Blood Group Terminology and other Blood Groups PDF

9/23/2024 Blood Group Terminology and other Blood Groups C...

9/23/2024 Blood Group Terminology and other Blood Groups CHAPTER 8 Preamble PowerPoints are a general overview and are provided to help students take notes over the video lecture ONLY. PowerPoints DO NOT cover the details needed for the Unit exam Each student is responsible for READING the TEXTBOOK for details to answer the UNIT OBJECTIVES Unit Objectives are your study guide (not this PowerPoint) Test questions cover the details of UNIT OBJECTIVES found only in your Textbook! 1  9/23/2024 Terminology A blood group system is a group of antigens produced by alleles at a single gene locus or at loci so closely linked that crossing over does not occur or is very rare Most are codominant Some genes code for complex structures that carry more than one antigen (glycophorin B structure carries S or s antigen also carries N and U) RBC with null phenotypes can be helpful when evaluating antibodies to unknown high frequency antigens Terminology Regulator or modifying genes alter antigen expression Not located at same locus as blood group gene Genes are underlined or italicized, and allele is subscript Antigens are not underlined or italicized and have common names Antibodies are described by “anti” preceding 2  9/23/2024 Correct Blood Group Terminology Gene Antigen Antigen + Antigen Antibody System - K K K+ K- Anti-K Kell or KEL Jka Jka Jk(a+) Jk(a-) Anti-Jka Kidd or JK P1k P1 P1+ P1- Anti-P1 P Lu4 Lu4 Lu:4 Lu:-4 Anti- Lu4 Lutheran or LU Lewis (007)System Only blood group system that is not manufactured by the red blood cell Antigens are manufactured by tissue cells and secreted into body fluids Referred to as a system not a group Antigens are adsorbed onto the red cell Dependent on inheritance of Lewis genes and secretor genes Genetic interaction between Lewis genes and ABO genes 3  9/23/2024 Lewis - Inheritance Similar to ABO genes Lewis (Le) gene does not code for production of Lewis antigen Produces an enzyme glycosyltransferase (L-fucosyltransferase) Adds L-fucose to basic precursor substance Lewis - Inheritance Located on Chromosome 19 close to Se and H genes 90% of whites possess the Le gene Le gene codes for L-fucosyltransferase, which adds L-fucose to the type 1 chain Inheritance of Le gene acts in competition with ABO genes Transfer reaction can occur only in type 1 chain, not type 2, because of precursor substances 4  9/23/2024 The Lewis (a+b-) Phenotype: Nonsecretors Lea substance is secreted regardless of the secretor status Secretor refers only to presence of ABH antigen substances in body fluids (Se and se) A nonsecretor (sese) will secrete Lea into body fluids Phenotype Le (a+b-) are nonsecretors of ABH substances The Lewis (a-b+) Phenotype: Secretors Interaction between Sese, ABO, Hh and Lewis genes are intimately associated in the formation of the Leb antigen Lea and Leb are not alleles Leb are secretors Le gene is needed for expression of Lea substance and Le and Se genes are needed to form Leb substance 5  9/23/2024 The Lewis (a-b+) Phenotype: Secretors Leb antigen represents the product of genetic interaction between Le(FUT3) and Se(FUT2) genes Se gene codes for enzyme which adds L-fucose to type 1 precursor and forms type 1 H Leb antigen is formed when second L-fucose is added to number 4 carbon of the subterminal N- acetyl-D-glucosamine of type 1 H The Lewis (a-b+) Phenotype: Secretors All Le(a-b+) are ABH secretors and have both Lea soluble and Leb soluble antigens in secretions Only Leb adsorbs onto the red cell Phenotype as Le(a-b+) In Lea, antigens are formed in secretions of sese Most common phenotype in blacks and whites is Le(a- b+) 6  9/23/2024 The Lewis (a-b-) Phenotype – Secretors or Nonsecretors The lele genotype is more common among blacks than in whites and will phenotype as Le(a-b-) Not caused by the absence of the Lewis gene, but rather by specific point mutations in the Le gene. Lewis antigen is absent only on the red cells but present in secretions of Le(a-b-) secretors Substances Present in Secretions- See Chart Gene Inherited Substances in Red cell Secretions phenotypes Le, Se, A/B/H Lea, Leb,A, B, H A,B,H, Le(a-b+) lele, Se, A/B/H A, B, H A,B,H, Le(a-b-) Le, sese, A/B/H Lea A,B,H, Le(a+b-) lele, sese, A/B/H --- A,B,H, Le(a-b-) Le, sese, hh, A/B Lea Oh , Le(a+b-) Le, Se, hh, A/B Lea, Leb, A, B, H A, B, Le(a-b+) 7  9/23/2024 Adult Phenotype Frequency in %- See chart Phenotype Whites Blacks Le(a+b-) 22 23 Le(a-b+) 72 55 Le(a-b-) 6 22 Facts about Lewis Antigens Lewis antigens become weaker during pregnancy Lewis antigens are poorly expressed at birth Lewis antigens do not demonstrate dosage in serologic reactions 8  9/23/2024 Lewis Antibodies Lewis antibodies are generally IgM (naturally occurring) Capable of binding complement Enhanced by enzymes Lewis substances in secretions can neutralize Lewis antibodies Lewis antibodies are frequently encountered in pregnant women. Type as Le(a-b-) Not considered significant in transfusion medicine Lewis Antibodies Some cases of HTR by anti-Lea and RBC destruction by anti-Leb Considered insignificant Antibodies can be neutralized by Lewis substances in plasma decreasing quantity Generally IgM – do not cross placenta, do not cause HDN, also Lewis antigens not fully developed at birth Lewis antigens from donor RBC’s can dissociate from the red cells and be neutralized by recipient’s antibodies 9  9/23/2024 Anti-Lea Most commonly encountered – 20% of those Le(a-b-) IgM with some IgG components or may be entirely IgG IgM can bind complement causing in vivo and in vitro hemolysis If a reaction at AHG phase – DO NOT IGNORE Anti-Leb Not as common or as strong IgM – does not fix complement as well as Anti-Lea Produced by Le(a-b-) people 10  9/23/2024 Anti-Lex Produced by phenotype Le(a-b-) Agglutinates all Le(a+b-) and Le(a-b+) red cells Agglutinates 90% of white cord blood Combined antibody Serologic Characteristics Anti- Lea and Anti-Leb Anti- Lea Anti- Leb Saline – 4-220 C Most Most Albumin - 370 C Few Few AHG Many Few Enzymes Many Few Hemolysis Some Occasional 11  9/23/2024 The MNSs Blood Group System Landsteiner looking for new antigens Immunized rabbits and recovered antibodies Found two: anti-M and anti-N 20 years later Walsh discovered S and s MN are alleles of each other and Ss are alleles of each other Two loci system – Close together Frequency of MNSs Phenotypes Phenotype Whites Blacks M+N- 28 26 M+N+ 50 44 M-N+ 22 30 S+s- 11 3 S+s+ 44 28 S-s+ 45 69 S-s-U- 0 1 12  9/23/2024 MNSs U Antigens Weiner discovered high incident antigen U (Universal) All U- RBC’s were also S-s- Placed U in the MNSs system 40 antigens are included into MNSs system Many are low frequency MNSsU Antigens Antigens exhibit dosage Homozygous MM carry double dose of M antigen and react more strongly with anti-M cells than heterozygous MN Antigens develop by 9 weeks gestation Useful in paternity exclusion Destroyed or removed by enzymes Ficin, papain, bromelain, trypsin, & pronase 13  9/23/2024 MNSs U Antigens Ss Antigens Rhnull red cells have reduced expression of Ss Ss antigens are degraded by enzymes Anti- M Naturally occurring Cold-reactive (React below body temperature) - nonhemolytic Saline agglutinin Thought of as IgM, but 50-80% are IgG Do not bind complement – Regardless of immunoglobulin class 14  9/23/2024 Anti-M Dosage M+N- (MM genotype) react with anti-M more strongly M+N+ (MN genotype) react with anti-M less strongly Weak anti-M may not react with M+N+ cells at all Antibody panel difficult Anti-M Antibody reactivity enhanced by increasing serum to red cell ratio Increasing incubation time Decreasing incubation temperature Adding potentiating medium Can be pH dependent (pH 6.5) 15  9/23/2024 Anti-N Rarer than anti-M Similar to anti-M Cold reactive IgM or IgG Saline agglutinin Does not bind complement Demonstrates dosage Anti-N found in renal patients (regardless of MN type) who are dialyzed on equipment cleaned with formaldehyde Anti S and Anti-s Most are IgG Reactive at 370C and Coombs Rare Bind complement Implicated with severe HTR and HDN 11% of whites and 3% of blacks are s- : difficult to find blood for those with anti-s 16  9/23/2024 Kahoot Time - Get your phones ready! https://create.kahoot.it/details/dd9b6a26-96b2-4b35-8052-6d1fdb2d9fcf BREAK TIME 17  9/23/2024 P and Pk Blood Antigens P1 found in room temperature testing P1 strong individuals P1 weak individuals P1 antigens deteriorate rapidly during storage Similar to A1 and A2 antigens P and Pk Blood Antigens P occurs universally on RBC’s, WBC’s, and tissue cells, sometimes in secretors Pk is rare – lack the P antigen Fetus have antigen at 12 weeks, but weakens as fetus develops – poorly expressed at birth Takes up to 7 years to fully express 18  9/23/2024 Anti P1 Naturally occurring IgM in sera of P2 individuals Usually weak, cold-reactive, saline agglutinin Detected at room temp or bind complement at Coombs phase Use prewarmed test methods Anti P1 Provide units that are crossmatch compatible at 370C and Coombs phase regardless of P1 status Does not cause a rise in titer Rare examples may react at 370C causing both HTR and delayed transfusion reaction HDN is not associated with anti-P1 19  9/23/2024 Interesting facts about anti -P1 Anti-P1 like antigens have been found in red cells, plasma, and droppings of pigeons and turtledoves. P2 people who are bird handlers can develop a strong, clinically significant anti-P1 Ii Antigens I and i are both high frequency antigens Wide range of strengths At birth – cells are rich in i with I almost undetectable During first 18 months of life i decreases until adult proportions are I are reached Adults red cells are rich in I with trace amounts of i. 20  9/23/2024 Anti-I Stimulated by microorganisms – Mycoplasma pneumoniae Common autoantibody Can be benign or pathogenic Strong reactions with adult cells and weak reactions with cord blood Incubating in cold enhances anti-I Prewarm inhibits reaction Anti-I Albumin and enzymes enhance reactions Complicate transfusions Exists as alloantibody IgM or IgG in patients who are i Usually, no problem if transfused at 370C Not associated with HDN 21  9/23/2024 Anti-I Can mask clinically significant underlying alloantibodies Identify the antibody and confirm it is an auto-anti-I Prove there are no other significant alloantibodies present Eliminate the autoantibody by prewarmed techniques Kell System High and low frequency antigens Found only on RBC’s K antigen detected as early as 7 – 10 weeks of gestation (k at 7 weeks) Shows dosage Not destroyed by ficin or papain, but are destroyed by trypsin 22  9/23/2024 Kell System K and k antigens So immunogenic – 2nd only to D K-k+ = 91% whites and 96% black K- people transfused with one unit of K+ blood, 10% will make anti-K If anti-K develops compatible units are easy to find k antibodies are rare – 2 in 1000 Kell System Kpa, Kpb, Kpc, and VLAN antigens Low frequency mutations Suppresses expression of other Kell genes Jsa and Jsb antigens high frequency Jsb Jsa low frequency: found in 20% of blacks and 0.1% of whites Linked to Kell system when K0 cells are Js(a-b-) 23  9/23/2024 Anti-K Clinically significant – severe HTR and HDN Anti-K is most common antibody outside of ABO and Rh antibodies IgG Reactive in Coombs 20% bind complement, seldom lytic Exposure through transfusion or pregnancy – persists for years Anti-K Naturally occurring, IgM anti-K is rare – associated with bacterial infections Most reliable test is IAT Shows dosage effect Implicated in severe HTR and extravascular destruction Associated with severe HDN 24  9/23/2024 Anti-K Antibodies are rare, so few are exposed to antigen Detected through incompatible crossmatches or cases of HDN K0 is null phenotype – silent Kell allele Inherit two recessive K0 genes Express no Kell antigens Make antibodies to all Kell antigens Very rare Kx McLeod phenotype – rare Kx made by a gene on X chromosome Missing Kell antigens Found only in males (X linked) Chronic granulomatous Disease Acanthrocytes WBC’s are not phagocytic No H2O2 production in WBC 25  9/23/2024 Duffy Blood Group System Named for Mr. Duffy – multiple transfused hemophiliac Connection between Duffy System and Malaria For malaria to invade blood the RBC it needs Fya or Fyb 68% of blacks are Fya- Fyb- Duffy System Phenotype White % Black % Chinese % Fy (a+b-) 17 9 90.8 Fy(a+b+) 49 1 8.9 Fy(a-b+) 34 22 0.3 Fy(a-b-) Rare 68 0 26  9/23/2024 Duffy Antigens Do not store well – even frozen Elute from RBC’s Leads to inhibitory substances in supernatant fluid that can weaken reactivity of anti-Fya or Fyb Do not elute in approved blood bank anticoagulants Destroyed by ficin, papain Duffy Antibodies Moderate immunogens Anti-Fya occurs 3 times less frequently and anti K Anti-Fyb is 20 less common than Fya Usually in combination with other antibodies IgG 27  9/23/2024 Duffy Antibodies React best in Coombs Does not usually bind complement Destroyed by enzymes May are may not show dosage Associate with HTR – seldom severe Associated with delayed HTR Implicated with HDN Kidd Blood Group System Simplest and most straightforward Antigens are Jka and Jkb Jk3 on all RBC’s who are either Jka or Jkb positive Not very immunogenic Well developed at birth Not altered by enzymes 28  9/23/2024 Kidd Antibodies Clinically significant – IgG reacts in Coombs Show dosage – but often weak Found in combination with other antibodies Bind complement Common cause of HTR Often delayed type but severe hemolysis has been noted Implicated in HDN Titer quickly declines – wear warning bracelet of Kidd antibody Lutheran System Antigens Lua and Lub – inherited as codominant genes Questionable immunogenticity Poorly developed at birth Have either very high or very low frequency Does not cause many blood bank problems Shows some dosage 29  9/23/2024 Common Lutheran Phenotypes Phenotypes Whites Blacks Lu (a+b-) 0.15 0.1 Lu (a+b+) 7.5 5.2 Lu (a-b+) 92.35 94.7 Lu (a-b-) Very rare Very rare Anti Lua May be naturally occurring – saline agglutination at room temperature Most reagent cells are Lu(a-) antibody may not be detected until incompatible crossmatch Mixed field agglutination Not destroyed by enzymes Lua not clinically significant 30  9/23/2024 Anti Lub IgG antibody Reactive in Coombs Produced in response to foreign red cell exposures Transfusion Pregnancy Lutheran System Lu null (Lu (a-b-) homozygous or called Lutheran inhibitor (InLu) Suppresses P1, and i as well as Lutheran antigens Lu(a-b-) actually do not have antigens and do not suppress other antigens 31  9/23/2024 Diego System Designated as DI and is composed of 22 antigens with three sets of independent pairs: Dia/Dib, Wra/Wrb and Wu/DISK System named after Venezuelan family during an investigation of HDFN Diego antigens are expressed on RBCs of newborns Most Diego antigens are resistant to enzymes Dia antigen is rare in most populations but is polymorphic in people of Mongoloid ancestry. Dia is found in 54% of South American Indians Dib antigen is more prevalent and found in 99% of the population Diego System Sometimes the Diego antibodies are IgM but usually IgG being reactive at the IAT stages Anti-Dia and Anti-Dib have been associated with HTR’s and HDFN Anti-Wra is a common antibody in donors and patients and is mostly detected at the IAT phase Anti-Wra has been associated with severe HTR 32  9/23/2024 Significant Blood Group Systems Rh (E,e,C,c) systems Kell (K), Duffy(Fy) Kidd(Jk) ABO is most significant (and exception) because IgM antibodies are “naturally occurring” and react in vivo Significant Blood Group Characteristics ANTIGEN Antigen Demonstrates Antigen Characteristics expression Dosage Modification at birth By Enzyme Rh System D Strong No Enz C,c, Strong Yes Enz E,e Strong Yes Enz Kell System K, k, Strong Occ Enz no effect Kpa, Kpb Strong Occ Enz no effect Jsa, Jsb Strong Occ Enz no effect Duffy System Fya Strong Yes Enz Fyb Strong Yes Enz Kidd System Jka Strong Yes Enz Jkb Strong Yes Enz 33  9/23/2024 Significant Blood Group Characteristics ANTIBODY Serology Comp. Immunoglobulin Optimum Characteristics Saline AHG Binding Class Temperature IgM IgG Rh System D Occ Yes No Occ Yes Warm C,c, Occ Yes No Occ Yes Warm E,e Occ Yes No Occ Yes Warm Kell System K/k Occ/No Yes Some/No Occ/Rare Yes Warm Kpa/Kpb No/Rare Yes No No/Rare Yes Warm Jsa/Jsb Rare/No Yes No Rare/No Yes Warm Duffy System Fya Rare Yes Some Rare Yes Warm Fyb Rare Yes Rare Yes Warm Kidd System Jka No Yes Yes No Yes Warm Jkb No Yes Yes No Yes Warm “Insignificant” Blood Group Systems” I I Le L ove M My N N ew H H onda P P relude * Antibodies to these antigens are not implicated in HTR/HDN 34  9/23/2024 Kahoot Time - Get your phones ready! https://create.kahoot.it/details/7e4f00dd-2bda-4bcf-a2ce-ed20afddbc19 Know both Antigen and Antibody Characteristics (See front and back cover) Know which common antibodies for each system: react at room temperature react at 370C react at Coombs phase are clinically significant are clinically insignificant cause HTR and HDN bind complement are enhanced or destroyed by enzymes Classwork - Ag/Ab Worksheets 35  9/23/2024 Postamble READ the TEXTBOOK for the details to answer the UNIT OBJECTIVES. USE THE UNIT OBJECTIVES AS A STUDY GUIDE All test questions come from detailed material found in the TEXTBOOK (Not this PowerPoint) and relate back to the Unit Objectives 36