Introduction
- Blood groups are determined by the presence or absence of specific antigens on the surface of red blood cells (RBCs).
- These antigens are genetically inherited from our parents.
There are more than 30 blood group systems, but the most clinically important are:
ABO blood group system
Rhesus (Rh) factor system
These systems are important in blood transfusion, organ transplantation, and pregnancy.
ABO Blood Group System
Discovery
Discovered by Karl Landsteiner in 1901.
He found that mixing blood from different individuals sometimes caused clumping (agglutination), which led to the identification of A, B, AB, and O blood groups.
Genetic Basis
The ABO gene is located on chromosome number 9 (9q34).
This gene has three alleles: IA, IB, and i.
IA → produces A antigen on the red cell surface.
IB → produces B antigen on the red cell surface.
i → produces no antigen.
Dominance Relationship:
IA and IB are co-dominant, meaning both can be expressed together.
i is recessive, meaning it will be expressed only when both alleles are i (ii).
Molecular Basis of ABO System
The A and B antigens are complex sugar molecules (oligosaccharides) present on the surface of RBCs.
The H antigen acts as the base structure.
The A allele codes for an enzyme that adds N-acetylgalactosamine to the H antigen.
The B allele codes for an enzyme that adds galactose to the H antigen.
The O allele produces no enzyme, so the H antigen remains unchanged.
Thus:
| Blood Type | Antigen on RBC | Added Sugar Molecule |
|---|---|---|
| A | A antigen | N-acetylgalactosamine |
| B | B antigen | Galactose |
| AB | A and B antigens | Both sugars |
| O | No antigen | None |
Genotypes and Phenotypes
| Blood Group | Genotype | Antigen on RBC | Antibody in Plasma |
|---|---|---|---|
| A | IAIA or IAi | A antigen | Anti-B |
| B | IBIB or IBi | B antigen | Anti-A |
| AB | IAIB | A and B antigens | None |
| O | ii | None | Anti-A and Anti-B |
Inheritance Pattern
Each individual inherits one allele from each parent.
Examples:
| Parents’ Blood Groups | Possible Blood Groups of Children |
|---|---|
| A × A | A or O |
| A × B | A, B, AB, or O |
| A × O | A or O |
| B × O | B or O |
| AB × O | A or B |
| AB × AB | A, B, or AB (no O) |
Possible Blood Types
There are four main blood types based on ABO grouping:
A type – has A antigen and anti-B antibodies
B type – has B antigen and anti-A antibodies
AB type – has both A and B antigens; no antibodies
O type – has no antigens; both anti-A and anti-B antibodies
Blood Type Compatibility
Blood Transfusion Principles
Antigen-antibody reaction is the key.
If mismatched blood is transfused, agglutination (clumping) and hemolysis occur, which can be fatal.
| Recipient’s Blood Type | Can Receive Blood From | Can Donate Blood To |
|---|---|---|
| A | A, O | A, AB |
| B | B, O | B, AB |
| AB | A, B, AB, O | AB (universal recipient) |
| O | O only | A, B, AB, O (universal donor) |
Explanation:
O blood group has no antigens → safe for all recipients.
AB blood group has no antibodies → can receive from all groups.
ABO Blood Group and Associated Health Risks
Research studies show some correlations between blood groups and diseases:
| Blood Group | Health Associations |
|---|---|
| A | Higher risk of stomach and pancreatic cancers, heart disease, and severe COVID-19 infection. |
| B | Slightly increased risk of diabetes and blood clotting disorders. |
| AB | Higher risk of cognitive impairment and thrombosis. |
| O | Lower risk of heart disease and cancer, but higher risk of peptic ulcer due to H. pylori. |
Note: These are associations, not direct causes.
Rhesus (Rh) Factor
The Rhesus (Rh) blood group system is one of the most important blood group systems after the ABO system.
It was discovered in 1940 by Karl Landsteiner and Alexander Wiener while studying Rhesus monkeys, hence the name Rhesus factor.
The Rh system is based on the presence or absence of a specific antigen known as the D antigen on the surface of red blood cells (RBCs).
Types of Rh Factor
Rh Positive (Rh⁺)
If D antigen is present on RBCs.
Example: Blood type A⁺, B⁺, AB⁺, or O⁺.
Rh Negative (Rh⁻)
If D antigen is absent on RBCs.
Example: Blood type A⁻, B⁻, AB⁻, or O⁻.
Approximately 85% of people are Rh positive, while 15% are Rh negative.
Genetic Basis
The Rh factor is controlled by a gene located on chromosome number 1.
The gene has two main alleles:
D (dominant) – produces the Rh (D) antigen.
d (recessive) – produces no antigen.
Genotypes and Phenotypes
| Genotype | Phenotype | Description |
|---|---|---|
| DD | Rh⁺ | Homozygous dominant |
| Dd | Rh⁺ | Heterozygous |
| dd | Rh⁻ | Homozygous recessive |
Inheritance:
Each person inherits one Rh gene from each parent.
Example:
If both parents are Rh⁺ (Dd), their child can be Rh⁺ or Rh⁻ depending on the combination of alleles.
Rhesus Factor and Blood Transfusion
Compatibility Rules:
| Recipient’s Rh Type | Can Receive Blood From | Cannot Receive Blood From |
|---|---|---|
| Rh⁺ | Rh⁺, Rh⁻ | — |
| Rh⁻ | Rh⁻ only | Rh⁺ (causes reaction) |
If an Rh⁻ person receives Rh⁺ blood, the immune system recognizes the D antigen as foreign and produces anti-D antibodies.
On second exposure, these antibodies attack and destroy the Rh⁺ red cells → causing hemolytic transfusion reaction.
Rhesus Factor and Pregnancy
Rh Incompatibility
Occurs when:
Mother → Rh⁻
Father → Rh⁺
Baby → Rh⁺ (inherits D antigen from the father)
During pregnancy or delivery, some fetal Rh⁺ blood may enter the mother’s bloodstream.
This causes the mother’s immune system to form anti-D antibodies (sensitization).
Effect on Future Pregnancies
In the first pregnancy, usually no problem occurs because antibodies form slowly.
In the next pregnancy with another Rh⁺ baby, the mother’s anti-D antibodies can cross the placenta and destroy the baby’s red blood cells.
This condition is called Hemolytic Disease of the Newborn (HDN) or Erythroblastosis Fetalis.
Symptoms of HDN
Severe anemia in the baby
Jaundice (yellow skin and eyes)
Enlarged liver and spleen
Swelling (edema)
In severe cases → stillbirth or death of the baby
Prevention
Anti-D Immunoglobulin (Rho(D) Injection)
Given to Rh⁻ mothers within 72 hours after delivery of an Rh⁺ baby.
Also given after miscarriage, abortion, or ectopic pregnancy.
It destroys any Rh⁺ fetal cells in the mother’s blood before her immune system can react.
Blood Typing During Pregnancy
Both parents’ blood groups are tested early in pregnancy to assess the risk.
Monitoring
Antibody screening and fetal health checks (ultrasound, amniotic fluid tests) are done regularly if incompatibility is suspected.
Clinical Importance of Rh Factor
Safe Blood Transfusion – prevents hemolytic reactions.
Safe Pregnancy – avoids HDN by giving anti-D injection.
Blood Donation and Organ Transplantation – ensures compatibility.
Forensic Medicine – helps in parentage testing and identity verification.
Genetic Basis
Controlled by RhD gene on chromosome 1.
Two main alleles:
D (dominant) → produces D antigen (Rh⁺)
d (recessive) → no antigen (Rh⁻)
Genotypes:
DD or Dd → Rh⁺
dd → Rh⁻
Rhesus Factor Compatibility
Blood Transfusion
| Recipient’s Rh Type | Can Receive From |
|---|---|
| Rh⁺ | Rh⁺, Rh⁻ |
| Rh⁻ | Only Rh⁻ |
If Rh⁻ person receives Rh⁺ blood → their immune system forms anti-D antibodies → causes hemolytic reaction on second exposure.
Rhesus Factor in Pregnancy (Hemolytic Disease of the Newborn)
Occurs when:
Mother = Rh⁻
Father = Rh⁺
Baby = Rh⁺
During childbirth, some Rh⁺ fetal blood may enter mother’s circulation.
Mother’s immune system forms anti-D antibodies.
In a second pregnancy with another Rh⁺ baby, these antibodies can cross the placenta and destroy fetal RBCs → causing Hemolytic Disease of the Newborn (HDN) or Erythroblastosis fetalis.
Symptoms in baby:
Jaundice
Anemia
Enlarged liver and spleen
In severe cases, stillbirth
Prevention:
Give anti-D immunoglobulin (Rho(D) injection) to Rh⁻ mothers within 72 hours after delivery of an Rh⁺ baby.
This prevents antibody formation.