Blood Groups & Physiological

Basis of Blood Transfusion

Dr Athira S B
Tutor
Department of Physiology
AIIMS, Patna
Learning Objectives
The student MUST be able to:
➢Understand blood groups, classification and give the physiological basis of
blood grouping
➢Describe the agglutinogens, agglutinins in ABO system, and understand
the mechanism of inheritance of ABO blood groups
➢ Define Landsteiner’s law and give its physiological basis
➢Describe the antigens and antibodies in Rh system, and the mechanism of
Rh incompatibility
➢Erythroblastosis fetalis- etiology, features, physiological basis of treatment
and prevention
➢Concept of universal donor, universal recipient, and major and minor cross
matching
 BLOOD GROUPS
• Red cell surface contain structures recognized by the immune system -
blood group antigens/agglutinogens
• Blood grouping is based on the presence or absence of inherited antigens
on the surface of RBCs
• These antigens may be proteins, carbohydrates, glycoproteins, or
glycolipids, depending on the blood group system.
• There are more than 30 commonly occurring antigens and hundreds of
rare antigens found on the surface on RBCs which can cause antigen-
antibody reactions
• Two particular types of antigens- A-B-O system of antigens and the Rh
system are more important as they can cause blood transfusion reactions.
A-B-O BLOOD GROUP SYSTEM
• Karl Landsteiner discovered the ABO Blood Group
System in 1901, for which he was given the Nobel Prize
for Physiology or Medicine in 1930.

• He classified human beings into 4 groups: A,B,AB & O

depending on certain antigens present on red cells

• In 1927, Landsteiner & Levine found another blood

group system comprising of M,N & MN

• In 1940, Landsteiner & Weiner discovered Rh factor

• Other blood group systems - MNS, Lewis, Duffy, Kell, P

and Lutheran systems
A-B-O SYSTEM & AGGLUTINOGENS
• This is the most important system in transfusion medicine

• Individuals are divided into 4 blood groups in this system- A,B,AB,O blood groups
based on 2 antigens/agglutinogens - A&B

Group A – Antigen A

Group B – Antigen B

Group AB – Antigen A,B

Group O – Nil

• A antigen has two sub-types- A and A1

• The genes for antigens for ABO system are AB genes, located on chromosome 9.

• Agglutinogens are also found in tissues like salivary glands, saliva, pancreas,
kidney, liver, lungs, testes, semen & amniotic fluid
Time of Appearance:
• ABO antigens appear in fetal life, first appearing at the sixth week.
• They reach a concentration of one-fifth in adults at birth, increasing slowly to
a significant level at puberty and reaching maximum at 15-17 years of age

Distribution
• In the Indian population, the approximate distribution of the ABO blood
group :
O : 34%
B : 31%
A : 27% (A1 is 75% and A2 is 25%)
AB : 8%
STRUCTURE OF A & B ANTIGENS - Complex oligosaccharides, differ in
their terminal sugars on H Antigen
ABO Agglutinins
• There are two types of agglutinins : anti-A (α) and anti-B (β), present in the serum
• They are antibodies (gamma globulins) against red cell antigens
• Most of them are IgM and IgG immunoglobulin
• Produced by the bone marrow and lymph gland cells
• They act best at low temperature - cold antibody (5-20oC)
Time and Mechanism of Appearance:
• Anti-A and anti-B agglutinins are not formed during fetal life and are absent at
birth
• Two to 8 months after birth, infant begins to produce agglutinins (antigens similar
to A&B are present in intestinal bacteria & food which develops of Anti A & Anti B
agglutinins).
• Maximum level is reached at 8-10 years & gradually declines
ABO Agglutinins
• Antibodies are directed against the antigens
• When type A agglutinogen is present in a person's red blood cells, anti-A
antibodies will be absent in the plasma.
• Similarly, if type B agglutinogen is present, anti-B antibodies will be absent
in the plasma
Landsteiner’s law

1. If an agglutinogen is present on the red cell membrane of

an individual, the corresponding agglutinin must be

absent in his plasma

2. If the agglutinogen is absent in the red cells, the

corresponding agglutinin must be present in the plasma

Inheritance of ABO Blood Groups
• Inherited as Mendelian dominants
• The A-B-O blood type is determined by two
genes, one on each of the paired
chromosomes
• These genes can be type O, type A, or type B,
with only one type present on each
chromosome.
• The type O gene is nearly functionless,
producing no significant agglutinogen on the
cells
• The type A and type B genes create strong
agglutinogens
Inheritance of
ABO antigen
Agglutination

• When bloods are mismatched- anti-A or anti-B plasma

antibodies are mixed with red blood cells contains A or B agglutinogens

• The reaction between blood group antigens & corresponding antibody

causing them to clump together - agglutination

• Antibodies can bind to multiple red cells (with IgG having 2 binding sites
and IgM having 10)

• These agglutinated cells are either physically damaged or destroyed by

white blood cells, releasing hemoglobin into the plasma- hemolysis
Rh System
• First described in Rhesus monkeys in 1940 -
Rh System

• Six common types of Rh antigens/Rh factor-

C, D, E, c, d, and e

• Most antigenic & widely prevalent - D

antigen

• Rh+ve: with D antigen

• Rh-ve: with no D antigen

Inheritance of Rh antigen

• Rh antigen is inherited as dominant gene

• Rh antigens determined by 3 pairs of allelic genes ( Cc, Dd, Ee)
• Rh +ve individual may have homozygous (DD) or heterozygous (Dd)
genotypes and the genotype of Rh –ve person is dd

Inheritance of Rh antigen
Rh Antibody

• Anti-D antibody- produced only when an Rh negative individual

receives the Rh positive blood

• Ig G type, which can cross placental barrier

• Rh antibody is best reactive at body temperature - warm

antibody
 Differences – ABO and Rh system

• Unlike ABO antigens, Rh antigens has not been detected in

tissues other than red cells

• Unlike the antibodies of ABO system, the antibodies of Rh

system do not develop spontaneously
Rh Incompatibility- It occurs when an Rh negative individual receives
Rh positive blood
When Rh-ve person is exposed to Rh+ve blood
↓
IgG anti Rh agglutinins (develop slowly, reaching maximum concentration 2 to 4
months)
↓
Donor’s red cells die and the anti-Rh antibody cannot produce any harm to the recipient’s
red cells
↓
If the same Rh negative person, receives a second
Rh positive transfusion later
↓
Anti-Rh antibodies are synthesized in large amount immediately by the
memory cells
↓
Hemolysis
Erythroblastosis Fetalis
• Hemolytic disease of the newborn
• Rh negative mother carries Rh positive fetus
• IgG antibody usually produced after mixing of blood during delivery at the
time of placental separation
• 1st Rh positive fetus usually unaffected
• 2nd Rh positive fetus affected and cause hemolysis, IgG can cross
placenta
• Incidence rises progressively with subsequent pregnancies
• At birth, excessive destruction of RBCs is compensated by an intense
normoblastic response of the marrow
• High reticulocyte count and mature nucleated blast forms in circulation -
erythroblastosis fetalis
Clinical Features
Severe hemolysis - the fetus may die in utero

• Anemia

• Extramedullary hemopoiesis

• Hemolytic jaundice

• Neonatal hyperbilirubinemia

• Generalized edema - Hydrops fetalis

• Kernicterus: Neurologic syndrome with major motor deficits due to the

deposition of bilirubin in the basal ganglia
Treatment
• Intrauterine fetal transfusion
• Exchange transfusion- Small quantities of the infant’s blood are withdrawn
& replaced by Rh-ve blood

• Phototherapy

Preventive measures
Anti D immunoglobulin- Anti D antibody is administered to Rh negative
women who deliver Rh positive babies
These antibodies attach to D antigen sites on Rh positive fetal RBCs and
decreases immune response to D antigen by mother’s body
 Blood Grouping
• Blood cells are allowed to react with the
sera containing known agglutinins

• When a drop of anti-serum is mixed with

a blood sample, agglutination (clumping)
will occur if the corresponding antigen is
present on the red blood cells.
A+

B+

AB+

O-
Importance of blood groups

• To prevent mismatched blood transfusion and organ transplantation

• To solve disputed paternity cases

• Medicolegal importance

• In pregnancy to avoid Rh incompatibility

 Blood Transfusion

Process of transferring blood or blood components from one person (donor)

into bloodstream of another person (recipient)
Indications for Transfusion
➢Acute blood loss
➢Anemia
➢Bone marrow failure
➢Purpura
➢Clotting factor deficiencies
➢Surgery
➢Burns
Ideal Donor

• Healthy, 18-60 years

• Normal BP
• Weight > 45kg
• Hemoglobin normal
• Minimum interval between 2 donations- 3 months
• No infective diseases, no chronic medications
• Same blood group & Rh type
 Blood Typing
• Two major blood group systems for transfusion - ABO and Rh systems

• Universal Donor- O negative

• Universal Recipient- AB positive

Only when blood of same group is not available

Cross-matching

Major Cross-matching: The cells of the donor (donor’s agglutinogen) are

directly matched against the plasma of the recipient (recipient’s agglutinin)

To ensure that antibodies present in the recipient’s plasma do not harm the
donor’s red cells

Minor Cross-matching: The donor’s plasma is checked against the red cells
of the recipient

Plasma of the donor is highly diluted with recipient’s plasma. So the effects
of antibodies in donor plasma on the recipient cells are negligible
Collection & Storage of blood

• About 400 - 450 ml of blood is collected at a time

• Collected from antecubital vein

• Stored in sterile polyvinyl chloride blood bags containing a measured

quantity of anticoagulant (Acid Citrate Dextrose, Citrate Phosphate
Dextrose, Citrate Phosphate Dextrose Adenine)

• It is stored at 4o C

• Should ideally be used within 2 weeks of storage

Hazards of Blood Transfusion

I. Due to Mismatched Transfusion - agglutination of donor’s red cells

followed by their hemolysis. The complications of mismatched
transfusion are:

1. Shivering and fever (febrile reactions) occur usually

2. Hemoglobinemia and hemoglobinuria

3. Hemolytic jaundice

4. Acute renal failure

5. Hyperkalemia
II. Due to Faulty Techniques of Giving Blood: Due to wrong method of
transfusion. Complications are Thrombophlebitis, Air Embolism

III. Due to Massive Transfusion: when more than 10 units of blood are given
within 24 hours- circulatory overload

IV. Febrile Reaction: The patient feels cold and may get rigor due to rise in
body temperature

V. Allergic Reactions

VI. Transmission of Diseases such as Hepatitis, Malaria, AIDS and Syphilis