The vast majority of people are familiar with the common ABO blood group system, which categorizes blood into types A, B, AB, and O. However, there exists an exceptionally rare blood type known as the Bombay blood group, or hh phenotype, which stands apart from these conventional classifications. This unique blood group presents significant challenges in identification and medical management. Its rarity makes it a subject of particular interest in transfusion medicine.
The Underlying Genetics of the Bombay Phenotype
Understanding the Bombay phenotype begins with the H antigen, a foundational sugar molecule present on the surface of red blood cells. This H antigen serves as a precursor substance, acting as a base onto which the A and B antigens are subsequently built. Specific enzymes, encoded by the ABO genes, determine which additional sugar, if any, is attached to the H antigen to form either the A antigen, the B antigen, or both.
Individuals with the Bombay phenotype possess a unique genetic characteristic: they have a homozygous recessive genotype (hh) at the H locus. This genetic arrangement prevents them from producing the necessary enzyme, alpha-1,2-fucosyltransferase, which is responsible for synthesizing the H antigen. Without this foundational H antigen, even if a person inherits the genes for A or B blood types, there is no precursor molecule for the A or B transferase enzymes to act upon. Consequently, their red blood cells lack not only the A and B antigens but also the H antigen itself.
This absence of the H antigen means that, superficially, their red blood cells resemble those of a Type O individual, as neither reacts with anti-A or anti-B antibodies. The lack of the H antigen is the direct reason their red blood cells do not express A or B antigens, regardless of their ABO genotype. This genetic anomaly explains the unique and rare nature of the Bombay blood group.
Identification and Testing Challenges
Routine blood typing procedures typically involve forward grouping, where a patient’s red blood cells are tested against known anti-A and anti-B antibodies. In individuals with the Bombay phenotype, their red blood cells will not react with either anti-A or anti-B antibodies, leading to an initial misidentification as Type O blood.
Correct identification of the Bombay phenotype relies on additional testing, particularly reverse grouping and the use of specific reagents. Reverse grouping involves testing the patient’s plasma against known A and B red blood cells to detect antibodies. A person with the Bombay phenotype will exhibit strong anti-A, anti-B, and notably, strong anti-H antibodies in their plasma, which is a distinguishing feature. A true Type O individual, by contrast, possesses anti-A and anti-B antibodies but does not produce anti-H antibodies.
A specific reagent called anti-H lectin, often derived from Ulex europaeus seeds, is used to confirm the absence of the H antigen on red blood cells. Red blood cells from individuals with the Bombay phenotype will not agglutinate (clump) when exposed to anti-H lectin. This crucial step prevents misdiagnosis and ensures proper patient care.
Transfusion and Medical Implications
The presence of potent anti-H antibodies in the plasma of Bombay phenotype individuals carries profound implications for blood transfusions. These individuals can only receive blood from another person who also has the Bombay blood group. Receiving blood from any other ABO type, including what might seem like the universally compatible Type O blood, would trigger a severe and potentially fatal acute hemolytic transfusion reaction, as their anti-H antibodies would rapidly destroy the transfused red blood cells.
Finding compatible blood donors is incredibly challenging due to the extreme rarity of the Bombay blood group. Blood banks around the world maintain registries of rare blood types, but locating a match in an emergency can be difficult. Specialized planning is often necessary for surgeries or medical procedures. Patients are encouraged to donate their own blood for autologous transfusions if possible, or to rely on a small network of known Bombay blood group donors.
Considerations for pregnancy arise when a mother has the Bombay blood group. If the father has a conventional ABO blood type, the fetus may inherit genes that result in the expression of the H antigen. The mother’s strong anti-H antibodies could potentially cross the placenta and target the fetal red blood cells, leading to hemolytic disease of the newborn (HDN). This risk requires careful monitoring during pregnancy.
Global Prevalence and Origins
The Bombay blood group was first identified in 1952 in Bombay, now known as Mumbai, India, which is how it acquired its distinctive name. Globally, the Bombay phenotype is exceedingly rare, estimated to occur in approximately 1 in 250,000 individuals.
Despite its global rarity, the prevalence of the Bombay blood group is notably higher in certain regions, particularly within India and among specific communities. This increased incidence is often attributed to a higher rate of consanguineous marriages. Such unions increase the likelihood of two individuals who are both carriers of the rare recessive ‘h’ allele having offspring who inherit two copies of the allele (hh), thereby expressing the Bombay phenotype.