Blood groups and transfusion Dr. Gamal Badr PhD in Immunology (Paris Sud University, France) Associate Professor of Immunology Assiut University, Egypt Tel: Fax: s: or Websites: orcid.org/

2 Blood Composition

ABO Biochemical Basics Blood group antigens are actually sugars attached to the red blood cell. Antigens are “built” onto the red cell. Individuals inherit a gene which codes for specific sugar(s) to be added to the red cell. The type of sugar added determines the blood group.

diagram illustrates the terminal sugar for each blood group.

ABO Blood Group Basics All normal blood groups have “H”. If only H is added to the red blood cell the person is group O. If N-acetylgalactosamine is added to H, the person is group A. If D-galactose is added to H, the person is group B. If both N-acetylgalactosamine and D-galactose are added the person is AB.

ABO Type Frequencies In Turkey ABO TypePer Cent O35% A42% B16% AB7%

Landsteiner’s Rule Individual’s will form immune antibodies to ABO blood group antigens they do not possess. ABO antibodies are immune and will result in destroying incompatible cells which may result in the death of the recipient. When we donate blood or have surgery, a small sample is usually taken in advance for at least ABO and Rh systems typing. If you are O+, the O is your ABO type and the + is your Rh type. It is possible to be A, B, AB, or O as well as Rh+ or Rh-. You inherited your blood types from your parents and the environment in which you live cannot change them.

8 Blood Groups and Transfusions A.After mixed success with transfusions, scientists determined that blood was of different types and only certain combinations were compatible. B.Antigens and Antibodies 1. Clumping of red blood cells following transfusion is called agglutination. 2.Agglutination is due to the interaction of proteins on the surfaces of RBCs (antigens) with certain antibodies carried in the plasma. 3.Only a few of the antigens on RBCs produce transfusion reactions. These include the ABO group and Rh group.

9 C.ABO Blood Group 1.Type A blood has A antigens on RBCs and anti-B antibodies in the plasma. 2.Type B blood has B antigens on RBCs and anti-A antibodies in the plasma. 3.Type AB blood has both A and B antigens, but no antibodies in the plasma. 4.Type O blood has neither antigen, but both types of antibodies in the plasma. Adverse transfusion reactions are avoided by preventing the mixing of blood that contains matching antigens and antibodies due to the agglutination of RBCs.

10

Genetics Two genes inherited, one from each parent. Individual who is A or B may be homozygous or heterozygous for the antigen. Heterozygous: AO or BO Homozygous: AA or BB Phenotype is the actual expression of the genotype, ie, group A Genotype are the actual inherited genes which can only be determined by family studies, ie, AO.

Example of Determining Genotype Mother’s phenotype is group A, genotype AO Father’s phenotype is group B, genotype BO BO AAB 25%AO 25% (Group A) OBO 25% (Group B)OO 25% (Group O)

Other Examples MomDadOffspring Blood Group AABB100% AB BOOO50% each of B or O OO 100% O OOAO50% each of A or O

Inheritance of ABO blood group Parents’ Offspring possible Offspring impossible blood group blood group blood group O×O O A, B, AB A×A O, A B, AB A×O O, A B, AB B×B O, B A, AB B×O O, B A, AB B×A O, A, B, AB ____ AB×O A, B O, AB AB×A A, B, AB O AB×B A, B, AB O AB×AB A, B, AB O Genetic relationship of ABO blood group

Group O Approximately 45% of the population is group O. No A or B antigens present, think of as “0” antigens present. These individuals form potent anti-A and anti-B antibodies which circulate in the blood plasma at all times.

Group O For red blood cell transfusions Group O individuals CAN ONLY RECEIVE Group O. Transfusion of any other blood group will probably result in death of the recipient due to the anti-A and anti-B antibodies present in their blood plasma. As DONORS, this blood group is considered the “universal donor” since there are no A or B antigens present this blood can be transfused safely to all other blood groups.

Group A Approximately 40% of the population is group A. No B antigens present. These individuals form potent anti-B antibodies which circulate in the blood plasma at all times.

Group A For RBCs transfusions Group A individuals can receive either Group A or Group O Transfusion of Group B will result in death of the recipient due to the anti-B antibodies present in their blood plasma reacting with the B antigens present on the transfused red blood cells.

Group B Approximately 11% of the population is group B. No A antigens present. These individuals form potent anti- A antibodies which circulate in the blood plasma at all times.

Group B For red blood cell transfusions Group B individuals can receive either Group B or Group O Transfusion of Group A will result in death of the recipient due to the anti-A antibodies present in their blood plasma reacting with the A antigens present on the transfused red blood cells.

Group AB Approximately 4% of the population is group AB. Both A and B antigens present. These individuals possess no ABO antibodies.

Group AB For RBCs transfusions Group AB can receive ANY blood Group. Considered the “Universal Recipient”. Because they have no anti-A, can receive group A, no anti-B, can receive group B. So even though the rarest blood group, finding compatible blood is not a problem.

Hemolysis If an individual is transfused with an incompatible blood group, destruction of the red blood cells will occur. This may result in the death of the recipient.

Summary Blood GroupAntigens on cellAntibodies in plasma Transfuse with group AAAnti-BA or O BBAnti-AB or O ABA and BnoneAB, A, B or O ONoneAnti-A & BO

Rh (D) Antigen Of next importance is the Rh type.  Term “Rh” is a misnomer.  Rh is a blood group system with many antigens, one of which is D.  Re-education of public is difficult. Rh refers to the presence or absence of the D antigen on the red blood cell.  So, for example, some people in group A will have the D antigen, and will therefore be classed as A+ (or A positive). While the ones that don't, are A- (or A negative). And so it goes for groups B, AB and O.

Rh (D) Antigen Unlike the ABO blood group system, individuals who lack the D antigen do not naturally make it. Production of antibody to D requires exposure to the antigen. The D antigen is very immunogenic, ie, individuals exposed to it will very likely make an antibody to it. For transfusion purposes Rh (D) negative individuals must receive Rh negative blood. Rh (D) positive individuals can receive EITHER Rh (D) negative or Rh (D) positive blood.

Rh (D) Antigen The most important patient population to consider is females of child- bearing age. If immunized to Rh (D) antigen the antibody can cross the placenta and destroy Rh (D) positive fetal cells resulting in death. This is why Rh negative women are given Rhogam (IgG anti-RhD) antibodies after birth of Rh positive baby to prevent hemolytic disease of the newborn.

28 Hemolytic Disease of the Neborn – How it Occurs

Slide Blood Typing Blood typing is determining the blood group using Abs anti-A and anti-B. If an RBC contains the A antigen this RBC will be agglutinated by anti-A, a positive reaction. If an RBC does not have the A antigen there will be no clumping, a negative reaction. Agglutination No agglutination

Determine the ABO blood group

Blood Typing Anti-AAnti-BBlood Group negative O positivenegativeA positiveB AB

People with blood group O are called "universal donors" and people with blood group AB are called "universal receivers" Blood transfusions – who can receive blood from whom?

Blood GroupAntigensAntibodies Can give blood to Can receive blood from ABA and BNoneABAB, A, B, O AABA and ABA and O BBAB and ABB and O ONoneA and BAB, A, B, OO

 The field of organ transplantation has made remarkable progress in a short period of time.  Transplantation has evolved to become the treatment of choice for end- stage organ failure resulting from almost any of a wide variety of causes.  Transplantation of the kidney, liver, pancreas, intestine, heart, and lungs has now become common place in all parts of the world. PRINCIPALES OF ORGAN TRANSPLANTATION Transplantation is the act of transferring an organ, tissue, or cell from one place to another.

1-Autotransplants: involve the transfer of tissue or organs from one part of an individual to another part of the same individual. They are the most common type of transplants and include skin grafts and vein grafts. NO immunosuppression is required 2-Allotransplants : involve transfer from one individual to a different individual of the same species—the most common scenario for most solid organ transplants performed today. Immunosuppression is required for allograft recipients to prevent rejection. 3- Xenotransplants: involve transfer across species barriers. Currently, xenotransplants are largely relegated to the laboratory, given the complex, potent immunologic barriers to success. Types of organ transplantation

Transplant Antigens  The main antigens involved in triggering rejection are coded for by a group of genes known as the major histocompatibility complex (MHC). In humans, the MHC complex is known as the human leukocyte antigen (HLA) system. It comprises a series of genes located on chromosome 6.  HLA molecules can initiate rejection and graft damage, via humoral or cellular mechanisms:  Humoral rejection mediated by recipient's Abs. (e.g. blood transfusion, previous transplant, or pregnancy)  Cellular rejection is the more common type of rejection after organ transplants. Mediated by T lymphocytes, it results from their activation and proliferation after exposure to donor MHC molecules.

Complications Of Organ Transplantation 1- Rejection 2-Malignancy

1- Rejection:  Graft rejection is a complex process involving several components, including T lymphocytes, B lymphocytes, macrophages, and cytokines, with resultant local inflammatory injury and graft damage.  Rejection can be classified into the following types based on timing and pathogenesis: Hyperacute, Acute, and Chronic.

A-Hyperacute rejection:  This type of rejection, which usually occurs within minutes post transplant, is because of the presence of preformed antibodies in the recipient, antibodies that are specific to the donor.  These bind to the vascular endothelium in the graft and activate the complement cascade, leading to platelet activation and to diffuse intravascular coagulation. The result is a swollen, darkened graft, which undergoes ischemic necrosis.

B-Acute rejection:  This used to be the most common type of rejection, but with modern immunosuppression it is becoming less and less common. Acute rejection is usually seen within days to a few months post transplant. It is predominantly a cell-mediated process, with lymphocytes being the main cells involved. C-Chronic rejection:  is form of rejection occurs months to years post transplant. Now that short term graft survival rates have improved so markedly, chronic rejection is an increasingly common problem.

IMMUNOSUPPRESSION  The success of modern transplantation is in large part because of the successful development of effective immunosuppressive agents.  Two types of immunosuppression are used in transplantation: 1. Induction of immunosuppression. refers to the drugs administered immediately post transplant to induce immunosuppression. 2. Maintenance immunosuppression. refers to the drugs administered to maintain immunosuppression by antibodies, Corticosteroids and cyclosporines.

2-Malignancy:  Transplant recipients are at increased risk for developing certain types of de novo malignancies, including non melanomatous skin cancers (3–7-fold increased risk), lymphoproliferative disease (2–3-fold increased risk) and gynecologic and urologic cancers.  The most common malignancies in transplant recipients are skin cancers. They tend to be located on sun-exposed areas and are usually squamous or basal cell carcinomas.  Patients are encouraged to use sunscreen liberally and avoid significant sun exposure.