Irene Roberts is Emeritus Professor of Paediatric Haematology at the Department of Paediatrics and MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford. She was formerly Professor of Paediatric Haematology at Imperial College London and Honorary Consultant Paediatric Haematologist at St Mary’s and Hammersmith Hospitals, Imperial College Healthcare NHS Trust where she established a neonatal haematology diagnostic service based on daily evaluation of peripheral blood films over several decades. Her research focuses on the molecular and biological characteristics of blood disorders in the fetus and early childhood particularly in Down syndrome. Barbara J. Bain is a Professor of Diagnostic Haematology at St Mary’s Hospital Campus, Imperial College Faculty of Medicine. She is also a Consultant Haematologist at St Mary’s Hospital, London, UK. Her research has been focused on morphology of blood cells, ethnic and biological differences in haematological variables and cytogenetics and molecular genetics in relation to haematological malignancy. She has collaborated with numerous experts in the field and contributed to the WHO Classification of Tumours of Haemopoietic and Lymphoid Tissues.

• Preface viiiAbbreviations x1 The full blood count and blood film in healthy term and preterm neonates 1Introduction 1Brief outline of the ontogeny of haemopoiesis 1Properties of fetal haemopoietic stem and progenitor cells 2Red blood cell production and development in the fetus and neonate 5Erythropoietin production in the fetus and neonate 6Haemoglobin synthesis and red blood cell production in the fetus and newborn 6Red blood cell lifespan and the red blood cell membrane in the fetus and neonate 9Red blood cell metabolism in the fetus and neonate 10Iron metabolism in the fetus and neonate 11Normal values for red blood cell parameters in the fetus and neonate 12Leucocytes in the fetus and newborn 17Leucocyte production and function in the fetus and neonate 18Platelets and megakaryocytes in the fetus and neonate 23Developmental megakaryopoiesis and thrombopoiesis 23Platelet numbers in the neonate and fetus – normal values 24Neonatal platelet function 25Practical problems in interpreting neonatal blood counts and films 25Sample quality/artefacts 25Site of sampling 26Gestational age and postnatal age 27Pregnancy-associated complications and mode of delivery 28References 282 Red cell disorders: Anaemia, jaundice, polycythaemia and cyanosis 38Neonatal anaemia 38Definition and clinical significance of neonatal anaemia 38Neonatal anaemia due to reduced red cell production 39Neonatal anaemia due to increased red cell destruction 47Neonatal anaemia due to haemoglobinopathies and other microcytic anaemias 67Neonatal anaemia due to blood loss 76Anaemia of prematurity 81A simple diagnostic approach to neonatal anaemia 83Neonatal polycythaemia 85Haematological causes of cyanosis 86Principles of red cell transfusion in neonates 86Illustrative cases 88Abbreviations used in the illustrative cases 110References 1103 Neonatal infection and leucocyte disorders 128Leucocyte abnormalities in neonatal systemic disease 128Increases in leucocyte numbers 128Neonatal infection and its differential diagnosis: clues from the blood count and blood film 135Storage disorders: diagnostic clues from the blood film 144Neonatal neutropenia 145Definition and causes of neutropenia 145Immune neutropenia 148Inherited congenital or neonatal neutropenia 150Haematological features of neonates with Down syndrome 154Congenital leukaemia 154Leukaemia and preleukaemia in neonates with Down syndrome 156Acute leukaemia in neonates without Down syndrome 160Juvenile myelomonocytic leukaemia and Noonan syndrome myeloproliferative disorder 168Illustrative cases 169Abbreviations used in the illustrative cases 176References 1764 Disorders of platelets and coagulation, thrombosis and blood transfusion 190Thrombocytopenia overview 190Causes of neonatal thrombocytopenia: a practical classification based on age at onset 192Fetal thrombocytopenia 194Early-onset neonatal thrombocytopenia (presenting at <72 hours of age) 194Late-onset neonatal thrombocytopenia (presenting at >72 hours of age) 196Conditions leading to clinically significant thrombocytopenia in the neonate 197Fetal/neonatal alloimmune thrombocytopenia 197Neonatal thrombocytopenia due to maternal autoimmune disease 200Thrombocytopenia due to congenital infections 201Neonatal thrombocytopenia associated with chromosomal abnormalities 205Inherited thrombocytopenia 206Investigation of neonatal thrombocytopenia 215Management of neonatal thrombocytopenia 215Indications for platelet transfusion 216Platelet function disorders 217Inherited platelet function disorders with normal platelet counts presenting in the neonate 218Thrombocytosis 218Abnormalities of coagulation 220Developmental haemostasis 220Laboratory investigation of coagulation disorders in the neonate 220Acquired coagulation abnormalities 221Inherited coagulation disorders 223Thrombosis 224Screening tests for thrombophilia in neonates 224Acquired thrombotic abnormalities 225Inherited thrombotic abnormalities 225General principles of neonatal platelet and plasma component transfusion 226Platelet transfusion 226Fresh frozen plasma 226Cryoprecipitate 227Prothrombin complex and recombinant factor VIIa 227Illustrative cases 227Abbreviations used in the illustrative cases 233References 234Index 254

Irene Roberts is Emeritus Professor of Paediatric Haematology at the Department of Paediatrics and MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford. She was formerly Professor of Paediatric Haematology at Imperial College London and Honorary Consultant Paediatric Haematologist at St Mary’s and Hammersmith Hospitals, Imperial College Healthcare NHS Trust where she established a neonatal haematology diagnostic service based on daily evaluation of peripheral blood films over several decades. Her research focuses on the molecular and biological characteristics of blood disorders in the fetus and early childhood particularly in Down syndrome. Barbara J. Bain is a Professor of Diagnostic Haematology at St Mary’s Hospital Campus, Imperial College Faculty of Medicine. She is also a Consultant Haematologist at St Mary’s Hospital, London, UK. Her research has been focused on morphology of blood cells, ethnic and biological differences in haematological variables and cytogenetics and molecular genetics in relation to haematological malignancy. She has collaborated with numerous experts in the field and contributed to the WHO Classification of Tumours of Haemopoietic and Lymphoid Tissues.

• Preface viiiAbbreviations x1 The full blood count and blood film in healthy term and preterm neonates 1Introduction 1Brief outline of the ontogeny of haemopoiesis 1Properties of fetal haemopoietic stem and progenitor cells 2Red blood cell production and development in the fetus and neonate 5Erythropoietin production in the fetus and neonate 6Haemoglobin synthesis and red blood cell production in the fetus and newborn 6Red blood cell lifespan and the red blood cell membrane in the fetus and neonate 9Red blood cell metabolism in the fetus and neonate 10Iron metabolism in the fetus and neonate 11Normal values for red blood cell parameters in the fetus and neonate 12Leucocytes in the fetus and newborn 17Leucocyte production and function in the fetus and neonate 18Platelets and megakaryocytes in the fetus and neonate 23Developmental megakaryopoiesis and thrombopoiesis 23Platelet numbers in the neonate and fetus – normal values 24Neonatal platelet function 25Practical problems in interpreting neonatal blood counts and films 25Sample quality/artefacts 25Site of sampling 26Gestational age and postnatal age 27Pregnancy-associated complications and mode of delivery 28References 282 Red cell disorders: Anaemia, jaundice, polycythaemia and cyanosis 38Neonatal anaemia 38Definition and clinical significance of neonatal anaemia 38Neonatal anaemia due to reduced red cell production 39Neonatal anaemia due to increased red cell destruction 47Neonatal anaemia due to haemoglobinopathies and other microcytic anaemias 67Neonatal anaemia due to blood loss 76Anaemia of prematurity 81A simple diagnostic approach to neonatal anaemia 83Neonatal polycythaemia 85Haematological causes of cyanosis 86Principles of red cell transfusion in neonates 86Illustrative cases 88Abbreviations used in the illustrative cases 110References 1103 Neonatal infection and leucocyte disorders 128Leucocyte abnormalities in neonatal systemic disease 128Increases in leucocyte numbers 128Neonatal infection and its differential diagnosis: clues from the blood count and blood film 135Storage disorders: diagnostic clues from the blood film 144Neonatal neutropenia 145Definition and causes of neutropenia 145Immune neutropenia 148Inherited congenital or neonatal neutropenia 150Haematological features of neonates with Down syndrome 154Congenital leukaemia 154Leukaemia and preleukaemia in neonates with Down syndrome 156Acute leukaemia in neonates without Down syndrome 160Juvenile myelomonocytic leukaemia and Noonan syndrome myeloproliferative disorder 168Illustrative cases 169Abbreviations used in the illustrative cases 176References 1764 Disorders of platelets and coagulation, thrombosis and blood transfusion 190Thrombocytopenia overview 190Causes of neonatal thrombocytopenia: a practical classification based on age at onset 192Fetal thrombocytopenia 194Early-onset neonatal thrombocytopenia (presenting at <72 hours of age) 194Late-onset neonatal thrombocytopenia (presenting at >72 hours of age) 196Conditions leading to clinically significant thrombocytopenia in the neonate 197Fetal/neonatal alloimmune thrombocytopenia 197Neonatal thrombocytopenia due to maternal autoimmune disease 200Thrombocytopenia due to congenital infections 201Neonatal thrombocytopenia associated with chromosomal abnormalities 205Inherited thrombocytopenia 206Investigation of neonatal thrombocytopenia 215Management of neonatal thrombocytopenia 215Indications for platelet transfusion 216Platelet function disorders 217Inherited platelet function disorders with normal platelet counts presenting in the neonate 218Thrombocytosis 218Abnormalities of coagulation 220Developmental haemostasis 220Laboratory investigation of coagulation disorders in the neonate 220Acquired coagulation abnormalities 221Inherited coagulation disorders 223Thrombosis 224Screening tests for thrombophilia in neonates 224Acquired thrombotic abnormalities 225Inherited thrombotic abnormalities 225General principles of neonatal platelet and plasma component transfusion 226Platelet transfusion 226Fresh frozen plasma 226Cryoprecipitate 227Prothrombin complex and recombinant factor VIIa 227Illustrative cases 227Abbreviations used in the illustrative cases 233References 234Index 254

Irene Roberts is Emeritus Professor of Paediatric Haematology at the Department of Paediatrics and MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford. She was formerly Professor of Paediatric Haematology at Imperial College London and Honorary Consultant Paediatric Haematologist at St Mary’s and Hammersmith Hospitals, Imperial College Healthcare NHS Trust where she established a neonatal haematology diagnostic service based on daily evaluation of peripheral blood films over several decades. Her research focuses on the molecular and biological characteristics of blood disorders in the fetus and early childhood particularly in Down syndrome. Barbara J. Bain is a Professor of Diagnostic Haematology at St Mary’s Hospital Campus, Imperial College Faculty of Medicine. She is also a Consultant Haematologist at St Mary’s Hospital, London, UK. Her research has been focused on morphology of blood cells, ethnic and biological differences in haematological variables and cytogenetics and molecular genetics in relation to haematological malignancy. She has collaborated with numerous experts in the field and contributed to the WHO Classification of Tumours of Haemopoietic and Lymphoid Tissues.

• Preface viiiAbbreviations x1 The full blood count and blood film in healthy term and preterm neonates 1Introduction 1Brief outline of the ontogeny of haemopoiesis 1Properties of fetal haemopoietic stem and progenitor cells 2Red blood cell production and development in the fetus and neonate 5Erythropoietin production in the fetus and neonate 6Haemoglobin synthesis and red blood cell production in the fetus and newborn 6Red blood cell lifespan and the red blood cell membrane in the fetus and neonate 9Red blood cell metabolism in the fetus and neonate 10Iron metabolism in the fetus and neonate 11Normal values for red blood cell parameters in the fetus and neonate 12Leucocytes in the fetus and newborn 17Leucocyte production and function in the fetus and neonate 18Platelets and megakaryocytes in the fetus and neonate 23Developmental megakaryopoiesis and thrombopoiesis 23Platelet numbers in the neonate and fetus – normal values 24Neonatal platelet function 25Practical problems in interpreting neonatal blood counts and films 25Sample quality/artefacts 25Site of sampling 26Gestational age and postnatal age 27Pregnancy-associated complications and mode of delivery 28References 282 Red cell disorders: Anaemia, jaundice, polycythaemia and cyanosis 38Neonatal anaemia 38Definition and clinical significance of neonatal anaemia 38Neonatal anaemia due to reduced red cell production 39Neonatal anaemia due to increased red cell destruction 47Neonatal anaemia due to haemoglobinopathies and other microcytic anaemias 67Neonatal anaemia due to blood loss 76Anaemia of prematurity 81A simple diagnostic approach to neonatal anaemia 83Neonatal polycythaemia 85Haematological causes of cyanosis 86Principles of red cell transfusion in neonates 86Illustrative cases 88Abbreviations used in the illustrative cases 110References 1103 Neonatal infection and leucocyte disorders 128Leucocyte abnormalities in neonatal systemic disease 128Increases in leucocyte numbers 128Neonatal infection and its differential diagnosis: clues from the blood count and blood film 135Storage disorders: diagnostic clues from the blood film 144Neonatal neutropenia 145Definition and causes of neutropenia 145Immune neutropenia 148Inherited congenital or neonatal neutropenia 150Haematological features of neonates with Down syndrome 154Congenital leukaemia 154Leukaemia and preleukaemia in neonates with Down syndrome 156Acute leukaemia in neonates without Down syndrome 160Juvenile myelomonocytic leukaemia and Noonan syndrome myeloproliferative disorder 168Illustrative cases 169Abbreviations used in the illustrative cases 176References 1764 Disorders of platelets and coagulation, thrombosis and blood transfusion 190Thrombocytopenia overview 190Causes of neonatal thrombocytopenia: a practical classification based on age at onset 192Fetal thrombocytopenia 194Early-onset neonatal thrombocytopenia (presenting at <72 hours of age) 194Late-onset neonatal thrombocytopenia (presenting at >72 hours of age) 196Conditions leading to clinically significant thrombocytopenia in the neonate 197Fetal/neonatal alloimmune thrombocytopenia 197Neonatal thrombocytopenia due to maternal autoimmune disease 200Thrombocytopenia due to congenital infections 201Neonatal thrombocytopenia associated with chromosomal abnormalities 205Inherited thrombocytopenia 206Investigation of neonatal thrombocytopenia 215Management of neonatal thrombocytopenia 215Indications for platelet transfusion 216Platelet function disorders 217Inherited platelet function disorders with normal platelet counts presenting in the neonate 218Thrombocytosis 218Abnormalities of coagulation 220Developmental haemostasis 220Laboratory investigation of coagulation disorders in the neonate 220Acquired coagulation abnormalities 221Inherited coagulation disorders 223Thrombosis 224Screening tests for thrombophilia in neonates 224Acquired thrombotic abnormalities 225Inherited thrombotic abnormalities 225General principles of neonatal platelet and plasma component transfusion 226Platelet transfusion 226Fresh frozen plasma 226Cryoprecipitate 227Prothrombin complex and recombinant factor VIIa 227Illustrative cases 227Abbreviations used in the illustrative cases 233References 234Index 254