8) |
|
|
|
117 | (2) |
|
Allogeneic bone marrow transplantation |
|
|
119 | (1) |
|
Complications of allogeneic BMT |
|
|
120 | (5) |
|
|
|
120 | (1) |
|
Graft-versus-host disease |
|
|
120 | (1) |
|
|
|
120 | (1) |
|
|
|
120 | (1) |
|
Graft-versus-leukaemia/lymphoma effect |
|
|
120 | (1) |
|
Reduced intensity conditioning transplant |
|
|
121 | (1) |
|
Haploidentical bone marrow transplantation |
|
|
121 | (1) |
|
Autologous bone marrow transplantation (high-dose therapy) |
|
|
121 | (4) |
| 13 Aplastic anaemia and pure red cell aplasia |
|
125 | (6) |
|
|
|
125 | (1) |
|
|
|
125 | (4) |
|
Acquired aplastic anaemia |
|
|
125 | (1) |
|
|
|
125 | (1) |
|
|
|
126 | (1) |
|
|
|
126 | (1) |
|
|
|
126 | (1) |
|
|
|
127 | (1) |
|
|
|
127 | (1) |
|
|
|
127 | (2) |
|
|
|
129 | (2) |
| 14 Haemostasis, abnormal bleeding and anticoagulant therapy |
|
131 | (20) |
|
|
|
131 | (1) |
|
|
|
132 | (1) |
|
Classification of haemostatic defects |
|
|
132 | (1) |
|
|
|
132 | (2) |
|
|
|
132 | (1) |
|
|
|
133 | (1) |
|
Tests of platelet function |
|
|
134 | (1) |
|
|
|
134 | (1) |
|
Platelet function analyser |
|
|
134 | (1) |
|
Platelet aggregation studies |
|
|
134 | (1) |
|
Thrombocytopenic and non-thrombocytopenic purpura |
|
|
135 | |
|
Causes of thrombocytopenia |
|
|
134 | (3) |
|
Failure of platelet production |
|
|
135 | (1) |
|
Shortened platelet survival |
|
|
135 | (1) |
|
Immune thrombocytopenic purpura |
|
|
135 | (1) |
|
|
|
136 | (1) |
|
|
|
136 | (1) |
|
Secondary autoimmune thrombocytopenic purpura |
|
|
137 | (1) |
|
Drug-induced immune thrombocytopenia |
|
|
137 | (1) |
|
Other immune thrombocytopenias |
|
|
137 | (1) |
|
Thrombotic thrombocytopenic purpura |
|
|
137 | (1) |
|
Increased splenic pooling |
|
|
137 | (1) |
|
Abnormalities of platelet function |
|
|
137 | (1) |
|
|
|
137 | (1) |
|
|
|
138 | (2) |
|
|
|
138 | (1) |
|
|
|
138 | (1) |
|
|
|
138 | (1) |
|
|
|
138 | (1) |
|
Normal coagulation mechanism |
|
|
138 | (2) |
|
The fibrinolytic mechanism |
|
|
140 | (1) |
|
Tests for clotting defects |
|
|
140 | (1) |
|
Activated partial thromboplastin time |
|
|
141 | (1) |
|
Congenital coagulation disorders |
|
|
141 | (4) |
|
Haemophilia A (factor VIII deficiency) |
|
|
141 | (1) |
|
Genetics, prevalence and biochemistry |
|
|
142 | (1) |
|
Detection of carriers and antenatal diagnosis |
|
|
142 | (1) |
|
|
|
142 | (1) |
|
|
|
143 | (1) |
|
|
|
143 | (1) |
|
Haemophilia B (factor IX deficiency, Christmas disease) |
|
|
144 | (1) |
|
|
|
144 | (1) |
|
Deficiency of other clotting factors |
|
|
145 | (1) |
|
Acquired coagulation disorders |
|
|
145 | (1) |
|
Disseminated intravascular coagulation |
|
|
145 | (1) |
|
|
|
146 | (1) |
|
|
|
146 | (1) |
|
|
|
146 | (1) |
|
|
|
146 | (1) |
|
|
|
146 | (1) |
|
|
|
147 | (1) |
|
Direct oral anticoagulants (DOACs) |
|
|
|
Investigation of a patient with abnormal bleeding |
|
|
147 | (1) |
|
Natural anticoagulant mechanisms and the prothrombotic state (thrombophilia) |
|
|
148 | (3) |
|
|
|
148 | (1) |
|
|
|
148 | (1) |
|
Factor V Leiden and APC resistance |
|
|
148 | (1) |
|
Prothrombin allele G20210A |
|
|
149 | (1) |
|
Antiphospholipid syndrome |
|
|
149 | (2) |
| 15 Blood groups and blood transfusion |
|
151 | (12) |
|
|
|
151 | (1) |
|
Blood transfusion and blood components |
|
|
151 | (3) |
|
Transfusing red blood cells |
|
|
151 | (1) |
|
|
|
152 | (1) |
|
|
|
153 | (1) |
|
Other blood group systems |
|
|
153 | (1) |
|
Cross-matching and compatibility |
|
|
153 | (1) |
|
|
|
154 | (1) |
|
Procedure for obtaining compatible blood |
|
|
154 | (1) |
|
Haemolytic disease of the newborn |
|
|
154 | (2) |
|
|
|
155 | (1) |
|
Management of mother and child |
|
|
156 | (1) |
|
Other blood components: platelets, plasma and granulocytes |
|
|
156 | (1) |
|
Hazards of blood transfusion: The SHOT report |
|
|
157 | (4) |
|
Haemolytic reactions from incompatible red cells |
|
|
158 | (1) |
|
Transfusion-transmitted infections |
|
|
158 | (1) |
|
Variant Creutzfeldt-Jakob disease |
|
|
159 | (1) |
|
|
|
159 | (1) |
|
|
|
159 | (1) |
|
|
|
160 | (1) |
|
Transfusion-associated graft-versus host disease |
|
|
160 | (1) |
|
Immediate-type hypersensitivity |
|
|
160 | (1) |
|
Transfusion-related acute lung injury |
|
|
160 | (1) |
|
|
|
160 | (1) |
|
|
|
161 | (1) |
|
|
|
161 | (1) |
|
Management of transfusion reactions |
|
|
161 | (1) |
|
|
|
161 | (2) |
| 16 Cellular and molecular investigations in haematology |
|
163 | (10) |
|
|
|
163 | (1) |
|
|
|
163 | (1) |
|
Cytogenetics and fluorescence in situ hybridization |
|
|
163 | (2) |
|
|
|
165 | (6) |
|
Polymerase chain reaction |
|
|
166 | (1) |
|
|
|
167 | (1) |
|
Real time or semi-quantitative PCR |
|
|
168 | (1) |
|
Next-generation sequencing |
|
|
169 | (2) |
|
An integrated haematology laboratory report |
|
|
171 | (1) |
|
|
|
171 | (2) |
| Index |
|
173 | |
