Blood physiology

Blood Group

Lec 10 26 Nov, 2017
Prof.Dr.Baybeen
Objectives:
1.ABO System
ABO Transfusion Reaction

2.Rh Blood Type

Rh transfusion reaction

The antigens on the surface of erythrocytes have been categorized into blood groups and more than 35 blood groups, most of which are rare, have been identified. The ABO blood group and Rh blood group are among the most important. Other well known blood group includes Lewis, Duffy, Kidd, Kell, Lutheran, and MNSs. ABO and Rh-blood groups of antigens are more likely than the others to cause blood transfusion reactions.

ABO Blood Systems

Objectives:
ABO System
ABO Transfusion Reaction
Agglutinogens The membrane of human red cells contains a variety of blood group antigens, which are also called agglutinogens. The most important and best known of these are the A and B antigens, The A. and B antigens are actually complex oligosaccharides that differ in their terminal sugar. The A and B antigens are inherited as Mendelian dominants and individuals are divided into four major blood types depending on the presence or absence of the A antigen, and B antigen
1. Type A. 2. Type B. 3.Type AB. 4. Type O. Subgroups of blood types of A and B have been described, the most important being A1 and A2.These antigens are also found in many tissues in addition to blood, these include salivary glands, saliva, pancreas, kidney, liver, lungs, testes, semen and amniotic fluid.
Agglutinins (Antibodies): Antibodies against red cell agglutinogens are called agglutinins which are present in the plasma. The agglutinins are gamma globulins and they are produced by plasma cells (which are originated from B-lymphocytes) system. Most of them are IgM (have 10 binding sites) and IgG (have two binding sites).The presence of A and B antibodies in the blood is not clearly understood. An infant develop antibodies against the antigens not present in their own cells.
The type of agglutinogen, agglutinin, and frequency (%) in each type of :
1. Blood group A: has A antigens on the erythrocytes and antibodies B in the plasma .The percentage (%) of this group is 41 blood group.
2. Blood group B: has antigens B on the erythrocytes and antibodies A in the plasma. The % is 10.
3. Blood group AB: has both types of antigens A and B on the erythrocytes and has neither type of agglutinins in the plasma. The % is 4.This group is called Universal Recipient (a recipient receives the blood). Blood AB group receives the blood from all groups but cannot give blood to any type except a person of blood group AB.
4. Blood group O: has neither A nor B agglutinogens in the
plasma. The % is 45. This group is called Universal Donor (a donor gives blood). Blood group O gives blood to all but can't receive blood except from person of blood group O.


Table: blood groups their agglutinogens, agglutinins , and %.
Blood group
Agglutinogens
Agglutinins
%

O
-
Anti-A, Anti-B
45
Universal donor
A
A
Anti-B
41

B
B
Anti-A
10


AB
A,B
-
4
Universal recipient

ABO Transfusion Reactions

Transfusion: is the transfer of blood or other solutions from the donor into the blood of patient (or recipient). Transfusion reaction or agglutination (clumping): is the reaction between agglutinogens on the donor's red blood cells and agglutinins in the recipient's plasma. Dangerous hemolytic transfusion recipients occur when blood of donor transfused into an individual with an incompatible blood type. For example a person with type A blood would denote to another person with type A blood because there would be no ABO transfusion reaction, the recipient has no antibodies against the type A antigens. Also person with type A can give blood to a person with type AB and no agglutination. Blood group A can receive blood only from type A and O.
On the other hand if type A blood is donated to a person with type B, there would be a transfusion reaction because the person with type B blood has agglutinins against type A-agglutinogens and agglutination would result.
Person with type O are called “universal donor” can be given to anyone without producing a serious transfusion reaction due to ABO incompatibility, because they lack antigens A&B. for example if type O blood is given to a person with type A or type B blood, the type O erythrocytes don not react with type B antibodies or type A antibodies respectively in the recipient’s blood.
Person with type AB blood are called “universal recipient” because they have no circulating agglutinins & can give blood of any type without developing a serous transfusion reaction. Type AB blood does not have antibodies against A or B antigens. Therefore type AB blood could receive blood for any type of blood without developing transfusion reaction. The clumping of RBC s is occurred by the following process: the binding sites of agglutinins can attach to more than two RBC’s at the same time there by causing the cells to adhere to each other. As a result clumping of RBC’s occurs. Then these clumps plug small blood vessels & hemolysis of cells occurs, Hb is liberated into the plasma & the level of bilirubin rise and renal damage with anuria and death. So one of he most lethal effects of transfusion reaction is kidney shutdown and the person dies of renal failure.

Table 2 shows the compatibility & incompatibility between donors & recipients blood transfusion.
Table 2: The compatibility & incompatibility between donors & recipients blood transfusion.

Donor

Type A

Type B

Type AB

Type O

Recipient
Type A

-

+

+

-

Type B

+

-


+

-

Type AB

-

-

-

-

Type O

+

+

+


-

- No agglutination

+ Agglutination

Indications for Transfusion:

The most common reason for transfusion is decreased blood volume.
Treating anemia or to supply the recipient with some other constituent of whole blood besides red blood cells, such as to supply a thrombocytopenic patient with new platelet
Hemophilic patients can be rendered temporarily non-hemophilic by plasma transfusion.

Lec.11 ,12 26, Nov 2017
2. Rh-Blood Group

Objectives:

Rh Blood Type
Rh transfusion reaction
Rh-Blood groups: Another important blood group is the Rh-system is also important in the transfusion of blood. The Rh-factor named for the rhesus monkey because it was first studied using the blood of this animal.

Rh-agglutinogens:: there are six common types of Rh-antigens each of which is called Rh-factor. These types are C, D, E, c, d, & e.The type D (Rh)-antigen is widely prevalent in the population. Therefore anyone who has this type of antigen on RBC membrane is said to be Rh-positive (Rh+) or D-positive (D+) about 85% of population are Rh+, while persons who does not have antigen D on their RBC is said to be Rh-negative (Rh-) or D- & about 15% are D- (Rh-). Rh+ is dominant while Rh- is ressive.


Rh-agglutinins: The Rh+ individual has no antibody in their plasma. The Rh- person has also no antibody D in the plasma, but Rh- individual forms the antibody –D when injected with D+ (Rh+) cells. Antibodies against Rh-antigen do not develop unless an Rh- person is exposed to Rh+- blood. This can occur through a transfusion or entrance of fetal blood into the maternal circulation across the placenta.
Table 3 demonstrates Rh –type, agglutiongen, agglutinin, and % of each Rh –group.

Table 3: Rh –type, agglutiongen, agglutinin, and % of each

Rh group.

Rh-type

Agglutinogen on RBC
Agglutinins in plasma
%
Rh+
D
--
85
Rh-
--
--
15

The ABO blood type & the Rh -blood type usually are designated together.

(ABO-system) (Rh-system).
For example a person designated as A positive (A+) is blood group A in the ABO- system and Rh+ in the Rh blood group. This person has antigens A & D on RBC & antibody-B& no antibody-D in the plasma.


Rh –Transfusion Reaction
Example: Hemolytic disease of newborn (HDN) or erythroblastosis fetalis.Fetus may develop hemolytic anemia in two major ways a consequence of developing antibodies.
1. Rh- incompatibility.
2. ABO- incompatibility

A.HDN due to Rh-incompatibility

Rh –Transfusion Reaction: is the reaction between antigen -D in Rh+ blood of donor & antibody D in Rh- blood of recipient. When an Rh- receives a first transfusion of Rh+ blood, the recipient becomes sensitized to the Rh+ antigen & produces antibodies D. If the same person is unfortunate receive a second transfusion of Rh+ blood, reactions results & clumping of RBC’s occurs.
Hemolytic disease of newborn (HDN) or erythroblastosis fetalis:HDN: is a disease of he fetus & neonate characterized by agglutination between antigen D in the fetus & antibody D produce by the mother can pose a major problem in some pregnancies when the mother is Rh- antigen ,the father is Rh+ and fetus is Rh The baby has inherited the Rh + antigen from the father i.e. if an Rh- female marries an Rh+ male, she has 50% of producing an Rh+ fetus if father is heterozygous (Rh+Rh-).
Mother Rh- (Rh- Rh -) X father+ (Rh+ Rh-) heterozygous
Fetus : 50% Rh+ (Rh+ Rh-) , 50%Rh – (Rh – Rh –)

A 100% chance of producing an Rh+ fetus if the father is homozygous (Rh+ Rh+).

Mother (Rh- Rh-) X father (Rh+ Rh+) homozygous

Fetus: 100% Rh+ Rh-

During pregnancy the maternal & fetal circulation are separate. At the time of delivery small amount of fetal blood which contain antigen D leak into the maternal circulation & some mother develop antibody D during postpartum period. In the woman’s first pregnancy there is no problem. The leakage of fetal blood which contain antigen D is usually the result of a tear in the placenta that takes place during delivery. Thus there is no enough time for the mother to produce enough to form D- antibodies to harm the fetus. In the later pregnancies, a problem can arise because the mother has been sensitized (i.e. forming antibody-D) against antigen D in the fetus. When the mother becomes pregnant again with another Rh+ fetus, and if there is any leakage of fetal blood into the mother’s blood through the placenta she rapidly produce large amounts of Rh-antibodies & HDN develops in the fetus. The term erythroblastosis fetalis is also used to describe HDN since blood smears from these babies show the presence of many immature red blood cells or erythroblasts.

Figure 1:hemolytic disease of newborn(HDN).

Prevalence of disease: an Rh negative mother having her first Rh –positive child usually does not develop sufficient anti – D to cause any harm. About 3% of second Rh –positive babies exhibit some signs of HDN; 17% of the third babies exhibit the disease; and the incidence rises progressively with subsequent pregnancies. About 50% of Rh negative individuals are sensitized (develop an anti-Rh titer) by transfusion of Rh+ blood.

Symptoms of disease:

1. severe jaundice 2. Odema (hyrops fetalis).
3. Kernicterus due to deposition of bilirubin in the basal ganglia which result in brain damage & mental retardation. 4. Splenomegaly & hepatomegaly (i.e. enlargement of spleen & liver).

Treatment of HDN

1.Treatment of mother: The Rh- woman should be given an injection of single dose of anti-D antibodies which is called Rho(D) immune globulin (RhoGAM) within 72 hours during the postpartum period or during pregnancy or immediately after each abortion. The injection contains anti-D against antigen-D.The injected antibodies will bind to
Rh – antigens of fetus erythrocytes that may have entered the mother's blood and destroy the antigen D on fetal RBC before the immune system of the mother is activated. In other words, the fetal RBC s will be destroyed before the mother is able to develop her own antibodies against these erythrocytes. Hence she will be able to conceive another Rh+ child without any complication.

2.Treatment of erythroblastic neonate: 1. By exchange transfusion i.e. slowly removing the newborn’s blood & replacing it with Rh—blood to reduces the level of maternal antibody-D, which thereby decreases the level of fetal RBC hemolysis. 2. Exposure of newborn to fluorescent light to breakdown the large amount of bilirubin formed as a result of erythrocyte destruction. High levels of bilirubin are toxic to the nervous system and can damage brain tissues.3.In addition fetal Rh-typing with obtained material by amniocentesis or choronic villus sampling is now possible and treatment with a small dose of Rh immune serum will prevent sensitization during pregnancy.

B. HDN due to ABO-incompatibility: when a mother of type O blood becomes pregnant & the fetus has type A or B antigens on RBC this may result in anemia known as HDN. The ABO-HDN is the more common that Rh-HDN. Approximately 23% of all pregnancies involve incompatible ABO system.Blood