Essential haematology.

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Hoffbrand’s Essential Haematology Contents Preface to the Seventh Edition Preface to the First Edition How to use your textbook About the companion website 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