Other Blood Group Systems (FA2023) PDF

OTHER BLOOD GROUP SYSTEMS CHAPTER 8 1 Recipient Identification & Sample Collection and Processing 2 Blood Transfusion Needed Blood Bank Testing Blood Type and Antibody detection/identification 3 4 Compatibility Blood Selection and compatibility testing Recipient Identification & Transfus...

OTHER BLOOD GROUP SYSTEMS CHAPTER 8 1 Recipient Identification & Sample Collection and Processing 2 Blood Transfusion Needed Blood Bank Testing Blood Type and Antibody detection/identification 3 4 Compatibility Blood Selection and compatibility testing Recipient Identification & Transfusion • • • • • • • • • • Phenotype Phenotype Prevalence in Whites (%) Phenotype Prevalence in Blacks (%) Le(a+b-) 22 23 Le(a-b+) 72 55 Le(a-b-) 6 22 Le(a+b+) Rare Rare Not of erythroid origin, they are passively absorbed onto the RBC membrane Not expressed on cord RBCs (newborns type as Le(a-b-)) Diminished on Maternal RBCs (will type as Le(a-b-)) Found all throughout the body: lymphocytes, platelets, tissues (organs), saliva Resist Enzymes Rarely cause HTRs, never HDFN Lea and Leb are not alleles Lewis system depends on Hh, Se, and Le genes le, h, and se do not produce products If the Le gene is inherited, Lea substance is produced Le, H, and Se genes must all be inherited to convert Lea to Leb Le(a+b+) RBCs are rare, except in Asian populations (10-40%) LEWIS GENES Table 7.12 Lewis Genes and Red Cell Phenotypes Genes present Antigens in secretions Red cell phenotype Le sese H Lea Le(a+b–) Le Se H Lea Leb H Le(a–b+) lele sese H None Le(a–b–) lele Se H H Le(a–b–) Le sese hh Lea Le(a+b–) Le Se hh Lea Le(a+b–) lele sese hh None Le(a–b–) lele Se hh None Le(a–b–) • Inherit only FUT3 (Lewis gene) Le(a+b-) • Inherit both FUT3 and FUT2 (Secretor gene) Le(a-b+) • Lea does not turn into Leb • Le(a-b+) still produes small amounts of Lea, thus antiLea is not made IgM Naturally occurring Produced by Le(a–b–) Pregnant women change to Le(a-b-) and will frequently have Lewis antibodies in serum Not clinically significant = XM Compatible RBC (no antigen testing required) Agglutination can occur at immediate-spin (IS), 37°C, and AHG RBCs treated with Enzymes enhance anti-Leb reactivity and may cause hemolysis Anti-Lea binds complement; may cause hemolysis in vitro, especially with enzyme treated cells Neutralization can confirm the presence or eliminate reactions with Lewis antibody Antigens: Pk, P, P1, PX2, FORS1, NOR • P1PK system: Pk, P1, NOR • GLOB system: P, PX2 • FORS system: FORS1 • • • • • • • • • Table 7.14 P1PK and GLOB Blood Group Systems Antigen and Antibody Characteristics Possible Phenotype Antigen characteristics Alloantibody Characteristics antibodies None Not applicable Red cells express P, P1, and Pk P1 antigens P1 antigen is not well developed at birth Most common phenotype P2 IgM; room temperature; not clinically Lacks P1 antigen but expresses P and Anti-P1 k significant P antigens Variable reactions with adult cells Second most common phenotype P1k Red cells express P1 and Pk antigens Anti-P Clinically significant; associated with spontaneous abortions (rare) Very rare phenotype k k Red cells express only P antigens Anti-P and Anti-P and anti-P1 characteristics P2 Very rare phenotype anti-P1 Anti-PP1Pk Hemolytic; clinically significant; can p Null phenotype of system (Tja) be separated into three Negative for P, P1, and Pk antigens Very rare phenotype specificities Anti-P1 • Found in P2 individuals • IgM; enhanced by enzymes • Non-RBC stimulated = naturally occurring • Not implicated in HDFN, rarely HTRs • Can be neutralized by P1 substance (from hydatid cyst fluid) • Associated with parasitic infections Autoanti-P • Associated with paroxysmal cold hemoglobinuria • IgG (Donath-Landsteiner antibody); a biphasic hemolysin that binds with P1 or P2 cells at low temperatures before the complement is activated at body temperature • May appear in children after viral infection Anti-PP1Pk (aka anti-Tja) • Occurs in individuals with the null phenotype • Binds complement and causes hemolysis in vitro • Clinically significant, potential to cause severe HTRs and HDFN, and spontaneous abortions • IgM and IgG Antigens: I and i I and i antigens are not antithetical antigens They form on the precursor A, B, and H chains of RBCs = primary carriers of ABH antigens on red cells Newborns have i antigen. Increase in i antigen in adults seen in paroxysmal nocturnal hemoglobinuria and thalassemia Adults have I antigen i antigen (linear) converts to I antigen (branched) as a child matures (about 2 years of age) Cold-reacting, IgM, naturally occurring, bind complement Alloanti-I is rare autoanti-I: low-titer, Not clinically significant, common Reactions are avoided by prewarming, and using anti-IgG instead of polyspecific AHG autoanti-I: high-titer, broad thermal amplitude, Cold autoimmune hemolytic anemia Reacts as compound antibody •Often found as an anti-IH, particularly in A1 and AB •Stronger agglutination with RBCs having many H sites (O and A2) Autoanti-I • Mycoplasma pneumoniae • Cold hemagglutinin disease Anti-i • Infectious mononucleosis • Alcoholic cirrhosis • Cold hemagglutinin disease (occasionally) THE MNS SYSTEM 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 CHROMOSOME 4 CLINICALLY SIGNIFICANT: MNSS MNS BLOOD GROUP SYSTEM M AND N S, S, AND U • • • • • CODED BY GLYCOPHORIN A CODED BY GLYCOPHORIN B • MEMBRANE STRUCTURE IS CALLED SIALOGLYCOPHORIN A • MEMBRANE STRUCTURE IS CALLED SIALOGLYCOPHORIN B • CONSISTS OF 131 AMINO ACIDS • CONSISTS OF 72 AMINO ACIDS M AND N DIFFER AT POSITIONS 1 AND 5 ON GLYCOPHORIN A (GPA) • SHOW DOSAGE • • HOMOZYGOUS INHERITANCE ENHANCES AGGLUTINATION [(M+N–) OR (M–N+)] • DESTROYED BY ENZYMES • S AND S DIFFER AT POSITION 29 • S HAS METHIONINE; S HAS THREONINE CAN BE DESTROYED BY SOME ENZYMES U ANTIGEN • • LOCATED NEAR MEMBRANE PRESENT WHEN S OR S IS INHERITED ABSENCE OF GLYCOPHORIN B (GPB) WOULD RESULT IN S–S–U– Table 7.16 Phenotype Frequencies in MNS System Antigen Phenotype frequencies (%) Whites Blacks M+ 78 74 N+ 72 75 S+ 55 31 s+ 89 93 U+ 99.9 99 From Reid ME, Lomas-Francis C, Olsson ML: The blood group antigen facts book, ed 3, San Diego, CA, 2012, Academic Press. • IgM and IgG • Rarely encountered in HDFN • Variable reactions depend on reagent pH (like it slightly acidic) Anti-M Anti-N • Rare IgM • N-like antibodies found in dialysis patients from formaldehydesterilized instruments Anti-S, anti-s, and anti-U • Clinically significant IgG • Anti-U is rare but can be found in S–s– persons (black population) What percent of the general population will be compatible with a patient with anti-__? A patient that inherited 3-D-galactosyl transferase and no other genes in the ABO and H system is? The Rh testing on a blood donor was negative at immediate spin. The tube was incubated at 37oC for 15 minutes. The tube was centrifuged and read macroscopically. The test was negative at 37oC. The tube was washed three times with saline, and two drops of AHG were added. After centrifugation, the tube yielded a 2+ reaction. How is this Rh type reported on the donor unit? All of the following statements are true concerning ABH soluble substances except: a. The first sugar in the precursor substance is N-acetylgalactosamine b. The precursor chain is type 2 (beta 1-4 linkage) c. ABH structures are glycoproteins d. L-fucosyltransferase production is regulated by the Se system 1 2 4 3 5 Carbohydrate antigensProtein antigens • Antibodies are generally naturally result after • Antibodies occurring, IgM immune stimulation, generally IgG • • • • • • • • • • ● ● ● – – – – – – Table 7.3 Common Phenotypes and Frequencies in the Kell Blood Group System Frequency (%) Phenotype White Black K–k+ 91 98 K+k– 0.2 Rare K+k+ 8.8 2 Kp(a+b–) Rare 0 Kp(a–b+) 97.7 100 Kp(a+b+) 2.3 Rare Js(a+b–) 0 1 Js(a–b+) 100 80 Js(a+b+) Rare 19 From Reid ME, Lomas-Francis C, Olsson Ml: The blood group antigen facts book, ed 3, San Diego, CA, 2012, Academic Press. Similar to the Rh system 2 major antigens • K (K1): less than 9% of the population • Little-k (K2/cellano): more than 98% of the population The K and k antigens are antithetical Well developed at birth The K (K1) antigen is very immunogenic (second to the D antigen) in stimulating antibody production Other antithetical antigens also exist in the Kell system Analogous to the Rh system: C/c and E/e Kp antigens Low frequency K/k Kpa/Kpb Jsa/Jsb High frequency • Kpa is a low-frequency antigen (only 2%) • Kpb is a high-frequency antigen (99.9%) Js antigens • Jsa (20% in blacks, 0.1% in Caucasians) • Jsb is a high-frequency antigen (80% to 100%) Kell antigens have disulfide-bonded regions on the glycoproteins This makes them sensitive to sulfhydryl reagents 2-mercaptoethanol (2ME) Dithiothreitol (DTT) 2aminoethylisothiouronium bromide (AET) Autosomal recessive Lacks all Kell system antigens (K0K0) Increased expression of Kx antigen As a result of red blood cell (RBC) immune stimulation, K0 individuals can develop antiKu (Ku is on RBCs that have Kell antigens) KX BLOOD GROUP SYSTEM • KX ANTIGEN IS PHENOTYPICALLY RELATED TO THE KELL SYSTEM BUT IS NOT GENETICALLY SIMILAR • INDIVIDUALS WHO LACK KX ANTIGEN MAY DEMONSTRATE RBC ABNORMALITIES = NEUROMUSCULAR ACANTHOCYTOSIS (MCLEOD PHENOTYPE) • SEEN IN MALES BECAUSE IT IS INHERITED ON THE X CHROMOSOME • REDUCED EXPRESSION OF ALL KELL ANTIGENS • • MCLEOD SYNDROME • • MCLEOD PHENOTYPE IS ATTRIBUTED TO MCLEOD SYNDROME MCLEOD SYNDROME SYMPTOMS • RBC ABNORMALITIES • MUSCULAR AND NEUROLOGIC • DEFECTS INCREASED CREATINE KINASE ASSOCIATED WITH • • • CHRONIC GRANULOMATOUS DISEASE MUSCULAR DYSTROPHY RETINITIS PIGMENTOSA ALLOANTIBODIES AGAINST KELL AND XK PROTEINS • ALL RBCS WITH KELL AND K0K0 ARE INCOMPATIBLE Immunoglobulin G (IgG) RBC stimulated (transfusion or pregnancy) Agglutinate best in the indirect antiglobulin test (IAT) Usually do not bind complement Associated with immediate and delayed hemolytic transfusion reactions (HTRs) and hemolytic disease of the fetus and newborn (HDFN) No effect when treated with enzymes Anti-K (K1) is the most common Compatibility: Red cells negative for the antigen and Extended Crossmatch compatible THE DUFFY SYSTEM CLINICALLY SIGNIFICANT: FYA, FYB Phenotype White Black Fy(a+b-) 17 9 Fy(a+b+) 49 1 Fy(a-b+) 34 22 Fy(a-b-) Rare 68 Fy3 and Fy5 = High Prevalence • On all cells except Fynull cells Antigens are well developed at birth Destroyed by enzymes Fya and Fyb • Codominant alleles • Most important for transfusion purposes IgG Do not bind complement DUFFY ANTIBODIES Stimulated by transfusion or pregnancy (not a common cause of HDFN) Implicated in acute and delayed HTRs Do not react with enzyme-treated RBCs  Antigens destroyed by Enzymes Shows dosage Compatibility: Red cells negative for the antigen and extended crossmatch compatible Most African Americans are Fy(a–b–) Certain malarial parasites (Plasmodium knowlesi and Plasmodium vivax) will not invade Fy(a–) and Fy(b–) negative cells Fya or Fyb acts as a receptor for the merozoite to attach to the RBC The Fy(a–b–) phenotype is found frequently in people from west and central Africa, supporting the theory of selective evolution THE KIDD SYSTEM CLINICALLY SIGNIFICANT : JKA, JKB Phenotype White Black Jk(a+b-) 28 57 Jk(a+b+) 49 34 Jk(a-b+) 23 9 Jk(a-b-) = Jk null Rare Rare • Autosomal recessive • Resistant to 2M urea (found in automated hematology analyzers) • Found in Polynesians and Finns In(Jk) • Autosomal dominant • • WELL DEVELOPED IN NEONATES • ONLY RARELY RESPONSIBLE FOR SEVERE HDFN 3 ANTIGENS: JKA, JKB, AND JK3 • • JK3 IS PRESENT WHENEVER JKA AND JKB ARE PRESENT KIDD NULL PHENOTYPES: JK(A–B–) • MAY PRODUCE ANTI-JK3 ANTIBODY KIDD BLOOD GROUP SYSTEM (1 OF 2) IgG Bind Complement causing intra and extravascular hemolysis MOST COMMON alloantibodies associated with delayed, severe HTRs Kidds play hide and seek Show dosage Enhanced by enzymes Compatibility: Red cells negative for the antigen and extended crossmatch compatible 19 antigens exist (chromosome 19) Weakly expressed on cord blood cells Most are highincidence antigens; Primary antigens include Lua and Lub antibodies are rare 92.4% Lu(a–b+) 7.4% Lu(a+b+) 0.2% Lu(a+b–) Lunull phenotype is rare, inherited recessively Not affected by enzymes • “InLu” • Carry trace amounts of Lutheran antigens • Do not make anti-Lu3 • Reduced expression of CD44, P1, I, AnWj, Mer2 and Inb Recessive X-Linked Inhibitor Type •X linked inhibitor to Lutheran due to GATA-1 mutations • Weak Lutheran antigen expression Recessive Type Lu(a-b-) • True null phenotype • Inherit two rare silent alleles LuLu • Lack Lutheran antigens • Normal expression of the antigens weakened with the dominant type • Can make potent anti-Luab Anti-Lu3 • Reacts with all RBCs except Lu(a-b-) • • • • • • • • • • MEMORIZE TABLE 8-23 SUMMARY OF ANTIBODY CHARACTERISTICS • • • • • • • • • • • • • • • • • • • • • • • • • • • • • •