The Story of Blood Group Discovery Submitted by Abdul Nasser Kaadan, md, PhD

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The Story of Blood Group Discovery




Submitted by

Abdul Nasser Kaadan, MD, PhD*

** Muhammad Alkhatib

Contents:

- Introduction

- Definition:

- ABO Blood Grouping System

- Rh Factor Blood Grouping System

- Blood Group Notation

- Antigens and Antibodies

- Importance of The ABO System

- Indications for The ABO Grouping

- Dicovery of The ABO System

- ABO Typing

- Characteristics of ABO Antigens

- Characteristics of ABO Antibodies

- ABO Inheritance

- Biochemistry of The ABO System

- Rarest Blood Type:

- Rarest Blood Type in Humans

- Rarest Blood Type in The World

- Early Practices

- Blood Banks

- Clinical Trials

- New Hemoglubin Type Found

- Blood Type Discovery May Lead To New Tools In

HIV Fight

Biography:

- Karl Landsteiner

- Emil Fischer

- James Blundelle

- William Harvey

- Jan Jansky

Introduction:

An adult human has about 4–6 liters of blood circulating in the body. Among other things, blood transports oxygen to various parts of the body. Blood consists of several types of cells floatingaround in a fluid called plasma.

The red blood cells contain hemoglobin, a protein that binds oxygen. Red blood cells transport oxygen to, and remove carbon dioxide from, the body tissues.

The white blood cells fight infection.

The platelets help the blood to clot, if you get a wound for example.

The plasma contains salts and various kinds of proteins.



Definition:

The differences in human blood are due to the presence or absence of certain protein molecules called antigens and antibodies. The antigens are located on the surface of the red blood cells and the antibodies are in the blood plasma. Individuals have different types and combinations of these molecules. The blood group you belong to depends on what you have inherited from your parents.



There are more than 20 genetically determined blood group systems known today, but the AB0 and Rh systems are the most important ones used for blood transfusions. Not all blood groups are compatible with each other. Mixing incompatible blood groups leads to blood clumping or agglutination, which is dangerous for individuals.
AB0 blood grouping system

According to the AB0 blood group system there are four different kinds of blood groups: A, B, AB or 0 (null).





Blood group A

If you belong to the blood group A, you have A antigens on the surface of your red blood cells and B antibodies in your blood plasma.




Blood group B

If you belong to the blood group B, you have B antigens on the surface of your red blood cells and A antibodies in your blood plasma.





Blood group AB

If you belong to the blood group AB, you have both A and B antigens on the surface of your red blood cells and no A or B antibodies at all in your blood plasma.





Blood group 0

If you belong to the blood group 0 (null), you have neither A or B antigens on the surface of your red blood cells but you have both A and B antibodies in your blood plasma.




Rh factor blood grouping system







 

Many people also have a so called Rh factor on the red blood cell's surface. This is also an antigen and those who have it are called Rh+. Those who haven't are called Rh-. A person with Rh- blood does not have Rh antibodies naturally in the blood plasma (as one can have A or B antibodies, for instance). But a person with Rh- blood can develop Rh antibodies in the blood plasma if he or she receives blood from a person with Rh+ blood, whose Rh antigens can trigger the production of Rh antibodies. A person with Rh+ blood can receive blood from a person with Rh- blood without any problems.



Blood group notation:

According to above blood grouping systems, you can belong to either of following 8 blood groups:




A Rh+

B Rh+

AB Rh+

0 Rh+

A Rh-

B Rh-

AB Rh-

0 Rh-

 

Blood typing:

how do you find out to which blood group soeone belongs?

 1.
You mix the blood with three different reagents including either of the three different antibodies, A, B or Rh antibodies.

2.
Then you take a look at what has happened. In which mixtures has agglutination occurred? The agglutination indicates that the blood has reacted with a certain antibody and therefore is not compatible with blood containing that kind of antibody. If the blood does not agglutinate, it indicates that the blood does not have the antigens binding the special antibody in the reagent.

3.
If you know which antigens are in the person's blood, it's easy to figure out which blood group he or she belongs to!








What happens when blood clumps or agglutinates?

For a blood transfusion to be successful, AB0 and Rh blood groups must be compatible between the donor blood and the patient blood. If they are not, the red blood cells from the donated blood will clump or agglutinate. The agglutinated red cells can clog blood vessels and stop the circulation of the blood to various parts of the body. The agglutinated red blood cells also crack and its contents leak out in the body. The red blood cells contain hemoglobin which becomes toxic when outside the cell. This can have fatal consequences for the patient.The A antigen and the A antibodies can bind to each other in the same way that the B antigens can bind to the B antibodies. This is what would happen if, for instance, a B blood person receives blood from an A blood person. The red blood cells will be linked together, like bunches of grapes, by the antibodies. As mentioned earlier, this clumping could lead to death.

Blood transfusions: who can receive blood from whom?

Of course you can always give A blood to persons with blood group A, B blood to a person with blood group B and so on. But in some cases you can receive blood with another type of blood group, or donate blood to a person with another kind of blood group.


The transfusion will work if a person who is going to receive blood has a blood group that doesn't have any antibodies against the donor blood's antigens. But if a person who is going to receive blood has antibodies matching the donor blood's antigens, the red blood cells in the donated blood will clump.


People with blood group 0 Rh - are called "universal donors" and people with blood group AB Rh+ are called "universal receivers."
Rh+ blood can never be given to someone with Rh - blood, but the other way around works. For example, 0 Rh+ bloodcan not be given to someone with the blood type AB Rh -.

Blood Group

Antigens

Antibodies

Can give blood to

Can receive blood from

AB Rh+

A, B and Rh

None

AB Rh+

AB Rh+

AB Rh -

A Rh+
A Rh -
B Rh+
B Rh -
0 Rh+
0 Rh -


AB Rh -

A and B

None
(Can develop Rh antibodies)

AB Rh -
AB Rh+

AB Rh -
A Rh -
B Rh -
0 Rh -

A Rh+

A and Rh

B

A Rh+
AB Rh+

A Rh+
A Rh -
0 Rh+
0 Rh -

A Rh -

A

B
(Can develop Rh antibodies)

A Rh -
A Rh+
AB Rh -
AB Rh+

A Rh -
0 Rh -

B Rh+

B and Rh

A

B Rh+
AB Rh+

B Rh+
B Rh -
0 Rh+
0 Rh-

B Rh -

B

A

(Can develop Rh antibodies)


B Rh-
B Rh+
AB Rh-
AB Rh+

B Rh -
0 Rh -

0 Rh+

Rh

A and B

0 Rh+
A Rh+
B Rh+
AB Rh+



0 Rh+
0 Rh -

0 Rh -

None

A and B (Can develop Rh antibodies)

AB Rh+
AB Rh -
A Rh+
A Rh -
B Rh+
B Rh -
0 Rh+
0 Rh -

0 Rh -






Type

You Can Give Blood To

You Can Receive Blood From

A+

A+  AB+

A+  A-  O+  O-

O+

O+  A+  B+  AB+

O+  O-

B+

B+  AB+


B+  B-  O+  O-

AB+

AB+

Everyone

A-

A+  A-  AB+  AB-

A-  O-

O-

Everyone

O-

B-

B+  B-  AB+  AB-

B-  O-

AB-

AB+  AB-

AB-  A-  B-  O-










Blood donation possibilities
ANTIGENS AND ANTIBODIES



Blood group system

A series of antigens exhibiting similar serological and physiological characteristics, and inherited according to a specific pattern.

Importance of the ABO system:

This is the only blood group system in which antibodies are consistently, predictably, and naturally present in the serum of people who lack the antigen. Therefore  ABO compatibility between donor and recipient is crucial since these strong, naturally occurring A and B antibodies are IgM and can readily activate complement and cause agglutination.  If ABO antibodies react with antigens in vivo, result is acute hemolysis and possibly death.


Indications for ABO grouping:

ABO grouping is required for all of the following individuals:


  • Blood Donors:since it can be life threatening to give the wrong ABO group to the patient.

  • Transfusion recipients: since we need to know the donor blood is ABO compatible.

  • Transplant Candidates and Donors: ABO antigens are found in other tissues as well.  Therefore the transplant candidates and donors must be compatible.

  • Prenatal Patients: To determine whether the mothers may have babies who are suffering from ABO-HDN.  It is also beneficial to know the ABO group should she start hemorrhaging.

  • Newborns: If the baby is demonstrating symptoms of Hemolytic Disease of the Newborn, the ABO group needs to be determined along with Rh and others.

  • Paternity testing:Since the inheritance of the ABO Blood Group System is very specific, this serves as one of the first methods to determine the likelihood that the accused father is the father or not.

Discovery of the ABO system:

In 1900 Karl Landsteiner reported a series of tests, which identified the ABO Blood Group System.  In 1910 he won Nobel prize for medicine for this discovery.  He mixed the serum and cells of all the researchers in his lab and found four different patterns of agglutination.  From those studies he developed what we now know as Landsteiner's rules:



  1. A person does not have antibody to his own antigens

  2. Each person has antibody to the antigen he lacks (only in the ABO system)

Incidence (%)  of ABO Blood Groups in the US Population

ABO Group

Whites

Blacks

O


45

49

A

40

27

B

11

20

AB

4

4

ABO Typing

ABO typing involves both antigen typing and antibody detection.  The antigen typing is referred to as the forward typing and the antibody detection is the reverse typing



  • The forward typing determines antigens on patient's or donor's cells
    a. Cells are tested with the antisera reagents anti-A, anti-B, (and in the case of donor cells anti-A,B)
    b. Reagents are either made from hyperimmunized human sources, or monoclonal antibodies. 
    c. One advantages of the monoclonal antibodies are the antibody strength.
    d. Another advantage of monoclonals: human source reagents can transmit infectious disease (hepatitis).

  • Reverse typing  determines antibodies in patient's or donor's serum or plasma
    a. Serum tested with reagent A1 cells and B cells
    b. Reverse grouping is also known as backtyping or serum confirmation

Routine ABO Typing

Reaction of Cells Tested With

Red Cell ABO Group


Reaction of Serum Tested Against

Reverse ABO Group

Anti-A

Anti-B

 

A1 Cells

B Cells

 

0

0

O

+

+

O

+

0

A

0

+

A

0

+

B

+

0

B

+

+

AB

0

0

AB

Discrepancies in ABO typing

  1. Results of forward and reverse typing must agree before reporting out blood type as seen in the about table.

  2. If forward and reverse do not agree, must identify cause of discrepancy.

  3. If cannot resolve discrepancy, must report out blood type as UNKNOWN and give group O blood

Characteristics of ABO antigens:

ABO antigens are glycolipid in nature, meaning they are oligosaccharides attached directly to lipids on red cell membrane.  These antigens stick out from red cell membrane and there are  many antigen sites per red blood cell (approximately 800,000)

Besides their presence on red blood cells, soluble antigens can be present in plasma, saliva, and other secretions.  These antigens are also  expressed on tissues other than red cells.  This last fact is important to consider in organ transplantation.

ABO antigens are  only moderately well developed at birth.  Therefore ABO-HDN not as severe as other kinds of Hemolytic Disease of the Newborn.


Characteristics of ABO antibodies:


  1. These are expected naturally occurring antibodies that occur without exposure to red cells containing the antigen.  (There is some evidence that similar antigens found in certain bacteria, like E.coli, stimulate antibody production in individuals who lack the specific A and B antigens.)

  2. Immunoglobulin M antibodies, predominantly

  3. They react in saline and readily agglutinate. Due to the position of the antigen and the IgM antibodies it is not necessary to overcome the zeta potential.

  4. Their optimum temperature is less than 30oC, but reactions do take place at body temperature

  5. Not only are these antibodies expected and naturally occurring, they are also commonly present in high titer, 1/128 or 1/256.

  6. They are absent at birth and  start to appear around 3-6 months as result of stimulus by bacterial polysaccharides.  (For this reason, newborn blood is only forward typed.)

ABO INHERITANCE

Inheritance Terminology:

gene: determines specific inherited trait (ex. blood type)

chromosome: unit of inheritance. Carries genes.23 pairs of chromosomes per person, carrying many genes. One chromosome inherited from mother, one from father

locus: site on chromosome where specific gene is located

allele: alternate choice of genes at a locus (ex. A or B; C or c, Lewis a or Lewis b)

homozygous: alleles are the same for any given trait on both chromosome (ex. A/A)

heterozygous: alleles for a given trait are different on each chromosome (ex. A/B or A/O)

phenotype: observed inherited trait (ex. group A or Rh positive)

genotype: actual genetic information for a trait carried on each chromosome (ex. O/O or A/O)

dominant: the expressed characteristic on one chromosome takes precedence over the characteristic determined on the other chromosome (ex. A/O types as A)

co-dominant: the characteristics determined by the genes on both chromosomes are both expressed - neither is dominant over the other (ex. A/B types as AB)

recessive: the characteristic determined by the allele will only be expressed if the same allele is on the other chromosome also (ex. can type as O only when genotype is O/O)





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