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PA21.1-6 | ABO & Rh Blood Group Systems — Part 2
ABO Inheritance and the Bombay Phenotype
Inheritance pattern:
• A and B alleles are codominant (both expressed when present together → AB phenotype)
• O allele is functionally recessive (the enzyme is non-functional, so group O is expressed only when homozygous OO or when no A/B allele is present)
• Possible genotypes: AA, AO (both express Group A phenotype), BB, BO (Group B), AB (Group AB), OO (Group O)
Bombay phenotype (Oh):
Rarely (~1 in 10,000 in India, higher in South India), the H gene itself is homozygous non-functional. No H substance is produced → no A or B antigens can be made regardless of the ABO genotype.
• Bombay individuals type as Group O on routine testing, but their plasma contains anti-A + anti-B + anti-H — the most potent combination.
• They can only receive blood from other Bombay donors.
• Clinical trap: a Bombay patient who receives routine Group O blood will have a life-threatening haemolytic transfusion reaction (because Group O cells still carry abundant H antigen).
• Bombay phenotype is more prevalent in India than in Europe — clinically relevant for the Indian physician.
CLINICAL PEARL
Universal donor and its limits: Group O Rh-negative blood is called the 'universal donor' because it lacks A, B, and D antigens. In life-threatening emergencies when blood group is unknown, O-negative packed red cells are given. However, this is NOT truly universal: (1) The plasma of O whole blood contains anti-A and anti-B which can haemolyse recipient cells if given in large volumes — use packed cells, not whole blood. (2) O-negative is only ~7% of donors, so stocks are limited and should be reserved for true emergencies. (3) Bombay patients cannot receive even O-negative blood safely.
ABO Incompatibility: Mechanism of Intravascular Haemolysis
When ABO-incompatible blood enters the circulation:
1. Pre-formed IgM anti-A or anti-B binds immediately to antigens on donor RBCs (antigen density is high — ~1 million A or B sites per RBC).
2. IgM pentamers are highly efficient at activating the classical complement pathway (two Fc regions needed to bind C1q — one IgM molecule provides both).
3. Complement cascade proceeds to completion → membrane attack complex (MAC) inserts into the RBC membrane → intravascular haemolysis (haemoglobin released directly into plasma).
4. Released haemoglobin → haemoglobinaemia → haemoglobinuria (dark urine) → acute tubular necrosis if severe.
5. Complement fragments (C3a, C5a) → mast cell degranulation → fever, hypotension, shock.
6. Tissue factor release → DIC risk in severe reactions.
This entire sequence can begin within minutes of starting a transfusion — hence the rule to observe the patient for the first 15 minutes of every transfusion.
The Rh System: D Antigen and Rh Status
The Rh system is the second most clinically important blood group system. It comprises over 50 antigens encoded by two closely linked genes on chromosome 1 (RHD and RHCE), but clinical practice focuses almost entirely on the D antigen (also called RhD).
- Rh-positive (Rh+): D antigen present on RBCs (~85% of the Indian population)
- Rh-negative (Rh−): D antigen absent (~15% — varies by ethnicity)
The D antigen is a transmembrane protein (not an oligosaccharide like ABO antigens). It is the most immunogenic of all blood group antigens apart from ABO — a single exposure to as little as 0.1 mL of Rh+ blood in an Rh-negative individual can trigger sensitisation.
Critical difference from ABO:
• There are no natural anti-D antibodies. Rh-negative individuals do NOT have anti-D in their plasma unless previously sensitised.
• Anti-D is an immune antibody — it forms only after exposure to D antigen (via transfusion or fetomaternal haemorrhage).
• Class: IgG (monomeric, crosses the placenta).
Rh Blood Group System: RhD Protein Expression