The familiar ABO and Rh systems are the most well-known methods for classifying blood, but dozens of other systems exist. Among these is the exceptionally rare H-deficient blood type, also known as the Bombay phenotype. This blood group is defined by the absence of a foundational antigen, which has significant consequences for blood transfusions. Its discovery highlights a deeper complexity in human biology.
The Science Behind the Bombay Phenotype
The H antigen is a foundational structure on the surface of red blood cells. It acts as the precursor upon which the A and B antigens are built. The FUT1 gene directs the production of the enzyme that creates the H antigen. Without a functional H antigen, the A and B antigens cannot be expressed, regardless of an individual’s ABO genetics.
An analogy is to think of the H antigen as a plain doughnut. The A and B antigens are like different flavors of frosting for type A, type B, or both for type AB. People with type O blood have the plain doughnut (the H antigen) but no frosting (no A or B antigens).
The Bombay blood group occurs when a person cannot produce the H antigen. In the doughnut analogy, they lack the doughnut itself, so no A or B “frosting” can be added to their red blood cells. This is different from type O blood, which has the H antigen but lacks the A and B antigens.
This absence is caused by a mutation that inactivates the FUT1 gene. Without the enzyme it produces, the precursor substance on red blood cells is never converted into the H antigen. Therefore, the enzymes that add A or B antigens have no foundation to build upon. The complete lack of H, A, and B antigens defines the Bombay (Oh) phenotype.
Inheritance and Rarity
The Bombay phenotype is an inherited condition. To have this blood type, a person must inherit two recessive alleles of the H gene (hh genotype), one from each parent. Parents who are carriers (Hh genotype) have one functional allele and produce enough H antigen for a normal blood type, showing no signs of carrying the trait.
The global prevalence of the Bombay blood group is low, affecting approximately 1 in 250,000 people worldwide. Its frequency varies, with the highest concentration in South Asian communities, particularly around Mumbai, India. In some communities in this region, the incidence can be as high as 1 in 10,000.
This higher frequency is attributed to consanguinity, or marriage between relatives, which is more common in certain cultural groups. When related individuals have children, the chances of both passing on a rare recessive allele like ‘h’ increase. The blood type was named after its discovery in 1952 in Bombay (now Mumbai), when a patient’s blood defied the known ABO system.
Transfusion Complications and Management
A significant challenge for individuals with the Bombay phenotype is sourcing compatible blood. Because their bodies lack the H antigen, their immune system does not recognize it. If they receive a standard blood transfusion (A, B, AB, or O), their immune system identifies the H antigen on donor red blood cells as foreign.
This recognition triggers the production of strong anti-H antibodies, leading to a severe acute hemolytic transfusion reaction. The recipient’s antibodies attack and destroy the transfused red blood cells, a process called hemolysis. This can cause kidney failure, shock, and other life-threatening complications. Therefore, people with Bombay blood can only safely receive blood from another H-deficient individual.
Managing this risk requires planning, as the rarity of Bombay blood means most blood banks do not have it in stock. National and international rare donor registries exist to connect individuals with this blood type. These registries are used to locate a compatible donor, who may be in another city or country.
Another management strategy is autologous blood donation, where individuals donate their own blood for future use. The blood is cryopreserved and stored, which is recommended for planned surgeries or pregnancy. However, this method is not an option for unexpected emergencies where there is no time to collect and store blood.
Diagnosis and Considerations in Pregnancy
Diagnosing the Bombay phenotype is complex because initial tests often misidentify it as type O. A standard forward grouping test shows no A or B antigens, leading to this preliminary classification. The discrepancy is discovered during reverse grouping or cross-matching when the patient’s serum is mixed with known type O cells. The serum of a Bombay individual contains anti-H antibodies, which react against the H antigen present on type O cells, prompting further investigation to confirm the diagnosis.
Pregnancy requires special planning for a woman with the Bombay phenotype. If the father passes a functional H allele to the fetus, the fetus will develop red blood cells with the H antigen. The mother’s immune system can be exposed to this fetal antigen, potentially causing her to produce anti-H antibodies.
These maternal anti-H antibodies could cross the placenta and attack fetal red blood cells, causing Hemolytic Disease of the Fetus and Newborn (HDFN). However, reported cases of HDFN from the Bombay phenotype are rare. This may be because the anti-H antibodies are often the IgM type, which are too large to cross the placental barrier. Despite the low incidence, the potential risk requires careful monitoring by a specialized medical team during pregnancy.