Neonatal Haematology

Preface viii

Abbreviations x

1 The full blood count and blood film in healthy term and preterm neonates 1

Introduction 1

Brief outline of the ontogeny of haemopoiesis 1

Properties of fetal haemopoietic stem and progenitor cells 2

Red blood cell production and development in the fetus and neonate 5

Erythropoietin production in the fetus and neonate 6

Haemoglobin synthesis and red blood cell production in the fetus and newborn 6

Red blood cell lifespan and the red blood cell membrane in the fetus and neonate 9

Red blood cell metabolism in the fetus and neonate 10

Iron metabolism in the fetus and neonate 11

Normal values for red blood cell parameters in the fetus and neonate 12

Leucocytes in the fetus and newborn 17

Leucocyte production and function in the fetus and neonate 18

Platelets and megakaryocytes in the fetus and neonate 23

Developmental megakaryopoiesis and thrombopoiesis 23

Platelet numbers in the neonate and fetus - normal values 24

Neonatal platelet function 25

Practical problems in interpreting neonatal blood counts and films 25

Sample quality/artefacts 25

Site of sampling 26

Gestational age and postnatal age 27

Pregnancy-associated complications and mode of delivery 28

References 28

2 Red cell disorders: Anaemia, jaundice, polycythaemia and cyanosis 38

Neonatal anaemia 38

Definition and clinical significance of neonatal anaemia 38

Neonatal anaemia due to reduced red cell production 39

Neonatal anaemia due to increased red cell destruction 47

Neonatal anaemia due to haemoglobinopathies and other microcytic anaemias 67

Neonatal anaemia due to blood loss 76

Anaemia of prematurity 81

A simple diagnostic approach to neonatal anaemia 83

Neonatal polycythaemia 85

Haematological causes of cyanosis 86

Principles of red cell transfusion in neonates 86

Illustrative cases 88

Abbreviations used in the illustrative cases 110

References 110

3 Neonatal infection and leucocyte disorders 128

Leucocyte abnormalities in neonatal systemic disease 128

Increases in leucocyte numbers 128

Neonatal infection and its differential diagnosis: clues from the blood count and blood film 135

Storage disorders: diagnostic clues from the blood film 144

Neonatal neutropenia 145

Definition and causes of neutropenia 145

Immune neutropenia 148

Inherited congenital or neonatal neutropenia 150

Haematological features of neonates with Down syndrome 154

Congenital leukaemia 154

Leukaemia and preleukaemia in neonates with Down syndrome 156

Acute leukaemia in neonates without Down syndrome 160

Juvenile myelomonocytic leukaemia and Noonan syndrome myeloproliferative disorder 168

Illustrative cases 169

Abbreviations used in the illustrative cases 176

References 176

4 Disorders of platelets and coagulation, thrombosis and blood transfusion 190

Thrombocytopenia overview 190

Causes of neonatal thrombocytopenia: a practical classification based on age at onset 192

Fetal thrombocytopenia 194

Early-onset neonatal thrombocytopenia (presenting at

Late-onset neonatal thrombocytopenia (presenting at >72 hours of age) 196

Conditions leading to clinically significant thrombocytopenia in the neonate 197

Fetal/neonatal alloimmune thrombocytopenia 197

Neonatal thrombocytopenia due to maternal autoimmune disease 200

Thrombocytopenia due to congenital infections 201

Neonatal thrombocytopenia associated with chromosomal abnormalities 205

Inherited thrombocytopenia 206

Investigation of neonatal thrombocytopenia 215

Management of neonatal thrombocytopenia 215

Indications for platelet transfusion 216

Platelet function disorders 217

Inherited platelet function disorders with normal platelet counts presenting in the neonate 218

Thrombocytosis 218

Abnormalities of coagulation 220

Developmental haemostasis 220

Laboratory investigation of coagulation disorders in the neonate 220

Acquired coagulation abnormalities 221

Inherited coagulation disorders 223

Thrombosis 224

Screening tests for thrombophilia in neonates 224

Acquired thrombotic abnormalities 225

Inherited thrombotic abnormalities 225

General principles of neonatal platelet and plasma component transfusion 226

Platelet transfusion 226

Fresh frozen plasma 226

Cryoprecipitate 227

Prothrombin complex and recombinant factor VIIa 227

Illustrative cases 227

Abbreviations used in the illustrative cases 233

References 234

Index 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.

I. Roberts, University of Oxford, UK; B. J. Bain, St Mary's Hospital, London, UK