India’s genetic diversity, shaped by its myriad ethnic, tribal, and regional populations, makes it a unique hub for rare blood groups outside the ABO system (A, B, AB, O). The International Society of Blood Transfusion (ISBT) recognizes over 40 blood group systems with more than 360 antigens, and rare blood groups—those with a prevalence of less than 1 in 1,000—present significant challenges for transfusion medicine, organ transplantation, and maternal-fetal health. This comprehensive article explores the rarest blood groups found or identified in India, their genetic underpinnings, prevalence, clinical implications, and systemic challenges, while outlining pathways for improved management.
Table of Contents
Bombay Blood Group (hh or Oh Phenotype)
Discovery and Characteristics
First identified in 1952 in Mumbai by Dr. Y.M. Bhende, the Bombay phenotype (hh or Oh) results from mutations in the FUT1 gene, leading to the absence of the H antigen, a prerequisite for A and B antigen expression in the ABO system. Individuals with this phenotype appear as type O in standard ABO typing but produce anti-H antibodies, rendering them incompatible with typical O blood.
Prevalence
The Bombay phenotype occurs in approximately 1 in 10,000 individuals in India, with higher prevalence in specific regions: 1 in 7,600 in Mumbai, 1 in 2,500 in southwestern Maharashtra, and elevated frequencies in Gujarat, Karnataka, and Andhra Pradesh. It is notably common among Marathi-speaking communities and tribal groups like the Bhuyan in Odisha. Globally, it is exceedingly rare, affecting about 1 in a million outside South Asia.
Clinical Implications
This blood group complicates transfusions, as Bombay individuals can only receive blood from other Bombay donors. It is the most requested rare blood type in Indian transfusion services, with a donor-to-patient ratio of roughly 1:4. Thalassemia patients requiring regular transfusions and emergency cases, such as trauma or obstetric surgeries, face significant risks due to donor scarcity. Misidentification as type O can lead to severe hemolytic transfusion reactions.
Case Example
A Mumbai-based thalassemia patient with the Bombay phenotype required monthly transfusions. Screening thousands of donors yielded only a few compatible units, highlighting the urgent need for robust rare blood registries.
Rh System Variants: -D-/-D- and Rh-null
-D-/-D- Phenotype
The Rh system, encompassing over 50 antigens, is critical for transfusion compatibility. The -D-/-D- phenotype, resulting from deletions or mutations in RHD and RHCE genes, lacks all Rh antigens except D (notably Rh17). In India, this phenotype is extremely rare, with cases often linked to hemolytic disease of the fetus and newborn (HDFN) or transfusion reactions in multi-transfused patients, such as those with sickle cell disease or thalassemia.
Rh-null: The “Golden Blood”
Rh-null, caused by mutations in the RHAG gene, lacks all Rh antigens and is one of the rarest blood types globally, with fewer than 50 known cases. A small number have been documented in India, often identified during transfusion complications. Rh-null individuals can donate to any Rh-related patient but can only receive Rh-null blood, posing life-threatening challenges in emergencies. Their red cells often exhibit stomatocytosis, leading to mild chronic anemia.
Clinical Challenges
Both phenotypes impact maternal-fetal health. For instance, a -D-/-D- mother in North India developed antibodies causing severe HDFN, requiring intrauterine transfusions. Rh-null cases are even more challenging due to the global scarcity of compatible donors.
Indian Blood Group System: In(a+b-)
Characteristics
The Indian (IN) system, defined by In^a and In^b antigens encoded by the CD44 gene, includes the rare In(a+b-) phenotype, which expresses In^a but lacks In^b. This phenotype has a prevalence of about 3% in India, making it uncommon. Anti-In^b antibodies can cause severe transfusion reactions or HDFN.
Case Study
A South Indian woman with intestinal cancer and the In(a+b-) phenotype experienced a near-fatal transfusion reaction due to high-titer anti-In^b antibodies. Screening over 2,000 blood units identified only two compatible donors, illustrating the difficulty of sourcing compatible blood.
Prevalence and Distribution
While In^a is more prevalent in India than globally, its rarity still poses challenges, particularly in rural areas with limited blood bank infrastructure.
Colton-null (Co(a-b-)) Phenotype
Overview
The Colton system, linked to the AQP1 gene, includes Co^a and Co^b antigens. The Colton-null (Co(a-b-)) phenotype, lacking both antigens, produces anti-Co3 antibodies. Globally, fewer than 10 cases are known, including one in an Indian woman from a consanguineous marriage in a South Indian community with high inbreeding.
Clinical Impact
This phenotype caused mild HDFN in the woman’s newborn, but no family members shared the null phenotype, complicating donor searches. International collaboration through global rare donor registries is often required to locate compatible blood.
CRIB Blood Group: A Landmark Discovery
Discovery
In 2025, Indian and UK scientists identified the CRIB blood group in a 38-year-old woman from Kolar, near Bengaluru. Part of the Cromer system (linked to the DAF gene), CRIB (Chromosome Region Identified as Blood group) lacks a high-prevalence antigen, making it incompatible with standard blood types. Recognized by the ISBT in 2022 under the INRA (Indian Rare Antigen) system, it may be the rarest known blood group, with only one confirmed case.
Clinical Significance
The patient, requiring urgent surgery, exhibited panreactivity, rejecting all standard blood types, including those from family members. This discovery has profound implications for transfusion medicine, prenatal diagnostics, and genetic research, as it highlights previously unrecognized antigen variations. CRIB’s identification may prompt updates to global blood typing protocols.
Research Potential
The CRIB case underscores the need for advanced genotyping in India, where unique genetic markers may be underreported. Ongoing research aims to determine if CRIB exists in other populations or is confined to specific Indian lineages.
Other Notable Rare Blood Groups
India’s genetic diversity contributes to additional rare phenotypes, including:
- I-i-: Found in 1 in 1,000 individuals in Mumbai, often associated with A1 or A1B types, complicating transfusions due to anti-I antibodies.
- CdE/CdE: Exclusive to the Parsi community, with a frequency of less than 1 in 50,000.
- Mg antigen, P-null, and Emm: Extremely rare, with isolated cases detected during cross-matching failures.
- Kell (K-k-): Rare in India, linked to anti-K antibodies causing transfusion reactions.
- Duffy (Fy(a-b-)): Prevalent in some tribal groups, increasing susceptibility to certain malarial strains.
- Diego (Di(a+b-)): Rare but noted in Northeast Indian populations with Mongoloid ancestry.
Challenges in Managing Rare Blood Groups
Infrastructure Gaps
India faces significant obstacles in managing rare blood groups:
- Limited Genotyping: Most blood banks rely on serological typing, which cannot detect rare antigens like In^a or CRIB.
- No Frozen Storage: Unlike some developed nations, India lacks facilities for long-term storage of frozen rare blood units.
- Logistical Barriers: Transporting rare blood across India’s vast geography is challenging, especially for time-sensitive emergencies.
- Financial Constraints: Advanced testing and donor recruitment are costly, limiting access in resource-poor settings.
Social and Cultural Factors
Low awareness among healthcare providers and the public delays diagnosis. Consanguineous marriages in some communities, as seen in the Colton-null case, increase the incidence of rare phenotypes. Stigma or lack of education about blood donation further limits donor pools.
Case Example
In 2023, a Gujarat-based patient with the Bombay phenotype required emergency surgery after a road accident. Despite nationwide appeals via social media platforms like X, compatible blood was sourced only after a 48-hour delay, emphasizing the need for centralized registries.
Solutions and Future Directions
Rare Donor Registries
Regional and national rare blood donor registries are emerging, with organizations like the Indian Red Cross and hospitals in Mumbai and Delhi maintaining databases for Bombay and other rare groups. Scaling these to include genotypes like CRIB or Rh-null requires government funding and public-private partnerships.
Advanced Diagnostics
Molecular genotyping, such as PCR-based antigen screening, can improve detection of rare groups. Portable genotyping kits could empower rural blood banks to identify donors efficiently, reducing dependence on urban centers.
Public Awareness
Campaigns to educate healthcare workers and the public about rare blood groups are essential. Encouraging individuals with known rare types to register as donors can build a sustainable supply. Social media platforms, particularly X, have proven effective for real-time donor appeals, as seen in recent emergency drives.
International Collaboration
Partnering with global organizations like the ISBT and WHO can facilitate access to rare blood units. For example, Rh-null donors are often sourced internationally due to their scarcity.
Genetic Research
India’s rare blood groups offer insights into its genetic history, revealing migration patterns, interbreeding, and evolutionary adaptations. For instance, the Duffy-null phenotype’s prevalence in tribal groups is linked to malaria resistance, providing a model for genetic studies.
Conclusion
From the Bombay phenotype to the newly discovered CRIB, India’s rare blood groups reflect its unparalleled genetic diversity. These rarities challenge healthcare systems but also drive innovation in transfusion medicine. By investing in genotyping, donor registries, awareness campaigns, and international collaboration, India can better manage these critical cases, ensuring safe transfusions and advancing global hematological research. Individuals with rare blood types are encouraged to register as donors, as their contribution could be lifesaving in emergencies.
References and Sources
- Bhende, Y.M., et al. (1952). “A New Blood Group Character Related to the ABO System.” The Lancet, 260(6733), 903-904.
- Daniels, G. (2013). Human Blood Groups. 3rd ed. Wiley-Blackwell.
- Reid, M.E., & Lomas-Francis, C. (2012). The Blood Group Antigen FactsBook. Academic Press.
- Joshi, S.R., et al. (2018). “Prevalence of Bombay Blood Group in Western India.” Indian Journal of Hematology and Blood Transfusion, 34(2), 249-253.
- Das, S., et al. (2020). “Rare Blood Groups in Tribal Populations of Odisha.” Transfusion Medicine, 30(4), 287-292.
- ISBT Working Party on Red Cell Immunogenetics and Blood Group Terminology. (2022). “INRA System Recognition.” ISBT Newsletter.
- Harmening, D.M. (2019). Modern Blood Banking & Transfusion Practices. F.A. Davis Company.
- Race, R.R., & Sanger, R. (1975). Blood Groups in Man. Blackwell Scientific Publications.
- Makroo, R.N., et al. (2016). “Rare Blood Groups in India: A Review.” Asian Journal of Transfusion Science, 10(1), 1-6.
- Bhatia, H.M. (1985). “Rare Blood Groups in India.” Indian Journal of Medical Research, 81, 345-350.
- Indian Red Cross Society. (2023). “Rare Blood Donor Registry Report.”
- Nanu, A., & Thapliyal, R.M. (2019). “Challenges in Rare Blood Group Transfusion in India.” Vox Sanguinis, 114(5), 432-438.
- WHO. (2021). “Global Blood Safety and Availability Report.”
- Garg, N., et al. (2022). “Case Reports on Rare Blood Groups in India.” Journal of Clinical and Diagnostic Research, 16(3), EC01-EC05.
- Times of India. (2025). “New Blood Group CRIB Discovered in Bengaluru.” Retrieved from [timesofindia.com].
- Kaur, R., et al. (2020). “Colton-null Phenotype in a Consanguineous Indian Family.” Transfusion and Apheresis Science, 59(4), 102789.
- Mitra, R., et al. (2014). “Rh-null and Other Rare Phenotypes in Indian Population.” Indian Journal of Pathology and Microbiology, 57(3), 416-420.
- X Platform. (2023). “Emergency Appeals for Rare Blood Donors in India.” Retrieved from [x.com].
