2. Blood group : is a classification of blood based on the presence or absence of inherited antigenic substances on the surface of red blood cells. These antigens may be proteins or carbohydrates or glycoproteins depending on the blood group system. Blood antigens controlled by genes that located on the some chromosomes. A total of 30 human blood group systems are now recognized. ( table 1 and figure 1 and 2 )

3. ISBT Human Blood Group Systems Number/NameAbbreviation 001ABOABO 002MNSMNS 003P1P1 004RhRH 005LutheranLU 006KellKEL 007LewisLE 008DuffyFY 009KiddJK 010DiegoDI 011CartwrightYT 012XGXG 013SciannaSC 014DombrockDO 015ColtonCO 016Landsteiner-WienerLW 017Chido/RodgersCH/RG 018HhH 019KxXK 020GerbichGE 021CromerCROM 022KnopsKN 023IndianIN 024OkOK 025RaphRAPH 026JMHJMH 027II 028PP 29GILGIL 30RhAGRHAG 30 blood group systems 308 blood group antigens 1140 blood group alleles RBC

5. ABO – System : Discovery of the ABO system by the Austrian Karl Landsteiner in 1901 marked the beginning of safe blood transfusion. There are 4 major ABO- blood types designated by the antigens present on RBCs : 1- Blood group A : Individuals have the A antigen on the surface of their RBCs, and blood serum containing Anti-B antibodies. Therefore, a group A individual can only receive blood from individuals of groups A or O ( with A being preferable ) and can donate blood to individuals of groups A or AB.

6. 2- Blood group B : Individuals have the B antigen on their surface of their RBCs, and blood serum containing Anti-A antibodies. Therefore, a group B individual can only receive blood from individuals of groups B or O ( with B being preferable ) and can donate blood to individuals of groups B or AB. 3- Blood group AB : Individuals have both A and B antigens on the surface of their RBCs, and their blood serum does not contain any antibodies against either A or B antigen. Therefore, an individual with type AB blood can receive blood from any group ( with AB being preferable ), but can only donate blood to another group AB individual. (Universal recipient)

7. 4- Blood group O : Individuals do not have either A or B antigens on the surface of their RBCs, but their blood serum contains Anti- A and Anti-B antibodies. Therefore, a group O individual can only receive blood from a group O individual, but they can donate blood to individuals of any ABO blood group ( A, B, O, or AB ). ( Universal donor ). ( Table 2 ).

9. Table 2 : Blood Transfusion Compatibilities for the ABO Blood Groups Transfusion can be given to Transfusion can be accepted from Antibodies present in serum Antigens present on RBCs Blood Group A, ABA, OAnti- B A galactosamine A B, ABB, OAnti- A(B (galactoseB AB Universal recipient A, B, AB, ONone A galactosamine Plus B galactose AB O, A, B, AB Universal donor O Anti-A plus Anti- B NoneO

10. Genetics of ABO system The ABO blood type is controlled by the ABO gene that located on chromosome 9. This gene responsible for the producing of the A and B antigens and the gene is donated by the letter I. It has 3 alleles I A, I B, I O. The gene encodes a glycosyltransferase enzyme.

11. People with blood type A have A antigen on the surfaces of their red blood cells and may be of genotype I A I A or I A I O. People with blood type B have B antigen on their red blood cell surfaces and may be of genotype I B I B or I B I O. People with the rare blood type AB have both antigens A and B on their cell surfaces and are genotype I A I B. People with blood type O have neither antigen and are genotype I O I O. ( Table 3 ) Each person has 2 copies of genes coding for their ABO blood group ( one maternal and one paternal in origin ) ( Table 4 )

12. Table 3 : Genotypes and the Corresponding Phenotypes ( Blood Group Types ) for the ABO Locus in Humans. Frequency in Population PhenotypeActivityGenotype 42%Aα-3-N-acetyI-D- galactosaminyltransferase I A I A, I A I O 8%Bα-3-D- galactocyltransferase I B I B, I B I O 3%AB Both enzymesI A I B 47%O NoneIO IOIO IO

13. Inheritance of Blood Types These charts show the possible blood type results for offspring. Mothers's Type Blood Type ABBAO A, BO, BO, AOO Fathers' Type A, B, ABO, A, B, ABO, A A A, B, ABO, BO, A, B, ABO, BB A, B, AB A, BAB Mother's Type Rh Factor Rh -Rh + Rh +, Rh -Rh +, Rh +Rh + Father's Type Rh -Rh +, Rh -Rh -

14. Codominance : A heterozygote in which both alleles are fully expressed. This means that if a person inherited one A group gene and one B group gene their red cells would possess both the A and B blood group antigens. The A and B alleles are codominant, and both A and B are completely dominant to O. ( figure 4 )

15. The Origin of ABO Antigens : The A and B genes each code for an enzyme (glycosyl transferases ) that adds aterminal carbohydrate to RBC receptors during maturation. ( Figrue 5 and 6 ). The A gene codes for an enzyme N- acetylgalactosaminyl transferase that adds N- acetylgalactosamine to the RBC receptors ( blood type A ) ; The B gene codes for an enzyme D- galactosyl transferase that adds D- galactose to the RBC receptors ( blood type B ) ; RBCs of type AB contain both enzymes that add both carbohydrates ; and RBCs of type O lack the genes and enzymes to add a terminal molecule. ( Table 5 ).

16. Figure (2) The Origin of ABO Antigens :

17. The Origin of ABO Antigens

19. ABO antibodies : Almost all normal healthy individuals about 3-6 months of age have naturally occurring antibodies to the ABO antigens that they lack. Antibodies produced to non self. anti- A and anti- B antibodies are mostly IgM class.( figure 7 )

20. Blood Transfusions : The differences in human blood are due to the presence or absence of certain antigens and antibodies, therefore a number of laboratory tests must be completed before blood can be transfused : 1- Blood Typing : The individual blood types of donor and recipient must be determined Using a standard technique, drops of blood are mixed with antisera that contain antibodies against the A and B and RH (D) antigens, and are then observed for the evidence of agglutination. ( Figure 8 and 9 ). 2- Screening for possible infectious agents that could be transmitted by blood transfusion such as : Human Immunodeficiency Virus ( HIV ), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) and some bacteria and parasites.

21. Blood Typing Test

22. This blood is B+

23. 3- Crossmatch ( Compatibility Test ) : The aim of cross matching is to ensure that the blood of a recipient does not contain antibodies that will be able to react with and destroy transfused ( donor ) RBCs. For example : If the donor is A type and the recipient is B type.The RBCs of the type A donor contain antigen A, while the serum of the type B recipient contains anti-A antibodies that can agglutinate donor RBCs ( agglutination : clumping of RBCs when attached to an antibody) Agglutinated RBCs can clog blood vessels and stop circulation in vital organs. (Transfusion reaction :occurs When incompatible blood is transfused, specifically if antibodies in the recipient’s serum cause rapid RBC destruction in the proposed donor ). ( Figure 10 ).

25. The primary purpose of the major cross match or compatibility test, is to prevent a possible transfusion reaction. To begin the crossmatch, blood from a donor with the same ABO and Rh type as the recipient is selected. In a test tube, serum from the patient is mixed with RBCs from the donor. If clumping occurs, the blood is not compatible. If clumping does not occur the blood is compatible. ( Figure 11 and 12 ). CompatibleNot compatible

27. Table (4) Blood Transfusions :

28. RH- System RH blood types ( Rhesus factor ) were discovered in 1940 by Karl Landsteiner and Alexander Wiener. Like the ABO system, the RH system is defined on the basis of antigens that are present on erythrocyte surfaces. Rh factor is a protein found on most peoples RBCs.

29. Genetics of RH- System : The RH locus is located on the chromosome 1. It contains two closely linked genes RHD and RHCE. RH D gene encodes D antigen( transmembrane proteins ) RHCE gene encodes CE antigens. Figure 14 RH antigens are transmembrane proteins with loops exposed at the surface of red blood cells.

30. Person with the DD or Dd genotype have the RH antigen ( D antigen ) on their erythrocytes and are termed RH- Positive. person with genotype dd are RH-Negative and do not have the RH antigen. ( Figure 15 ) Frequency in population RH- Positive 85%, RH- Negative 15%.

31. Importance of RH system : 1.RH D antigen is the most immunogenic red cell antigen after A and B antigen. 2.RH D antibody can cause hemolytic transfusion reactions and hemolytic disease of newborn or erythroblastosis fetalis. Anti- RH antibodies : Anti RH antibodies of the system are not normaly present in the system but can be produced if an individual with RH - is exposed to RH + antigen usually through pregnancy or incompatible blood transfusion.

32. Hemolytic Disease of Newborn HDN : Is a disease in which the fetus red blood cells have been lysed by mothers antibodies, caused by blood group incompatibility between mother and child. 1 - RH Hemolytic Disease of Newborn : Type of anemia in which the RBCs of a fetus are destroyed by antibodies produced by the mother resulting from a blood group incompatibility between the fetus and its mother. This incompatibility arises when the fetus inherits a certain blood factor gene from the father that is absent in the mother. RH HDN Results When RH negative mother becomes pregnant with RH positive child ( the child having inherited RHD antigen from the father ). If the father genotype is DD, all of their children will be RH-Positive. If the father genotype is Dd, half of their children will be RH-Positive.

33. In the First Pregnancy with RH Positive fetus : RH + antigens from the developing fetus can enter the mothers blood during delivery. ( Figure 16 ) After birth or abortion : The mother will produce anti RH antibodies In next Pregnancy with RH Positive baby : Mother anti RH antibodies IgG will cross the placenta and damage fetal red blood cells and cause disease called Hemolytic Disease of Newborn.

34. RH Hemolytic Disease of Newborn :

35. Preventing Hemolytic Disease of Newborn (HDN): RH negative mother is givin injections of anti-RH D antibodies D gamma globulin called ( Rhogam ) around the 28 th week of pregnancy and again with in 72 hours after the delivery of the RH Positive baby. This must be done for the first and all subsequent pregnancies. The injected antibodies quickly agglutinate any fetal red blood cells as they enter the mother’s blood before they stimulate production of anti- RH antibodies.

36. 2- ABO Hemolytic Disease of Newborn : HDN can also be caused by an incompatibility of ABO blood group. It arises when a mother with blood type O becomes pregnant with a fetus with a different blood group ( A or B ). Anti- A and anti B- antibodies are usually IgM and do not pass through the placenta, but some mothers naturally have IgG anti- A or IgG anti-B antibodies which can pass through the placenta and hemolyse fetal RBCs. In contrast to Rh HDN, ABO disease may be found in the first pregnancy and may or may not affect subsequent pregnancies.

37. Inheritance of ABO and RH blood groups : ABO & RH genes are not linked, ABO & RH (D ) type are inherited independently. For example : An A RH ( D ) positive mother and a B RH ( D ) positive father could have an O RH ( D ) negative child.