Neonatology and Blood Transfusion : Proceedings of the Twenty-Eighth International Symposium on Blood Transfusion, Groningen, NL Organized by the Sanquin Division Blood Bank Noord Nederland

**Neonatology and Blood Transfusion** __Proceedings of the Twenty-Eighth International Symposium on Blood Transfusion, Groningen, NL, Organized by the Sanquin Division Blood Bank North-East, Groningen__ It is in many ways fitting that the last of these international symposia on blood transfusion should end with neonatal blood transfusion. The most fragile, least well studied and most at risk population requires special care and concern. We need to expand our knowledge of their unique physiology, biochemical pathways and in planning treatment and interventions, always "do no harm." This proceedings of the last Groningen symposium presents a wealth of information on developmental immunology, the molecular basis of haematopoeisis, physiological basis of bleeding and thrombosis, transfusion risks and benefits and lastly, future therapies. Infants provide us with much to learn but in turn they will be the providers of (through cord blood) and the recipients of (through cellular engineering) the best that science can offer. Translational research, which has been the thrust of these presentations for 28 years, will benefit them in a way that no scientist could have ever predicted. Title Page 4 Copyright Page 5 INTRODUCTION 7 Table of Contents 8 MODERATORS AND SPEAKERS 10 OPENING ADDRESS 12 I. FOETAL AND NEONATAL HAEMATOLOGY 15 REGULATION OF DEVELOPMENTAL HAEMATOPOIESIS BY GATA TRANSCRIPTION FACTORS1 16 Introduction 16 Biology of ‘haematopoietic’ GATA transcription factors 17 Developmental changes in haematopoiesis 20 GATA transcription factors in the switch from ‘primitive’ to ‘definitive’ haematopoiesis 20 GATA transcription factors in the switch of the primary site of haematopoiesis 21 GATA transcription factors in developmental changes of the proliferative activity of haematopoietic progenitor cells 23 Regulation of the Epo receptor by GATA-1 in haematopoietic progenitor cells 23 Role of GATA transcription factors in the switch of globin genes during development 24 GATA transcription factors in the regulation of the switch of primary site of erythropoietin production 25 GATA transcription factors in congenital or acquired disorders of haematopoiesis 26 Human disorders linked to cis-acting GATA sequences 28 Summary 28 Acknowledgement 29 References 29 DEVELOPMENT OF THE IMMUNE SYSTEM IN THE FOETAL AND PERINATAL PERIOD 37 References 41 FOETAL AND NEONATAL IMMUNOHAEMATOLOGICAL RESPONSES: CONSEQUENCES FOR PRACTICAL MANAGEMENT? 43 Introduction 43 Foetal and Neonatal Transfusions 44 Long-Term Effects of Intraperitoneal Transfusions with Non-Leukocyte Reduced, Non-Irradiated Red Cells 44 Effects of Maternally Administered High Dose Immunoglobulin (IVIG) and Platelet Transfusions (IUPT) in Infant Hood 46 Short Term Effects of Intrauterine Erythrocyte Transfusions (despite leukocyte reduction and gamma irradiation) 47 Immediate Effects of IUET 50 Premature Infants 50 Conclusion 52 References 53 BIOLOGY OF THROMBOPOIETIN IN THE HUMAN FOETUS AND NEONATE 55 Introduction 55 Discovery and terminology of thrombopoietin and its receptor c-mpl 55 Cellular biology of thrombopoietin 55 Molecular biology of thrombopoietin 56 Molecular biology of c-mpl, the thrombopoietin receptor 57 Regulation of Tpo 58 Clinical biology of Tpo 59 Biology of thrombopoietin in inherited neonatal thrombocytopenias 60 Biology of thrombopoietin in acquired neonatal thrombocytopenias 62 Towards a rational to treat neonatal thrombocytopenia in sick preterm and term neonates 64 New aspects of the developmental biology of thrombopoietin 64 Acknowledgement 65 References 66 DISCUSSION 75 II. IMMUNOHAEMATOLOGY AND HAEMOSTASIS 81 MANAGEMENT OF RED CELL ALLOIMMUNIZATION IN PREGNANCY 82 History of Red Cell Alloimmunization 82 Prevention of Red Cell Immunisation 84 Maternal Serum Testing 86 Paternal Zygosity and Foetal Typing 87 Obstetric History 88 Plasmapheresis 88 Immunoglobulin in Red Cell Alloimmunization 89 Foetal monitoring 89 Intrauterine Transfusion 94 References 102 NEW TREATMENT OPTIONS IN NEONATAL HYPERBILIRUBINAEMIA 126 Introduction 126 Pathophysiology 127 Risk of Severe Hyperbilirubinaemia 128 Treatment of Unconjugated Hyperbilirubinaemia 129 Phototherapy 130 Mechanism of Action 130 Exchange Transfusion 134 Pharmacological Approach 135 Summary 135 References 136 CONSENSUS AND CONTROVERSY IN FOETAL AND NEONATAL ALLOIMMUNE THROMBOCYTOPENIA 140 Areas of Consensus 140 Antenatal Management 143 Maternally-administered Intravenous (IV) Gammaglobulin (IVIG) 144 Antenatal Treatment 147 Foetal Platelet Transfusions 149 Management of the Neonate 151 Conclusion 152 References 152 THE BLEEDING INFANT 155 Introduction 155 Investigation of the Neonate 156 Well Infant 156 Sick Infant 157 Gastrointestinal Bleeding 157 Intracranial Haemorrhage 157 Vitamin K Deficiency 157 Congenital Hereditary Syndromes 158 References 158 DISCUSSION 160 III. BLOOD TRANSFUSION IN THE NEONATE 173 NEONATAL THROMBOSIS 174 Introduction 174 Developmental Haemostasis 174 Risk Factors 175 Venous TEs 176 Arterial TEs 176 Renal Vein Thrombosis 177 Diagnosis 177 Laboratory Testing 177 Treatment 178 Summary 179 References 179 CRITERIA FOR SELECTING A RED BLOOD CELL PRODUCT TO TRANSFUSE ANAEMIC INFANTS 181 Introduction 181 Concerns About and Rationale for Transfusing Stored RBCs 182 Increase in Extracellular Potassium 182 Decrease in 2,3-DPG 183 Safety of Additives in Pre1ervative Solutions 183 Clinical Experience Transfusing Stored RBCs 185 Conclusions and Recommendations 187 References 187 HAZARDS OF TRANSFUSION: GvHD 189 History 189 Pathogenesis 189 Clinical Manifestations 191 Diagnosis of TA-GvHD 191 Microchimerism and its Relationship to TA-GvHD 192 Groups at Risk 192 The Irradiation Process 193 Instrumentation for Irradiation 194 Components to be Irradiated 195 Storage of Red Cells and Platelets after Irradiation 197 Selection of Radiation Dose 199 Quality Assurance Measures 200 Confirming that Irradiation Occurred 200 New Methods in the Prevention of TA-GvHD 202 Treatment of TA-GvHD 203 References 203 NON-IMMUNE, NON-INFECTIOUS COMPLICATIONS OF TRANSFUSION 210 Introduction 210 Extended Storage/Additive Solutions 211 Metabolic Complications 213 Potential Toxicities of Transfusion 217 References 219 EXTRACORPOREAL MEMBRANE OXYGENATION IN THE NEONATE WITH RESPIRATORY FAILURE 222 Introduction 222 ECMO Criteria 224 Pre-ECMO Procedures 225 The ECMO Procedure 225 Equipment and Systems 227 Patient Management 228 Daily Medical Management (Figure 5) 229 Outcome Data 231 Summary 232 References 232 DISCUSSION 236 IV. CELLULAR THERAPIES IN NEONATOLOGY 249 GENETIC ENGINEERING FOR THE FOETUS AND NEONATE 250 In Utero Haematopoietic Stem Cell Transplantation 250 Human IUHSCTx Clinical Trials 252 Gene Therapy for X-Linked Severe Combined Immune Deficiency 253 SCID Clinical Trials and Leukaemia 254 Future Directions 255 References 255 META-ANALYSIS AND EVIDENCE-BASED DECISION MAKING IN NEONATAL CARE 256 Introduction 256 Meta-analysis and Evidence-based Decisions in Neonatology 257 Pathophysiology of Erythropoietin in the Anaemia of Prematurity 258 Meta-Analysis of Clinical Trials Studying rHEPO in the Anaemia of Prematurity 259 Evidence-Based Medicine beyond Meta-Analysis for Making Medical Decisions 260 Conclusions 263 References 264 PLACENTAL BLOOD BANKING IN THE YEAR 2003 266 Introduction 266 The Milano Cord Blood Bank 268 Collection Centres 269 Donor Selection and Informed Consent 269 Exclusion Criteria 270 Cord Blood Collection, Transportation and Receipt at the Bank 270 Unit Processing, Characterisation and Quality Control 271 Cord Blood Cryopreservation 273 Cord Blood Unit Validation 274 Mother and Newborn Check Six Months after Delivery 275 Cord Blood Banking Process Monitoring 277 Conclusions 277 References 277 DISCUSSION 279 EPILOGUE 286 INDEX 287 Front Matter....Pages I-XV Front Matter....Pages 1-1 Regulation of Developmental Haematopoiesis By Gata Transcription Factors....Pages 3-23 Development of The Immune System In The Foetal and Perinatal Period....Pages 25-30 Foetal and Neonatal Immunohaematological Responses: Consequences for Practical Management?....Pages 31-42 Biology of Thrombopoietin In the Human Foetus and Neonate....Pages 43-62 Discussion....Pages 63-68 Front Matter....Pages 69-69 Management of Red Cell Alloimmunization in Pregnancy....Pages 71-114 New Treatment Options in Neonatal Hyperbilirubinaemia....Pages 115-128 Consensus and Controversy in Foetal and Neonatal Alloimmune Thrombocytopenia....Pages 129-143 The Bleeding Infant....Pages 145-149 Discussion....Pages 151-163 Front Matter....Pages 165-165 Neonatal Thrombosis....Pages 167-173 Criteria for Selecting a Red Blood Cell Product to Transfuse Anaemic Infants....Pages 175-182 Hazards of Transfusion: GvHD....Pages 183-203 Non-Immune, Non-Infectious Complications of Transfusion....Pages 205-216 Extracorporeal Membrane Oxygenation in the Neonate with Respiratory Failure....Pages 217-230 Discussion....Pages 231-243 Front Matter....Pages 245-245 Genetic Engineering for the Foetus and Neonate....Pages 247-252 Meta-Analysis and Evidence-Based Decision Making in Neonatal Care....Pages 253-262 Placental Blood Banking in the Year 2003....Pages 263-275 Discussion....Pages 277-283 Epilogue....Pages 285-285 Back Matter....Pages 287-294