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Preface v Therapeutic Cytapheresis 23 SUMMARY 23 Contributors vii REVIEW QUESTIONS 24 REFERENCES 25 UNIT 1 ADDITIONAL READINGS 25 AND BLOOD COMPONENTS 1 3 Blood Components: Preparation, Storage, and Transport 26 1 Blood Collection and Processing 1 27 Recruitment of Donors 2 Additive Solutions 28 Donor Registration 2 Blood Collection Sets 28 Uniform Donor History Questionnaire 2 30 Physical Assessment 3 Red Blood Cells 30 Hemoglobin/Hematocrit 3 Red Blood Cells Leukocytes Reduced 30 Temperature 7 Red Blood Cells Washed 31 Blood Pressure 7 Red Blood Cells Frozen or Red Blood Cells Pulse 7 Deglycerolized 31 Confidential Unit Exclusion 7 Red Blood Cells Rejuvenated and Red Blood Cells Consent 7 Rejuvenated Deglycerolized 32 Blood Collection 7 Plasma 32 Labeling and Identification 8 or Plasma Frozen within 24 Hours Selection of Vein and Arm Preparation 8 after Phlebotomy 32 Phlebotomy and Collection of Samples 9 Recovered Plasma 33 Care of the Donor 9 Plasma, Reduced 33 Donor Reactions 10 Cryoprecipitate 33 Donor Unit Processing 10 33 ABO 11 Granulocytes 34 Rh 11 Aliquoting 35 Detection of Unexpected to Red Cell 11 Irradiation of Blood Components 35 Serologic Test for Syphilis 11 Labeling Requirements 36 Infectious Disease Testing 11 ISBT 128 36 Special Donations 13 Storage of Blood Components 37 Autologous Donation 13 Transport of Blood Components 37 Directed Donation 14 Shipping Containers 39 Dedicated Donors 14 SUMMARY 39 Therapeutic Phlebotomy 14 REVIEW QUESTIONS 39 SUMMARY 15 REFERENCES 40 REVIEW QUESTIONS 15 REFERENCES 16

2 Automated Collection of Blood Products 17 UNIT 2 ENETIC AND MMUNOLOGIC RINCIPLES Brief History on the Separation of Blood 18 G I P 41 Separation by Centrifugation (Intermittent or Continuous Flow) 18 4 Genetics 41 Bowl Technology 18 Mitosis and Meiosis 42 Automated Blood Products 19 and Genotypes 45 Plasma 19 Inheritance Patterns 45 Platelets 20 Contribution of Blood Group Genetics to Red Blood Cells 21 the Field of Human Genetics 47 Granulocyte Concentrates 21 Population Genetics 47 Hematopoietic Progenitor Cells (Stem Cells) 21 Linkage 48 Impacts of Automated Blood Collections 22 Crossing-Over and Recombination 48 Therapeutic Uses of 23 Positional or Modifier Effects of 49 Methodologies 23 Action 49 Therapeutic 23

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Silent Genes 49 Paroxysmal Cold Hemoglobinuria 87 Blood Group Nomenclature 50 Cold Agglutinin Disease 87 Public and Private Genes 50 Diamond-Blackfan Anemia 88 Blood Group Genes as Genetic Markers 50 Drug-induced Immune Hemolytic Anemia 88 SUMMARY 51 Unexpected Reactivity Not Due to Red REVIEW QUESTIONS 51 Cell Antibodies 90 REFERENCES 52 Integration of Serologic and Molecular Testing 91 ADDITIONAL READINGS 52 Clinical Relevance of Red Cell Alloantibodies 91 SUMMARY 92 5 Basic Immunologic Principles 53 REVIEW QUESTIONS 92 Cellular and Humoral Immunity 54 REFERENCES 92 Leukocytes: Cells of the Immune System 54 ADDITIONAL READINGS 94 Macrophages 55 Lymphocytes and Specific Binding by 7 Molecular Testing for Blood Groups in Cell Surface Receptors 56 95 T Lymphocytes 56 From DNA to Blood Groups 96 Immunogens versus Antigens 61 The Language of Genes 96 Route of Administration 61 Essentials of a Gene 96 Shape and Charge 61 Molecular Bases of Blood Groups 97 Antibodies 62 Applications of Molecular Analysis 98 Structure and Physiochemistry 62 Techniques Used to Predict a Blood Group IgG Subclass and Function 65 Antigen 99 Hybridomas and Monoclonal Antibodies 66 Applications in the Prenatal Setting 100 Antigen– Reactions 66 Applications in the Transfusion Setting 101 The Zeta Potential 66 Limitations of DNA Analysis 102 Hydration and Surface Tension 67 Other Applications for Molecular Analyses 102 Immune Response to Blood Products and Regulatory Compliance 104 Subsequent 67 SUMMARY 104 Mechanisms of 67 REVIEW QUESTIONS 104 Complement 69 ACKNOWLEDGMENT 105 Components of the Complement System 70 REFERENCES 105 Effects of Complement Activation 72 SUMMARY 73 REVIEW QUESTIONS 73 8 Pretransfusion Testing 107 REFERENCES 73 Pretransfusion Testing 108 The Requisition 108 Request Forms 108 UNIT 3 Patient Identity 109 PRINCIPLES OF TESTING 75 The Patient Sample 109 Type and Screen 110 6 Red Cell Antibody Detection and Methodologies and Antigen/Antibody Reaction Gradings 110 Identification 75 The ABO Blood Group 111 Red Cell Antigen and Antibody Reactions 75 The Rh Type 111 Selection of Method for Detection of Antibodies 76 Antibody Detection (Antibody Screen) 111 Principles of the Antiglobulin Test 76 Blood Selection Guidelines 112 The Indirect Antiglobulin Test 76 The Crossmatch 113 Antibody Screening 77 The Immediate-spin Crossmatch 113 Selection of Screening Cells 77 The Indirect Antiglobulin Test Crossmatch 113 Role of Antibody Screening Tests in Special Considerations for Infants Younger Compatibility Testing 77 Than 4 Months of Age 114 Selection of Test Method 78 ABO/Rh 114 Selection of Incubation Phase 79 Antibody Screen 115 Selection of Antiglobulin Sera 79 Crossmatch 115 Antibody Identification 79 The Electronic “Computer” Crossmatch 115 Steps in Antibody Detection and Identification— Blood Requests for Surgery 115 Preanalytic Phase 79 Exceptional Protocols 116 Steps in Antibody Detection and Identification— Massive Transfusion 116 Analytic Phase 81 Emergency Requests for Blood 116 Direct Antiglobulin Test Negative Samples 81 Autoimmune Hemolytic Anemia 116 Steps in Antibody Identification—Postanalytic Phase 83 Issuing Blood 116 Serologic Testing for Provision of Blood Products 85 SUMMARY 117 Lean Approach 86 REVIEW QUESTIONS 117 Diagnostic Testing for Autoimmune Disease 87 REFERENCES 118 Autoimmune Hemolytic Anemia—Direct Antiglobulin Test Negative 87 82043_fm.qxd 11/13/09 4:34 PM Page xi

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UNIT 4 SUMMARY 147 REVIEW QUESTIONS 148 ED LOOD ELL ROUPS AND R B C G HLA 119 ADDITIONAL READINGS 148 PROCEDURAL APPENDIX 149 9 The ABO Blood Group System 119 Inheritance 120 11 Other Blood Group Systems 150 Bombay 121 Classification and Nomenclature 150 Inheritance of the Bombay Phenotype Carrier Molecule Type 153 (Oh or ABHnull) 122 Carrier Molecule Function 153 Antigen Development 123 Phenotypes 154 Antibodies of the ABO System 124 MNS Blood Group System (ISBT 002) 154 Anti-A 125 Biochemistry and Genetics 154 Anti-A1 125 Antigens of the MNS System 155 Anti-B 125 Glycophorin Deficiencies 157 Anti-A,B 126 Hybrid Glycophorins 157 Anti-H 126 Antibodies in the MNS System 157 Forward Grouping 126 P Blood Group System (ISBT 003), Microplate and Gel Testing 126 Blood Group System (ISBT 028), and Reverse Grouping 127 Globoside Blood Group Collection 158 Molecular Testing 127 History 158 ABH System in Disease 127 Phenotypes of the P and Globoside Blood Group 127 System/Collection 158 Subgroups of A 128 Biochemistry and Genetics 159 Subgroups of B 129 P Antibodies 160 Discrepancies in ABO Grouping 129 Lutheran Blood Group System (ISBT 005) 161 Technical Errors 129 History of Lutheran 161 Weak or Missing Antibodies 130 Lutheran Biochemistry and Genetics 161 Weak or Absent Antigens 131 Lutheran Antigens 161 Unexpected Cold-reactive Autoantibodies 131 Lutheran Antibodies 162 Unexpected Cold-reactive Antibodies 132 Kell Blood Group System (ISBT 006) 162 Rouleaux 132 History 162 Miscellaneous 133 Biochemistry and Genetics 163 SUMMARY 134 The Kell System Antigens 163 REVIEW QUESTIONS 134 Kell System Antibodies 165 REFERENCES 135 Lewis Blood Group System (ISBT 007) 165 PROCEDURAL APPENDIX I 136 History 165 PROCEDURAL APPENDIX II 137 Lewis Antigens 165 PROCEDURAL APPENDIX III 138 Biochemistry and Genetics 166 Lewis Antibodies 167 10 The 139 Lewis Antigens and Antibodies in 168 Genes 139 Clinical Significance of Lewis System Antibodies 168 Nomenclature 140 Duffy Blood Group System (ISBT 008) 169 Most Probable Genotype 141 History 169 D Antigen 142 Biochemistry and Genetics 169 Weak D 142 The High-incidence Antigens: Fy3, Fy4, Fy5, and Fy6 and Partial D 142 their Antibodies 169 Clinical Significance of Weak D and Partial D 142 Duffy Antigens and Malaria 170 C and c Antigens 143 Duffy Antibodies 170 Altered C and c Antigens 143 Kidd Blood Group System (ISBT 009) 170 E and e Antigens 143 Biochemistry and Genetics 170 Altered E and e Antigens 143 Kidd Antigens 170 Deleted or Partially Deleted Phenotypes 143 Kidd Antibodies 170 The G Antigen 144 Diego Blood Group System (ISBT 010) 171 Compound Antigens 144 Biochemistry and Genetics 171 Yt Blood Group System (ISBT 011) 172 Rhnull 144 Rh Antibodies 144 GPI-linked Molecules and PHN 173 Xg Blood Group System (ISBT 012) 173 Rh Immune Globulin 145 a Rh Molecular Testing 145 Xg 173 Rh Serologic Reagents 145 CD99 173 Slide Testing 146 Scianna Blood Group System (ISBT 013) 174 Tube Testing 146 Scianna Antigens 174 Automated and Microplate Testing 146 Scianna Antibodies 174 Gel Testing 146 Dombrock Blood Group System (ISBT 014) 174 Technical Considerations for Rh Typing 146 Dombrock Antigens 174 Rh Typing Discrepancies 147 Dombrock Antibodies 174 82043_fm.qxd 11/13/09 4:34 PM Page xii

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Colton Blood Group System (ISBT 015) 174 Crossmatch 207 Colton Antibodies 175 Comparison of Antibody Testing Techniques 207 Chido/Rogers Blood Group System (ISBT 017) 175 Clinical Applications 208 Chido/Rogers Antigens 175 Solid 208 Chido/Rogers Biochemistry and Genetics 175 Hematopoietic Stem Cell Transplantation 209 Ch/Rg Antibodies 175 Platelets Transfusion Therapy 210 Kx Blood Group System (ISBT 019) 175 HLA and Disease Association 211 Biochemistry and Genetics 175 SUMMARY 212 Gerbich Blood Group System (ISBT 020) 175 REVIEW QUESTIONS 212 Biochemistry and Genetics 176 REFERENCES 213 Antibodies 176 Cromer Blood Group System (ISBT 021) 176 Biochemistry and Genetics 176 UNIT 5 KNOPS Blood Group System (ISBT 022) 177 TRANSFUSION PRACTICES 217 Biochemistry and Genetics 177 Antibodies 177 13 Transfusion Therapy and the Role of the Indian Blood Group System (ISBT 023) 177 Ok Blood Group System (ISBT 024) 177 Medical Director in Blood Banking 217 RAPH Blood Group System (ISBT 025) 177 Whole Blood 218 JMH Blood Group System (ISBT 026) 178 Red Blood Cells 218 I Blood Group System (ISBT 027) Indications 218 and Ii Blood Group Collection 178 Dose and Administration 220 History of the I System/Ii Collection 178 Modifications of Red Cell Components 221 Biochemistry and Genetics 178 Platelets 222 Development of I and i Antigens 178 Indications 222 Antibodies in the Ii System 178 Contraindications 222 Reagents and Testing Methods 178 Dose and Administration 223 I and Disease 179 Assessing Response to Transfusion 223 GIL Blood Group System (ISBT 029) 179 Refractoriness 223 RH-Associated (ISBT 30) 180 Platelet Selection for Refractory Patients 223 Blood Group Collections 180 Platelet Modifications 224 Cost 180 Granulocyte Transfusions 224 Er 180 Indications 224 Vel 180 Dosage and Administration 224 Series of Low- and High-Incidence Antigens 181 Plasma 225 Low-incidence Antigens 181 Indications 225 High-incidence Antigens 181 Contraindications 225 SUMMARY 182 Available Plasma Products 225 REVIEW QUESTIONS 183 Dose and Administration 225 REFERENCES 183 Cryoprecipitated Antihemophilic Factor ADDITIONAL READINGS 187 (Cryoprecipitate) 226 Indications 226 12 Human Leukocyte Antigens 188 Contraindications 226 Genomic Organization of the HLA System 189 Dose and Administration 226 Structures and Functions of MHC Molecules 189 Clotting Factor Concentrates 226 HLA Class I Molecules 189 Recombinant Factor VIIa Concentrate 226 HLA Class II Molecules 191 Factors VIII and IX Concentrates 227 Expression and Tissue Distribution 192 Other Plasma Components 227 Nomenclature of HLA 192 Massive Transfusion 228 Inheritance of HLA 194 Pediatric Transfusion 228 Linkage Disequilibrium 195 Whole Blood, Reconstituted Whole Blood, or Modified Clinical Histocompatibility Testing 195 Whole Blood 228 Serologic Methodologies 196 Red Blood Cells 228 Complement-dependent Microcytotoxicity 196 Platelets 229 The Mixed Lymphocyte Culture Test 198 Plasma 229 DNA Methodologies 198 Cryoprecipitate 229 Quality Control of DNA Laboratory 200 Granulocytes 229 DNA-based Typing 200 Alternatives to Allogeneic Transfusion 229 Luminex Technology 202 Preoperative Autologous Donation 239 PCR-SBT 202 Intraoperative Blood Salvage (Cell Salvage) 230 Screening and Characterization of HLA Antibody 205 Postoperative Blood Salvage 230 Relevance of Antibody in Solid Organ Acute Normovolemic Hemodilution 230 Transplantation 205 SUMMARY 230 Relevance of Antibody in REVIEW QUESTIONS 231 Therapy 205 REFERENCES 231 Techniques for Antibody Testing 206 82043_fm.qxd 11/13/09 4:34 PM Page xiii

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UNIT 6 Bacterial 273 Syphilis 273 CLINICAL CONDITIONS ASSOCIATED WITH Lyme Disease (Borreliosis) 274 IMMUNOHEMATOLOGY 233 Yersinia Enterocolitica 275 Parasitic Infections 276 14 Adverse Effects of Transfusion 233 Malaria 276 Chagas Disease 277 Investigation of Adverse Reactions 234 Toxoplasmosis 277 Transfusion-Related Acute Lung Injury 235 Babesiosis 278 Case Study 1 236 Leishmaniasis 279 Discussion 236 SUMMARY 279 Etiology 236 REVIEW QUESTIONS 279 Transfusion-Associated Circulatory Overload 237 REFERENCES 280 Case Study 2 238 ADDITIONAL READINGS 281 Discussion 238 Treatment and Prevention 238 16 Hemolytic Disease of the Fetus Antigen–Antibody Reactions 238 Intravascular and Extravascular 238 and Newborn 283 Etiology 239 Maternal Alloimmunization 284 Treatment and Prevention 239 Pathophysiology of HDFN 284 Case Study 3 240 Assessing the Risk for Hemolytic Disease 285 Discussion 240 Prenatal Evaluation 285 Delayed Extravascular Hemolysis 241 Performing Antibody Titration Studies 286 Case Study 4 241 Repeat Antibody Screening 287 Discussion 241 Amniocentesis 287 Etiology 242 Nonserologic Method of Assessing Fetal Risk 288 Transfusion-Related Bacterial 242 Obtaining a Fetal Blood Specimen 288 Case Study 5 242 Predicting Fetal Antigens 288 Discussion 243 Intrauterine Transfusions 290 Etiology 243 Red Blood Cell Selection and Preparation 290 Treatment and Prevention 243 Cord Blood Testing 290 Allergic and Anaphylactic Reactions 243 Compatibility Testing for Transfusion After Birth 291 Case Study 6 243 Unit Selection 292 Discussion 243 Serologic Testing 292 Treatment and Prevention 244 Prevention of HDNF Due to Anti-D 292 Febrile Nonhemolytic Transfusion Reaction 244 Serologic Testing 293 Delayed Transfusion Reactions 245 Quantifying Fetal-Maternal Hemorrhage 293 Transfusion-Associated Graft-Versus-Host Disease 245 Previously Sensitized Women 294 Case Study 7 245 Administer RHIG Within 72 Hours 294 Discussion 245 Neonatal Thrombocytopenic Purpura 294 Posttransfusion Purpura 245 SUMMARY 294 Alloimmunization to HLA Antigens 246 REVIEW QUESTIONS 294 Case Study 8 246 REFERENCES 295 Discussion 246 Miscellaneous Reactions 246 17 Autoimmune Hemolytic Anemias and Out-of-type Plasma Reactions 246 Drug-Induced Immune Hemolytic Anemia 297 Hypothermia 247 Immune Hemolysis 298 Potassium Abnormalities 247 Clinical and Laboratory Indicators of Hemolysis 298 Transfusion-related Immunomodulation 247 Classification of Autoimmune Hemolytic Anemias 299 Transfusion-associated Iron Overload 247 Serologic Tests to Investigate Autoimmune 247 Hemolytic Anemia 299 Storage Lesion 247 Warm Autoimmune Hemolytic Anemia 301 Morbidity and Mortality Associated with Serologic Characteristics 301 Transfusion 248 Serologic Problems 301 Records of Adverse Transfusion Events 248 Autologous Adsorption 301 REVIEW QUESTIONS 249 Allogeneic Adsorption 302 REFERENCES 250 Specificity of Autoantibody 302 Transfusion of Patients with Warm-reactive 15 Transfusion-Transmitted Diseases 252 Autoantibodies 302 Viral Infections 252 Cold Agglutinin Syndrome 303 Hepatitis Viruses 253 Serologic Characteristics 303 Retroviruses 263 Serologic Problems 304 Herpesviruses 269 Detection of Alloantibodies in the Presence of Cold-reactive Other Virus Transmitted by Blood 272 Autoantibodies 304 Prions 273 Specificity of Autoantibody 304 82043_fm.qxd 11/13/09 4:34 PM Page xiv

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Mixed-Type AIHA 304 The Food and Drug Administration 344 Serologic Characteristics 305 History 344 Specificity of Autoantibody 305 Objective 344 Transfusion in Mixed-type AIHA 305 Blood Products Advisory Committee 344 Paroxysmal Cold Hemoglobinuria 305 Regulations 344 Serologic Characteristics 305 Inspection 345 Specificity of Autoantibody 305 Enforcement 345 Transfusion in PCH 305 Centers for Medicare and Medicaid Services 346 Drug-Induced Immune Hemolytic Anemia 305 The Joint Commission 349 Serologic Classification 307 Objectives 349 Management of DIIHA 311 Inspection Process 349 Laboratory Investigation of DIIHA 312 Compliance Issues for Services 349 Clinical and Serologic Features of DIIHA Due to Cefotetan, Enforcement 349 Ceftriaxone, and Piperacillin 314 College of American Pathologists 349 SUMMARY 315 Objectives 349 REVIEW QUESTIONS 315 Compliance Issues 350 REFERENCES 316 Proficiency Test Samples 350 Other Agencies 350 International Organization for Standardization 350 UNIT 7 Nuclear Regulatory Commission 351 QUALITY ASSURANCE AND REGULATORY ISSUES 319 Department of Transportation 351 Environmental Protection Agency 351 Occupational Safety and Health Administration 351 18 Quality Assurance and Safety in SUMMARY 351 Immunohematology 319 REVIEW QUESTIONS 352 Quality Assurance 320 REFERENCES 352 Quality Assurance Department 321 ADDITIONAL READINGS 352 Personnel 321 Standard Operating Procedures 322 Documentation and Records 323 UNIT 8 Nonconformance 325 ADDITIONAL TOPICS OF INTEREST 354 Peer Review 326 Quality Assurance Audits 326 Inspections 327 20 Information Technology 354 Supplier Qualification 327 Regulatory Requirements for Computer Systems 355 Facilities, Equipment, and Process Activities 327 Terminolgoy 355 Computers 329 Validation 355 Label Control 330 The Validation Protocol 356 Lot Release 330 Implementing Computerization 356 Problem Solving 330 Requirements 356 Summary 332 Prioritization of Information Technology Projects 357 Biosafety in Blood Establishments 333 Information Technology Procedures 358 Regulatory Agencies 333 SUMMARY 358 Classification of Work Activity 333 REVIEW QUESTIONS 358 Standard Operating Procedures and Training 333 REFERENCES 359 Universal Precautions 334 Personal Protective Equipment 334 21 Process Management 360 Safety Practices 335 Understanding Processes 360 Needle Precautions 336 Process Control Elements 361 Storage 336 Standard Operating Procedures 361 Transportation 337 Training 361 Basic Safety Precautions 337 Instrument and Equipment Monitors 361 Injuries and Exposures 337 Review 361 Management of Exposure to HIV 338 Quality Control 362 Waste Management 338 Internal Self-assessment 362 Radiation 339 Statistical Process Control 362 SUMMARY 339 Data Collection 362 REVIEW QUESTIONS 339 Total Quality Tools 363 REFERENCES 340 Pareto Chart 363 ADDITIONAL READINGS 340 Flowchart 363 Histograms 364 19 Regulations and Standards 342 Scatter Diagrams 365 AABB 342 Run Charts 366 Objectives 342 Control Charts 366 AABB Quality Plan 343 Cause-and-Effect Diagrams 367 82043_fm.qxd 11/13/09 4:34 PM Page xv

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Supplier Qualification 369 Overview of Project Management Body of Knowledge: Supplier Impact 369 Processes and Knowledge Areas 375 Supplier Qualification 369 Processes: The Way a Project Flows 375 The Process of Supplier Qualification 369 Knowledge Areas: The Why-To-Do Project Change Control 370 Management 376 Six Sigma and Lean 370 So You Want to Implement Project Management? 378 Six Sigma 370 Key Concepts to Implementing Project Management 378 Six Sigma Methodology 370 What Is Program and Portfolio Management? 379 Roles in Six Sigma 371 SUMMARY: VALUE AND PITFALLS OF Tools of Six Sigma 371 PROJECT MANAGEMENT 380 Lean Principles 371 REVIEW QUESTIONS 380 SUMMARY 372 REFERENCES 381 REVIEW QUESTIONS 373 REFERENCES 373 Appendix: Answers to Review Questions 382 ADDITIONAL READINGS 373 Glossary 386 22 Principles of Project Management 374 Index 398 What Is a Project? 374 What Is Project Management and What Is a Project Manager? 374