Neonatology and Blood Transfusion (eBook)

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

"II. IMMUNOHAEMATOLOGY AND HAEMOSTASIS MANAGEMENT OF RED CELL ALLOIMMUNIZATION IN PREGNANCY (p. 68-67)

I.L. van Kamp, H.H.H. Kanhai

History of Red Cell Alloimmunization

Haemolytic disease of the foetus and newborn, also known as erythroblastosis foetalis, used to be one of the main causes of perinatal mortality for many centuries. Although the clinical picture of extremely hydropic and icteric stillborns was already described in the 17 century, the pathogenesis of the disease was not understood until the early 1940s.

Darrow published in 1934 an extensive overview on the clinical picture and etiologic considerations of neonatal haemolytic disease [1]. From the observation that the disease frequently occurred in the offspring in one family, Darrow hypothesized that the placenta may be the means of transmission of a destructive influence from mother to foetus [1]. Subsequently, Levine and Stetson managed to identify an unknown red-cell antigen in the blood of a woman who was delivered from a stillborn hydropic baby [2].

The woman had massive uterine bleeding and appeared to suffer from a life-threatening transfusion reaction, after being transfused with her husbands f blood. As husband and wife both had blood type 0, Levine and Stetson called this unknown phenomenon “intra-group agglutination” [2,3]. Simultaneously, Landsteiner and Weiner discovered an agglutinating factor in th serum of rodents, sensitised with blood from a Macacus Rhesus monkey [4]. As this factor caused agglutination of the blood of 85% of New York’s population, it was f initially assumed to be similar to the human antibody causing erythroblastosis foetalis.

Eventually, the antibody appeared comparable, though not identical to the human antibody, but by that time it had been erroneously called “Rhesus”. t After the discovery of the alloimmune origin of haemolytic disease, more insight and knowledge was gained on this pathological process by several studies [5]. In these years a beneficial effect of maternal and pater f nal ABO incompati- r bility on the severity of haemolytic disease was observed [6].

Neonatal exchange transfusion as a method of treatment of hyperbilirubinaemia was described by Wallerstein in 1946 [7]. This was the first impor tant step in the prevention of kernicterus, the most serious and feared complication of neonatal hyperbilirubinaemia, followed in 1958 by the introduction of fototherapy. However, until the 1960s severe foetal haemolytic disease could neither be diagnosed nor be treated. Elective preterm delivery of a foetus, assumed to be viable, was the policy in most pregnancies complicated by maternal Rhesus (D) alloimmunization, aiming to prevent foetal demise and to be able to start neonatal treatment."