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BLOOD GROUPS

BLOOD GROUPS. Meral Sonmezoglu , MD . Ass oc Professor of Infectious Dıseases. Early History of Transfusion. Harvey’s theory of circulation, 1628 Physick, Philadelphia, 1795 Blundell, England, 1818 Problems of sterility, coagulability, intravenous routes ignored.

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BLOOD GROUPS

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  1. BLOOD GROUPS Meral Sonmezoglu, MD. Assoc Professor of InfectiousDıseases

  2. Early History of Transfusion • Harvey’s theory of circulation, 1628 • Physick, Philadelphia, 1795 • Blundell, England, 1818 • Problems of sterility, coagulability, intravenous routes ignored

  3. Karl Landsteiner (1868-1943) • Discovered ABO blood groups, 1901 • Nobel Prize, 1930

  4. Classic Nine Blood Group Systems • ABO, 1901 • MN and P, 1927 • Rh, 1940 • Lutheran, 1945 • Kell, 1946 • Lewis, 1946 • Duffy, 1950 • Kidd, 1951

  5. All antigens fall into one of fourclassifications: 1. systems 2. collections 3. low incidence antigens (700 series) 4. high incidence antigens (901 series

  6. MajorBlood Group Systems

  7. OtherBlood Group Systems

  8. 030 RHAG Duclos Ola DSLK RHAG4 031 FORS FORS1 032 JR Jra 033 LAN Lan

  9. Developments 1951 to mid-1970s • Polymorphisms • Inter-relationships discovered • New systems added to “classic nine” • Diego; Cartwright; Xg; Scianna; Dombrock; Colton; LW; Chido/Rodgers; Hh; Kx; Gerbich; Cromer; Knops; Indian • Antigens added to Rh system • Antigen added to MN system • Monoclonal antibodies to develop better reagents • New techniques, including DNA libraries using RFLPs

  10. Blood Group System • Antigens produced by alleles at single genetic locus, or • Antigens produced by alleles at loci so closely linked that crossing-over never/rarely occurs • Alternative genes: alleles • Antigens: antithetical to each other

  11. Blood Group Collection • Group of antigens that display phenotypic association to each other, without definite genetic independence of all other systems

  12. Blood Group Antigens • 250 antigens, most assigned to one of 33 blood group systems • Approximately 50 antigens not yet assigned, categorized within “collections” (200 series) • Low incidence antigens (700 series) and high incidence antigens (901 series)

  13. Red Blood Cell Membrane Components

  14. RBC Antigens: Associated Functions • Membrane integrity (Kx, Rhnull, Diego) • Transport protein (Kidd) • Adhesion protein (Indian) • Complement regulator/inactivator • (Chido/Rodgers, Cromer, Knops) • Extracellular enzyme (Kell, Yta) • Receptor adhesion (Duffy) • Infectious disease (P globoside, Wrb)

  15. Carbohydrate-based Blood Groups and Collections • Genes control expression of an enzyme that attaches the immunodominant sugar to a precursor backbone on the RBC membrane • ABO • Ii Collection • Lewis • P • Globoside Collection

  16. ABO System • H antigen: H substance is the precursor molecule; fucose bound to subterminal sugar of the oligosaccharide chain • Fucosyltransferase gene for H: chromosome 19 • Subgroups of A and B exist; A subgroups more common

  17. H Antigen • The H gene codes for an enzyme that adds the sugar fucose to the terminal sugar of a precursor substance (PS) • The precursor substance (proteins and lipids) is formed on an oligosaccharide chain (the basic structure)

  18. RBC Precursor Structure RBC Glucose Galactose Precursor Substance (stays the same) N-acetylglucosamine Galactose

  19. Formation of the H antigen RBC Glucose H antigen Galactose N-acetylglucosamine Galactose Fucose

  20. Type 2 Precursor Chain

  21. Formation of H Antigen

  22. ABO System (2) • A antigen: terminal sugar N-acetylgalactosamine • B antigen: terminal sugar galactose • No O antigen: O gene produces nonfunctional transferase with absence of both A and B • Glycosyltransferase genes: chromosome 9

  23. Formation of A Antigen

  24. Formation of B Antigen

  25. ABO System (3) • Anti-A and anti-B: naturally occurring, clinically significant; can cause hemolytic transfusion reactions (HTR) and hemolytic disease of the newborn (HDN) • Bombay: normal A and B genes, lack functional H gene, cannot produce H substance, lack A and B antigens, phenotype as group O • Bombay individuals (Oh) have potent anti-H reacting with all RBCs; need rare-donor Bombay RBCs

  26. Ii Blood Group Collection • Same oligosaccharide chains as the A, B, and H antigens, but the interior portion • i antigen, unbranched, on neonatal cells • I antigen, branched, forms during first 2 years of life • Auto-anti-I: mycoplasma infection • Auto-anti-i: Epstein-Barr virus infection

  27. Lewis System • Soluble plasma antigens, adsorbed reversibly onto RBCs • Transfused RBCs assume Lewis phenotype of recipient • Anti-Lea: most are insignificant; never cause HDN • Anti-Leb: insignificant

  28. P Blood Group System • Single antigen, P1 • Individuals lacking P1 antigen are P2 phenotype • Anti-P1 naturally occurring, IgM, usually insignificant

  29. Globoside Blood Group Collection • Pk and P antigens • P is high incidence antigen • Pk antigen is rare • Anti-P: significant IgM, naturally occurring, can cause both HTR and HDN • Donath-Landsteiner antibody is IgG auto-anti-P, biphasic, causing paroxysmal cold hemoglobinuria (PCH)

  30. Polypeptide Blood Groups • Protein antigens under direct genetic control • MNS • Rh • Kell • Kidd • Duffy • Lutheran • Others • Chido/Rodgers • Bg • Xga • Diego

  31. MNS Blood Group System • Major antigens are peptides called glycophorins: • Glycophorin A: M, N • Glycophorin B: S, s, and U • Genes for glycophorins A and B closely linked, chromosome 4 • u denotes absence of U, a high incidence Ag • In absence of U, cells are always S-s- • Patients with anti-U require U-negative blood

  32. MNS Blood Group System (2) • Ena is high incidence Ag on glycophorin A • Ena-negative persons lack glycophorin A, with neither M nor N expression • Ena-negative persons with anti-Ena require rare blood, Ena-negative

  33. MNS Blood Group System (3) • Anti-M: frequent, naturally occurring, either IgM or IgG, rarely significant; unless IgG, then can cause HDN • Anti-N: almost always IgM, not significant • If anti-M/N causes agglutination at 37 C, then use antigen-negative blood; otherwise crossmatch-compatible sufficient

  34. MNS Blood Group System (4) • Anti-S and anti-s both cause HTR and HDN • Patients with anti-S/s will need antigen-negative blood • Anti-U and anti-Ena are both IgG and significant; rare antigen-negative blood required

  35. Rh Blood Group System • Rh proteins encoded by two linked genes on chromosome 1: RHD and RHCE, a haplotype unit • Major antigens: D, C, c, E, and e • D: epitope on RhD protein • C,c and E,e: antithetical antigens on RhCE protein • No d antigen exists

  36. Rh Blood Group System (2) • Rh-positive (85%) and Rh-negative (15%) refer to presence or absence of the D antigen • D antigen most immunogenic of all non-ABO antigens • Anti-D can cause HTR and severe HDN • Nomenclature is confusing and complex: • Fisher-Race: Dd, Cc, Ee • Wiener: R=D, r=absence of D; superscripts (numbers and primes) for Cc or Ee, numbers with R, primes with r

  37. Rh Blood Group System (3) • Weak D (Du): D antigen in reduced quantity • Individuals with weak D are Rh-positive • Individuals with weak D do not make D alloantibodies • Partial D: some epitopes of D antigen missing • Individuals may produce alloanti-D • Individuals are considered Rh-positive • Recipients should receive Rh-negative RBCs

  38. Rh Blood Group System (4) • Rhnull: all Rh antigens absent from RBC surface • Mild hemolytic anemia with stomatocytosis and increased osmotic fragility • Two mutations identified: • RhAG gene for Rh-associated glycoprotein, required for stability/localization of the Rh proteins • RHCE gene mutation in Rh-negative individuals • Antibodies to Rh antigens: usually IgG, reactive at 37 C, and cause HTR and HDN

  39. Kell Blood Group System • More than 20 antigens • Major antigens: K (Kell) and k (Cellano) • Only the D antigen of Rh system is more immunogenic than K among all non-ABO antigens • Antibodies are clinically significant • Other antithetical pairs: Kpa/Kpb, Jsa/Jsb

  40. Kell Blood Group System (2) • In absence of Kx, called the McLeod syndrome, amount of Kell system antigens on RBCs and granulocytes is significantly reduced • Kell and Kx proteins closely associated, Kx protein needed for Kell stability • McLeod syndrome: shortened RBC survival, chronic granulomatous disease, muscular dystrophy, retinitis pigmentosa

  41. Kell Blood Group System (3) • Kell antibodies: immune-stimulated IgG, significant for HTR and HDN • Anti-K most common immune RBC antibody outside ABO and Rh systems, accounting for 1/3 of alloantibodies

  42. Kidd Blood Group System • Primary antigens: Jka and Jkb, encoded by two codominant alleles • Rare: Jknull [Jk(a-b-)] can make anti-Jk3 • Antibodies are IgG immune stimulated, can cause HTR and HDN • Antibodies notorious for being short-lived, and, non-detected, are associated with delayed HTR

  43. Duffy Blood Group System • Major antigens: Fya and Fyb, on intramembranous RBC membrane glycoprotein • Plasmodium vivax receptor; Fy(a-b-) individuals resistant to P. vivax malaria (60% African Americans) • Antibodies are immune stimulated, clinically significant for HTR and HDN

  44. Example 7 Problem: Causes: Resolution:

  45. Example 6 • if alloantibody – antibody ID techniques • if autoantibody – special procedures (minicold panel, prewarming techniques

  46. References • Rudmann, S. V. (2005). Textbook of Blood Banking and Transfusion Medicine (2nd Ed.). Philadelphia, PA: Elsevier Saunders. • Blaney, K. D. and Howard, P. R. (2000). Basic & Applied Concepts of Immunohematology. St. Louis, MO: Mosby, Inc.

  47. Blood Grouping using gel cards

  48. Antibody screening • Important that we can detect immune antibodies in antenatal and patients requiring transfusion • Immune antibodies are IgG and don’t readily cause clumping (agglutination of red cells) • We need to use anti-IgG in our tests - Coombs Test

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