Essential Guide to Blood Groups

Geoff Daniels , Consultant Clinical Scientist and Head of Diagnostics, IBGRL, Bristol Institute for Transfusion Services, NHS Blood and Transplant, Bristol, UK Imelda Bromilow , Scientific Consultant, Liverpool, UK

Abbreviations x 1 An introduction to blood groups 1 What is a blood group? 1 Blood group antibodies 3 Clinical importance of blood groups 3 Biological importance of blood groups 3 Blood group systems 4 Blood group terminology and classification 4 2 Techniques used in blood grouping 8 Factors affecting antigen--antibody reactions 8 Temperature 8 Time and ionic strength 9 pH 9 Antigen density 9 Stages of haemagglutination reactions 10 Direct agglutination 11 Indirect agglutination 12 Enzyme techniques 12 Antiglobulin tests 14 Elution techniques 18 Automation of test procedures 19 Flow cytometry 19 Molecular blood group genotyping 21 3 The ABO blood groups 22 Introduction 22 ABO antigens, antibodies, and inheritance 22 A1 and A2 23 Antigen, phenotype, and gene frequencies 24 ABO antibodies 25 Importance of the ABO system to transfusion and transplantation medicine 26 Biochemical nature of the ABO antigens 27 Biosynthesis of the ABO antigens and ABO molecular genetics 28 H, the precursor of A and B 30 ABH secretion 31 H-deficient red cells 32 Further complexities 32 Acquired changes 33 Associations with disease and functional aspects 34 4 The Rh blood group system 35 Introduction -- Rh, not rhesus 35 Haplotypes, genotypes, and phenotypes 36 Biochemistry and molecular genetics 37 D antigen (RH1) 40 Molecular basis of the D polymorphism 40 D variants 41 Clinical significance of anti-D 42 D testing 44 C, c, E, and e antigens (RH2, RH4, RH3, RH5) 44 Clinical significance of CcEe antibodies 45 Molecular basis of the C/c and E/e polymorphisms 45 Other Rh antigens 45 Compound antigens: ce, Ce, CE, cE (RH6, RH7, RH22, RH27), and G (RH12) 46 Cw, Cx, and MAR (RH8, RH9, RH51) 46 VS and V (RH20, RH10) 46 Rh-deficient phenotypes -- Rhnull and Rhmod 47 Putative function of the Rh proteins and RhAG 47 5 Other blood groups 49 The Kell system 49 The Kell glycoprotein and the KEL gene 49 Kell system antigens 50 Kell system antibodies 51 Ko phenotype 51 McLeod syndrome, McLeod phenotype, and Kx (XK1) antigen 52 The Duffy system 52 Fya (FY1) and Fyb (FY2) 52 Anti-Fya and -Fyb 53 Fy3 and Fy5 53 The Duffy-glycoprotein, a receptor for chemokines 53 Duffy and malaria 54 The Kidd system 54 Jka (JK1) and Jkb (JK2); anti-Jka and -Jkb 54 Jk(a-b-) and Jk3 55 The Kidd-glycoprotein is a urea transporter 55 The MNS system 56 M (MNS1) and N (MNS2); anti-M and -N 56 S (MNS3) and s (MNS4); anti-S and -s 56 S- s- U- phenotype and anti-U 57 Other MNS antigens and antibodies 57 The Diego system 57 Band 3, the red cell anion exchanger 57 Dia (DI1) and Dib (DI2); anti-Dia and -Dib 58 Wra (DI3) and Wrb (DI4); anti-Wra and -Wrb 58 Other Diego-system antigens 59 The Lewis System 59 Some other blood group systems 61 P1PK 61 Lutheran 61 Yt 61 Xg 61 Scianna 61 Dombrock 62 Colton 62 Landsteiner--Wiener (LW) 62 Chido/Rodgers 62 Gerbich 62 Cromer 63 Knops 63 Indian 63 I 63 JR and Lan 64 Vel 64 Antigens that do not belong to a blood group system 64 6 Clinical significance of blood group antibodies 65 Antibody production and structure 66 Factors affecting the clinical significance of antibodies 69 Antibody specificity 69 Haemolytic transfusion reactions (HTR) 71 Intravascular red cell destruction 72 Extravascular red cell destruction 72 Haemolytic disease of the fetus and newborn (HDFN) 73 Crossmatching for infants under 4 months old 75 Autoantibodies 77 Tests to assess the potential significance of an antibody 77 Decision-making for transfusion 78 7 Blood grouping from DNA 81 Fetal blood grouping 81 Blood group typing of patients and donors 82 Next generation sequencing 84 The future of blood group serology 84 8 Quality assurance in immunohaematology 85 Achieving total quality 85 Frequency and specificity of control material 86 Quality requirements for safe transfusion practice 88 Checklist of critical control points 89 Laboratory errors, root cause analysis (RCA), and corrective and preventive action (CAPA) 89 9 Trouble-shooting and problem-solving in the reference laboratory 92 ABO grouping 92 Rh grouping 94 Problems in antibody screening, identification, and crossmatching 95 10 Frequently asked questions 102 What is the difference between sensitivity and specificity and how can these be determined? 102 Why is anti-A,B no longer obligatory in ABO typing? 102 Why are two anti-D reagents often recommended for RhD typing? 103 What is the importance of detecting D variant (weak D and partial D) phenotypes? 103 How do I control the results for antiglobulin testing? 103 Why should RhD positive women be tested more than once during pregnancy? 104 How often should transfusion recipients be tested for the presence of antibodies? 104 How can passive anti-D be differentiated from anti-D due to alloimmunisation? 104 Why do we need to perform antibody screening? Isn't a crossmatch by IAT at 37degreeC enough to detect incompatible blood? 105 What is the incidence of alloimmunisation post-transfusion? 105 How do I determine and identify antibodies present in a sample? 105 What is a compound antibody? 105 How can the incidence of compatible donors for a recipient with multiple antibodies be calculated? 106 Why can't the droppers in bottles of reagents be used instead of a volumetric pipette? 106 What cells should be used when performing an antibody titration? 107 How are the results of titrations reported? 107 What is a Major Obstetric Haemorrhage? 107 What is 'Massive Transfusion'? 107 When group-specific blood is in short supply, how do I select the 'next best' for transfusion? 108 How are high-titre haemagglutinins classified? 108 What is an 'immediate spin' crossmatch? 108 What is an 'electronic crossmatch'? 108 Which patients are not eligible for electronic issue of blood? 108 What is 'bed-side' testing? 109 What are signs and symptoms of a suspected transfusion reaction? 109 What action should be taken in the event of a suspected transfusion reaction? 109 In haemovigilance, how should 'near-miss' events be characterised? 109 Recommended reading and web sites 111 Index 113