Alloimmune Disorders of Pregnancy: Anaemia, Thrombocytopenia and Neutropenia in the Fetus and Newborn

, by Edited by Andrew Hadley , Peter Soothill

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ISBN: 9780521018043 | 0521018048
Cover: Paperback
Copyright: 8/22/2005

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Collectively known as the alloimmune cytopenias, hemolytic disease of the fetus and newborn, alloimmune thrombocytopenia and alloimmune neutropenia are all consequences of maternal immunisation to fetal blood cells. The effective prevention, diagnosis and management of these disorders has become a team effort involving haematologists, obstetricians, paediatricians, immunologists, laboratory technicians, midwives and research scientists. This book has been written by experts in their respective fields to bring together the issues of pathogenesis, epidemiology, prevention, diagnosis and clinical management. This comprehensive but accessible account is extensively cross-referenced to emphasise the links between pathogenesis and clinical sequelae, between epidemiology and the rationale for screening programmes, and between diagnosis and therapeutic intervention. This is an authoritative overview suitable for trainees in obstetrics, materno-fetal medicine, transfusion medicine and clinical immunology.

List of contributors

Preface

xvii

Foreword

xix

List of abbreviations

xxi

1 Pathophysiology of the alloimmune cytopenias

(20)

Andrew G Hadley and Craig Turner

1.1 Maternal alloimmunization

(5)

1.1.1 Some key events in the humoral immune response

(3)

1.1.2 The maternal alloimmune response to fetal red cells

(1)

1.1.3 The maternal alloimmune response to fetal platelets

(1)

1.1.4 The maternal alloimmune response to fetal neutrophils

(1)

1.2 Transfer of IgG to the fetus

(1)

1.3 The immune destruction of blood cells in the fetus

(7)

1.3.1 IgG and Fcy receptors

(1)

1.3.2 The immune destruction of fetal red cells

(4)

1.3.3 The immune destruction of fetal platelets

(2)

1.3.4 The immune destruction of fetal neutrophils

(1)

1.4 Conclusions

(1)

1.5 References

(7)

2 Blood group antibodies in haemolytic disease of the fetus and newborn

(20)

Geoff Daniels

2.1 Introduction

(1)

2.2 Blood group terminology

(3)

2.3 The genetics of blood groups

(1)

2.4 The effect of antigen expression on the pathogenicity and severity of HDFN

(2)

2.5 Antibodies that most commonly cause moderate or severe HDFN

(6)

2.5.1 Anti-D

(3)

2.5.2 Other antibodies to Rh-system antigens

(1)

2.5.3 Anti-K

(1)

2.5.4 Other antibodies to Kell-system antigens

(1)

2.6 Antibodies that most commonly cause mild HDFN

(1)

2.6.1 The ABO system

(1)

2.7 Antibodies that rarely cause HDFN

(2)

2.7.1 MNS system

(1)

2.7.2 Duffy system

(1)

2.7.3 Kidd system

(1)

2.7.4 Diego system

(1)

2.7.5 Colton system

(1)

2.7.6 Other antigens

(1)

2.8 Antibodies that do not cause HDFN

(1)

2.9 Conclusions

(1)

2.10 References

(4)

3 Basis and practice of screening for haemolytic disease of the fetus and newborn

(20)

Geoff Poole

3.1 Introduction

(1)

3.2 The basis of screening for HDFN

(1)

3.3 Antenatal screening tests performed in the blood transfusion laboratory

(8)

3.3.1 Antiglobulin methods

(4)

3.3.2 Enzyme methods

(1)

3.3.3 The choice of red cells for screening tests

(1)

3.3.4 Manual versus automated methods

(1)

3.3.5 Timing of screening tests

(1)

3.4 The identification of red cell alloantibodies

(6)

3.4.1 Methods

(1)

3.4.2 The principles of antibody identification

(3)

3.4.3 Difficulties encountered in antibody identification

(1)

3.4.4 Implications of detecting a red cell alloantibody during pregnancy

(1)

3.5 Paternal and fetal phenotyping

(2)

3.5.1 Paternal phenotype

(1)

3.5.2 Fetal phenotype

(1)

3.6 Laboratory tests immediately following delivery

(1)

3.7 References

(3)

4 Epidemiology and screening for alloimmune thrombocytopenia

(12)

Lorna M Williamson and Michael F Murphy

4.1 Background

(1)

4.2 Epidemiology and the natural history of alloimmune thrombocytopenia

(2)

4.2.1 The incidence of maternal alloimmunization

(1)

4.2.2 The incidence of fetal thrombocytopenia due to maternal alloimmunization

(1)

4.2.3 The incidence of intracranial haemorrhage and other sequelae

(1)

4.2.4 The influence of obstetric history on clinical outcome

(1)

4.3 Criteria for antenatal screening for alloimmune thrombocytopenia

(5)

4.3.1 The condition should be an important health problem

(1)

4.3.2 The epidemiology of the condition should be known

(1)

4.3.3 The natural history of the condition should be understood

(1)

4.3.4 There should be a recognized latent period or early asymptomatic stage

(1)

4.3.5 All the cost-effective primary prevention interventions should have been implemented as far as practicable

(1)

4.3.6 There should be a simple, safe, precise and validated screening test

(1)

4.3.7 The distribution of test values in the target population should be known and a suitable cut-off level defined and agreed

(1)

4.3.8 The test should be acceptable to the population

(1)

4.3.9 There should be an agreed policy on the further diagnostic investigation of individuals with a positive result and on the choices available to those individuals

(1)

4.3.10 There should be an effective treatment or intervention for patients identified through early detection

(2)

4.3.11 There should be agreed evidence-based policies covering which individuals should be offered treatment and the appropriate treatment to be offered

(1)

4.3.12 Clinical management of the condition and patient outcomes should be optimized by all health providers prior to participation in a screening programme

(1)

4.4 The cost-effectiveness of a screening programme

(1)

4.5 Conclusions

(1)

4.6 References

(3)

5 Principles of antibody-mediated immune suppression and the prevention of maternal RhD alloimmunization

(24)

Belinda Kumpel

5.1 Haemolytic disease of the fetus and newborn due to anti-D

(1)

5.2 Experimental studies on the prevention of RhD immunization

(1)

5.3 Clinical studies on the efficacy of RhD prophylaxis

(3)

5.3.1 Dose of anti-D

(1)

5.3.2 The current situation

(1)

5.4 Characteristics and requirements of RhD prophylaxis

(3)

5.4.1 Ratio of antibody to antigen required for suppression

(1)

5.4.2 Relationship of red cell clearance to antibody-mediated immune suppression

(1)

5.4.3 Protection afforded by ABO antibodies

(1)

5.4.4 Role of the spleen in RhD prophylaxis

(1)

5.4.5 Timing of passive anti-D

(1)

5.4.6 Time of detection of anti-D response

(1)

5.4.7 Effect of passive anti-D on subsequent immunization

(1)

5.4.8 Effect of passive anti-D on an established primary response

(1)

5.4.9 Role of anti-D Fc fragments

(1)

5.4.10 Epitope specificity

(1)

5.5 Theories of the mechanism of action of prophylactic anti-D

(3)

5.5.1 Inhibition of B cells by crosslinking heterologous receptors

(2)

5.5.2 Anti-idiotypic antibodies

(1)

5.5.3 Masking of antigen sites

(1)

5.5.4 Clearance and destruction of D-positive red cells

(1)

5.6 Development of monoclonal anti-D for RhD prophylaxis

(4)

5.6.1 Production of monoclonal anti-D

(1)

5.6.2 Half-lives of monoclonal anti-D

(1)

5.6.3 In vitro functional activity of monoclonal anti-D

(1)

5.6.4 In vivo red cell clearance mediated by monoclonal anti-D

(2)

5.6.5 Suppression of the anti-D response by monoclonal anti-D

(1)

5.7 References

(9)

6 The clinical application of anti-D prophylaxis

(24)

Stan Urbaniak

6.1 Epidemiology

(1)

6.1.1 Causes and incidence of alloimmunization

(1)

6.1.2 Ethnic groups

(1)

6.1.3 Use of D-negative transfusions for young women

(1)

6.1.4 Relative importance of anti-D before and after the introduction of anti-D prophylaxis programmes

(1)

6.2 Prophylaxis programmes

(7)

6.2.1 Suppression of the immune response

(1)

6.2.2 Recommendations and guidelines

(2)

6.2.3 Effectiveness in Caucasian populations

101

(1)

6.2.4 Reasons for continued failures

101

(1)

6.2.5 Anti-D immunization during pregnancy

102

(1)

6.2.6 Antenatal administration of anti-D immunoglobulin

102

(2)

6.2.7 Anti-D immunoglobulin use on women with weak D or partial D

104

(1)

6.2.8 Anti-D immunoglobulin use after the accidental transfusion of D-positive red cells

104

(1)

6.3 Detection of fetal red cells in the maternal circulation

105

(3)

6.3.1 The Kleihauer–Betke acid-elution test

106

(1)

6.3.2 Flow cytometry

106

(1)

6.3.3 Serological tests of fetomaternal haemorrhage

107

(1)

6.3.4 Calculating the size of fetomaternal haemorrhage

107

(1)

6.4 Fetomaternal haemorrhage and dose of anti-D immunoglobulin

108

(4)

6.4.1 Fetomaternal haemorrhage at delivery

108

(1)

6.4.2 Bleeding during pregnancy

108

(1)

6.4.3 Spontaneous fetomaternal haemorrhage during first, second and third trimesters

109

(1)

6.4.4 Other significant events during pregnancy

110

(1)

6.4.5 Fetomaternal haemorrhage due to medical procedures

110

(1)

6.4.6 Calculation of the required dose of anti-D

111

(1)

6.5 Procurement of hyperimmune anti-D

112

(2)

6.5.1 Identification, recruitment, boosting and accreditation of donors

112

(1)

6.5.2 Manufacture of anti-D immunoglobulin and safety considerations

113

(1)

6.6 Economics of prophylaxis programmes

114

(1)

6.6.1 Cost-effectiveness of antenatal versus postnatal prophylaxis

114

(1)

6.7 Future developments

115

(1)

6.8 References

116

(5)

7 Fetal genotyping

121

(20)

Neil D Avent

7.1 Introduction

121

(1)

7.2 The polymerase chain reaction

121

(3)

7.2.1 Principle of the polymerase chain reaction

121

(1)

7.2.2 Polymerase chain reaction – restriction fragment length polymorphism analysis

122

(1)

7.2.3 Allele-specific primer amplification

122

(2)

7.3 PCR-based typing for clinically significant blood groups

124

(9)

7.3.1 The Rh system

125

(5)

7.3.2 Kell system

130

(1)

7.3.3 Duffy system

131

(1)

7.3.4 Kidd system

132

(1)

7.3.5 ABO system

132

(1)

7.4 Noninvasive testing

133

(1)

7.4.1 Detection of fetal RHD targets in genomic DNA extracted from fetal leukocytes in maternal blood

133

(1)

7.4.2 The detection of fetal RhD cDNA derived from RNA extracted from maternal blood

133

(1)

7.4.3 Detection of fetal RHD targets in genomic DNA extracted from maternal plasma

134

(1)

7.5 Future perspectives

134

(1)

7.6 References

135

(6)

8 Laboratory assays to determine the severity of haemolytic disease of the fetus and newborn

141

(32)

Andrew G Hadley

8.1 Introduction

141

(1)

8.2 Serological assays

141

(3)

8.3 Quantitative assays

144

(1)

8.4 Cellular assays

144

(4)

8.4.1 The K lymphocyte-mediated ADCC assay

145

(1)

8.4.2 The monocyte-mediated ADCC assay

146

(1)

8.4.3 The monocyte monolayer assay

146

(1)

8.4.4 The chemiluminescence test

147

(1)

8.5 A strategy for antenatal testing

148

(1)

8.6 References

149

(4)

9 Assessing the severity of haemolytic disease of the fetus and newborn: clinical aspects

153

(20)

Sherif Abdel-Fattah and Peter Soothill

9.1 Introduction

153

(1)

9.2 Noninvasive assessment

153

(10)

9.2.1 Previous obstetric history

153

(1)

9.2.2 Antibody levels

154

(2)

9.2.3 Ultrasound findings

156

(2)

9.2.4 Fetal heart rate monitoring

158

(1)

9.2.5 Fetal Doppler ultrasonography

159

(4)

9.3 Invasive testing

163

(4)

9.3.1 Amniocentesis

163

(2)

9.3.2 Fetal blood sampling

165

(2)

9.4 Conclusions

167

(1)

9.5 References

167

(6)

10 Antenatal therapy for haemolytic disease of the fetus and newborn

173

(30)

Kenneth 1 Moise Jr and Paul W Whitecar

10.1 Introduction

173

(1)

10.2 Plasmapheresis and intravenous immune globulin

173

(5)

10.2.1 Plasmapheresis

173

(2)

10.2.2 Intravenous immunoglobulin

175

(3)

10.3 Intrauterine transfusion

178

(10)

10.3.1 History

178

(1)

10.3.2 Access site

179

(1)

10.3.3 Method of transfusion

180

(1)

10.3.4 Amount to transfuse

181

(2)

10.3.5 The severely anaemic fetus

183

(1)

10.3.6 Adjunctive measures

183

(1)

10.3.7 Outcome

184

(4)

10.4 Red cells for transfusion

188

(2)

10.5 Experimental therapy

190

(3)

10.5.1 Immunoabsorption

190

(1)

10.5.2 Oral tolerance

191

(1)

10.5.3 Chemotherapeutic agents

191

(1)

10.5.4 Sensitization to paternal leukocyte antigens

192

(1)

10.6 Timing of delivery

193

(1)

10.7 Conclusion

193

(1)

10.8 References

193

(10)

11 Neonatal therapy for haemolytic disease of the newborn

203

(16)

Glynn Russell and Nic Goulden

11.1 Features of haemolytic disease in the neonate

203

(1)

11.1.1 Hydrops

203

(1)

11.1.2 Neonatal jaundice

204

(1)

11.1.3 Persistent anaemia

204

(1)

11.2 Laboratory diagnosis

204

(1)

11.3 General neonatal management

205

(1)

11.3.1 Communication

205

(1)

11.3.2 Resuscitation

205

(1)

11.4 Treatment of hydrops

206

(1)

11.5 Treatment of anaemia

206

(4)

11.5.1 Blood transfusion

206

(3)

11.5.2 Influence of fetal transfusions

209

(1)

11.5.3 Indications for transfusion

209

(1)

11.6 Treatment of neonatal jaundice

210

(4)

11.6.1 Phototherapy

210

(1)

11.6.2 Exchange blood transfusion

210

(2)

11.6.3 An integrated approach to treating neonatal jaundice

212

(2)

11.7 Experimental treatments

214

(1)

11.8 References

214

(5)

12 The diagnosis of alloimmune thrombocytopenia

219

(16)

Andrew G Hadley

12.1 Clinical aspects of diagnosis

219

(1)

12.2 Platelet antigen systems

220

(1)

12.2.1 Platelet antigens on glycoprotein IIb/IIIa

220

(1)

12.2.2 Platelet antigens on glycoprotein Ia/IIa

221

(1)

12.2.3 Platelet antigens on glycoprotein Ib/IX/V

221

(1)

12.3 Platelet antibody specificities involved in alloimmune thrombocytopenia

221

(3)

12.4 Laboratory diagnosis of alloimmune thrombocytopenia

224

(4)

12.4.1 Haematology

224

(1)

12.4.2 Assays for the detection of antiplatelet antibodies

225

(2)

12.4.3 DNA-based genotyping

227

(1)

12.4.4 Antibody characteristics and disease severity

228

(1)

12.5 Future perspectives

228

(1)

12.6 References

229

(6)

13 The immunological diagnosis of alloimmune neutropenia

235

(18)

Geoff Lucas

13.1 Introduction

235

(1)

13.2 Pathophysiology and clinical history

235

(3)

13.2.1 Immunogenicity of fetal neutrophils

235

(1)

13.2.2 Clinical manifestations and haematological findings

235

(1)

13.2.3 Differential diagnosis

236

(2)

13.3 The structure and function of antigens involved in alloimmune neutropenia

238

(7)

13.3.1 Nomenclature

238

(1)

13.3.2 Granulocyte-specific antigens

239

(4)

13.3.3 'Shared' antigens

243

(1)

13.3.4 Antibody specificities involved in alloimmune neutropenia

244

(1)

13.3.5 The function of granulocyte antigens

244

(1)

13.4 Laboratory diagnosis of alloimmune neutropenia

245

(3)

13.4.1 Assays for granulocyte antibodies

245

(2)

13.4.2 Role of crossmatching and parental typing

247

(1)

13.4.3 Granulocyte antigen typing

247

(1)

13.5 References

248

(5)

14 Fetal and neonatal treatment of alloimmune thrombocytopenia

253

(26)

Michael F Murphy, Rachel Rayment, David Allen and David Roberts

14.1 Introduction

253

(1)

14.2 Neonatal management of alloimmune thrombocytopenia

254

(3)

14.2.1 Platelet transfusion

254

(2)

14.2.2 Intravenous immunoglobulin

256

(1)

14.2.3 Monitoring of the effectiveness of neonatal treatment

257

(1)

14.3 Antenatal management of alloimmune thrombocytopenia

257

(13)

14.3.1 Fetal blood sampling

258

(1)

14.3.2 Maternal treatment

259

(4)

14.3.3 Fetal platelet transfusion

263

(4)

14.3.4 Serial fetal platelet transfusions compared with maternal administration of high-dose intravenous immunoglobulin

267

(1)

14.3.5 Timing of the initial fetal blood sample

268

(1)

14.3.6 Strategy for the antenatal management of pregnancies at risk of very early intracranial haemorrhage

269

(1)

14.4 Preparation of platelet concentrates for transfusion in cases of alloimmune thrombocytopenia

270

(2)

14.4.1 Provision of HPA-typed platelets for neonates with alloimmune thrombocytopenia

270

(1)

14.4.2 Identification and recruitment of HPA- la-negative and HPA-5b-negative donors

270

(1)

14.4.3 Preparation of platelet concentrates for fetal transfusions

271

(1)

14.5 Future directions

272

(2)

14.6 References

274

(5)

Index

279

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Alloimmune Disorders of Pregnancy: Anaemia, Thrombocytopenia and Neutropenia in the Fetus and Newborn

Summary

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Table of Contents

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