The tale of rare human blood groups

Mercy Rophina

“Although our scientific understanding of the functions of blood is more sophisticated than ever, we remain in thrall to its primal mystique”

The historical timeline of the mystical lifeline fluid

Little did the ancient people know about the biology or functions of human blood, but they always believed the “two-faced nature of blood” - a symbol of both life and death. Blood has always been regarded as “regenerative fluid” in human history and people believed that transfer of new blood to a sick person would restore his or her health. Around 1620s, when study of blood began acquiring deeper scientific grounds, English physician William Harvey provided the revolutionary insight that human blood is circulated from the left side of the heart through arteries and returned to the right side through veins.

Initial records of blood transfusions in history

History recorded its first direct blood transfusion in the year 1667, when physician Jean-Baptiste Denis transfused 12 ounces of blood from a lamb to a feverish young man. Reports say that the young man recovered quickly and the transfusion was successful. Shortly afterward, Denis performed three more transfusions where the last two didn't go as expected. The patients died and soon the Royal Society passed bans on blood transfusion procedures. There came a temporary blockade in exploring the clinical usage of human blood. A few years later, a British obstetrician recorded the first successful human-to-human blood transfusion in 1818 by introducing the earliest blood transfusion apparatus.

Discovery of variability

The idea of using blood for treating illness became viable in 1900, when Karl Landsteiner discovered the “human blood types''. He discovered and reported that sera from certain donors caused RBCs to clump together. This discovery brought a major fact to the limelight that human blood varies from person-person. Landsteiner and his colleagues identified and reported the presence of two major antigens expressed on the surface of human RBCs that decides the compatibility of blood between two individuals - A and B antigen/agglutinogens. Not just stopping with this, there was a in the mid 19’s, when blood transfusion procedures incorporating ABO compatibility checks were well established and practised for nearly three decades. A mother of a still born child who was transfused with ABO compatible blood from her husband was reported to experience severe adverse reactions. This incident marked the discovery of yet another major antigen - RH factor

Beyond the ABO and RH horizon

There are more than 40 different blood group systems related to different types of RBC antigens. Kell, Duffy, Kidd, Lutheran - Do they even sound familiar to us ? These “not so well known” blood groups usually come to focus of attention only after encountering a clinically significant adverse reaction in a transfusion or pregnancy setting. Here is a quick interesting story about one of the rare blood groups identified in India.

The Bombay blood group story

This rare phenotype was first discovered in Bombay by Dr. Y.M. Bhende in 1952, when a railway worker and a stab wound victim needed blood transfusion. Over 160 donors were screened of which only one donor, who was also a resident of Bombay was found to match. This was later termed as “Bombay blood type”.


The molecular mechanism behind this is the “H antigen”. This antigen was identified as the precursor of ABO antigens and its absence marked the complete absence of expression of A and B antigens. Here we have a quick and simple illustration

Are rare blood groups really rare?

In transfusion practices, blood is termed “rare” when the RBCs lack a high frequency blood group antigen or that lacks multiple common antigens as they will act as potential donors for those patients who developed multiple antibodies. A rare blood group can be found at a frequency of 1 in 1000 in any given population. India is an abode of one of the rarest blood groups in the world - “Bombay (Oh) phenotype”, which has been reported from the length and breadth of the nation. In addition to this, there are reports of other rare blood antigens including In(a+b-), Co(a-b-), I-i-, CdE/CdE (ryry) and Mg from India. Highly unproportionate ratios of donors and patients with rare blood make it difficult to meet the demand and supply.

Indigenous blood group profiling and maintenance of rare donor repositories

There exist multiple ways of testing human blood groups. Serological blood group typing remains the gold standard method of investigation till date. With the advent of various high throughput sequencing techniques, extended blood profiling on population scale has become a reality. Countries including Australia, Netherlands have utilized large population scale sequencing data to decipher the landscape of rare blood groups in the nation. Numerous efforts to create awareness about rare blood groups and to maintain regional repositories are budding in India. The initiative to build a rare donor registry in Kasturba Hospital blood bank, Karnataka is one of the best examples.

Where do we stand and where are we heading?

Blood transfusions are today one of the commonest medical interventions and it is estimated that annually over 10 million units of blood are transfused in India. Apart from the ABO blood group systems there are a number of blood group systems now encompassing a number of blood group antigens now known. While serology and genotyping can today identify a number of additional common antigens, it is impossible with the current state of the art technologies to identify all antigens.

GUaRDIAN Rare Blood Group Genomics Initiative

The rare blood groups become important especially for people requiring chronic transfusions. Unfortunately little has been studied in the country on the prevalence of rare blood groups except a few handful of antigens, like the Bombay blood group. Additionally, despite being a large and diverse country, We do not still have a Rare Blood group Registry and a systematic mechanism to make available blood units when in need.


CSIR Institute of Genomics and Integrative Biology have been one of the pioneers in genomics research and implementation in the area of rare diseases in the country through the Genomics for Understanding Rare Diseases India Alliance Network (GUaRDIAN). GUaRDIAN today is a nationwide network of over 280 clinical collaborators from over 70 centres across the country, making it one of the largest networks in the area of rare disease research in the country.


The GUaRDIAN Rare Blood Group initiative aims to create a collaborative network of clinicians involved in transfusion Medicine to understand the genetic makeup of rare blood groups in India and also develop the knowledge base, resources and tools to enable genomic applications in Rare Blood groups in the country.


We invite clinicians involved in Transfusion Medicine who would be interested to be part of the initiative from across the country.



Contact
Dr Vinod Scaria vinods@igib.in

Useful Links

GUaRDIAN http://guardian.meragenome.com
IndiGen http://indigen.igib.in
CSIR IGIB http://www.igib.res.in