Other Blood Group Systems

1. Other Blood Group Systems Terry Kotrla, MS, MT(ASCP)BB

2. Introduction • Over 500 blood group antigens • “High incidence”, “public” or “high frequency” antigens are those present on almost every person’s red blood cells • “Low incidence”, “private” or “low frequency” antigens are present on very, very few individuals red blood cells

3. Introduction • Each known antigen initially identified through the detection of its specific antibody in the serum. • Knowledge of serologic behavior and characteristics of blood group antibodies is CRITICAL for identification

4. Introduction • Essential when evaluating antibody screen and panel studies. • Considerations given to: • Phase of reactivity • Antibody class involved • Ability to cause HDFN and HTR

5. I Blood Group • Related to ABO and Lewis by its biochemical structure • Two antigens: I and i • Fetal RBCs rich in i antigen and lack I antigen. • First 2 years I develops, lose i • Anti-I reacts most strongly with adult cells, negative or weakly with cord RBCs • Strength of I antigen varies on adult cells • Rare instances I never develops.

6. I Blood Group • Anti-I is associated with cold agglutinin hemagglutinin disease • Decreased expression of I and increased expression of i antigens is observed in: • oncogenesis, • thalassemias, • sickle cell anemias, • associated with congenital cataracts in Asian populations.

7. I Blood Group • Antibodies: anti-I anti-I • Anti-I • Cause of non-specific agglutination in tests performed at RT • Positive reactions with all cells tested: reverse, antibody screen and crossmatches • May cause ABO discrepancy • Can be detected in serum of most normal adults if serum is tested at 4C • Associated with atypical pneumonia caused by M. pneumoniae , cold agglutinin titers used to monitor the disease. • May cause hemolytic anemia when present in high titers

8. I Blood Group • Anti-i associated with certain diseases • Infectious mononucleosis • Epstein-Barr virus • Cytomegalovirus • Antibody is rarely encountered

9. I Blood Group • Clinical Significance • Usually benign • Clinically significant examples seen in Cold Agglutinin Syndrome (CAS) • Antibodies are of high titer (1000>) • High thermal amplitude • Cause hemolytic anemia • Transfuse blood through blood warmer • Cannot cause HDFN • Does not cause HTR

10. I Blood Group • Serological Confirmation • Test serum agains 3 adult O RBCs and 3 cord RBCs and an auto-control • Adult cells and auto-control = positive • Cord RBCs = negative/very weak positive • Prewarmed technique will eliminate reactivity of most examples • Reactivity enhanced using enzyme treated cells

11. I Blood Group • Very strong examples of anti-I may react at AHG and require cold autoabsorption or rabbit erythrocyte stroma test (REST) to rule out presence of other antibodies. • Collect EDTA blood samples, place at 37C • Harvest EDTA cells, wash with 37C saline • Place clotted blood sample at 4C, separate serum • Add 1 mL serum to 1mL rbcs, incubate at 4C for 1 hour • Harvest serum and test against screen cells, if negative, continue screen, if positive repeat absorption with new aliquot of RBCs

12. Lewis System • Major antigens Lea and Leb , other antigens include Lec, Led and Lex • Antigens ARE NOT intrinsic to RBCs but are absorbed from the plasma and inserted into RBC membrane.

13. Lewis System • Antigenic Development • Genetic control reside in single gene “Le” • Amorph le, if homozygous will not have Lewis antigens • Lea formed first, then modified to form Leb which is adsorbed preferentially over Lea • Lewis phenotype of RBC can be changed by incubating with plasma containing Lea or Leb glycoplipid.

14. Lewis System

15. Lewis System • Lewis antigens in infants • Antigens absent or extremely weak at birth • Expression of Leb gradual • Birth Le (a-b-) • 2 months Le(a+b-) • 12 to 18 months Le(a+b+) • 2 to 3 years Le (a-b+)

16. Lewis System • Lewis antigens and pregnancy • Antigen strength may decline dramatically • Transiently Le (a-b-) may produce Lewis antibodies during pregnancy • Antigens return after delivery and antibodies disappear

17. Lewis System • Interaction of Le, Se and H Genes • lele will not have Lewis antigens, but if Se present will have A, B and H in secrections • Genotype se/se and have one Lewis antigen will have Lea in their secretions but no A, B or H.

18. Lewis System

19. Lewis System • Lewis Antibodies • Almost always IgM, react strongly at RT, may cause ABO discrepancy if reverse cells have Lewis antigen. • Occur almost exclusively in Le (a-b-) and production of anti-Lea AND –Leb not unusual • Anti-Lea frequently encountered, anti-Leb rarely encountered.

20. Lewis System • Lewis Antibodies • Although most react at RT reactivity may be seen at 37C, but is weaker and may be weakly reactive at AHG • Can bind complement and cause IN-VITRO hemolysis, most often with enzyme treated cells • Because antibodies are IgM and antigens are poorly developed at birth antibodies NOT implicated in HDFN.

21. Lewis System • Lewis antibodies • Can be neutralized in-vitro by additions of Lewis Substance • Le antigens are present in secretions • Add to serum with Lewis antibodies and the antibodies will be bound to the soluble Lewis antigens • Useful when multiple antibodies are present and 1 is a Lewis, eliminates the activity of the antibody

22. Lewis System • Transfusion Practice • Transfused RBCs will acquire the Lewis phenotype of the recipient within a few days • Lewis antibodies in patient will be neutralized by Lewis substance in donor plasma • Lewis antibodies rarely cause in-vivo hemolysis • It is not necessary to phenotype donors for Lewis antigens prior to transfusion, give crossmatch compatible

23. P Blood Group • Discovered 1927 when Landsteiner immunized rabbits with human RBCs • Initially named “P” but as complexity of P blood group was discovered renamed “P1” • RBCs lacking P1 are P2 • Other P phenotypes exist but are rare(<1%): P, P1k and P2k