Background: In an ethnically diverse country like India, establishing a national rare donor registry is a massive challenge. We aimed to establish a regional rare donor registry at our center by screening the local donor population for rare phenotypes. Methods: Serological testing of O blood group donors was done using monoclonal antisera from Bio-Rad for 23 different blood group antigens, which include Rh subgroups (C,cE,e), Kell (K,k, Kpa, Kpb), P1, Duffy (Fya, Fyb), Kidd (Jka, Jkb), Lewis (Lea, Leb), Lutheran (Lua, Lub), H, M, N, S and s. We categorized the donors with rare blood phenotypes into two categories. Category-I: High-frequency antigen-negative phenotypes with a prevalence of less than 1% in our study population. Category-II: Multiple common antigen-negative phenotypes with a prevalence of less than 1% in our study population. Results: A total of 521 donors with blood group O, meeting the inclusion criteria among a total of 23567 were phenotyped for minor blood group antigens. Out of these, 85.6% (n = 446) were Rh D positive, and 14.4% (n = 75) were Rh D negative. The male-to-female ratio was 9:1. We had identified eight rare phenotypes in category-I and 18 rare phenotypes in Category-II according to the definition adopted in our study. We have noticed a significant decrease in turnaround time in providing rare blood to patients after implementing the registry. Conclusion: This is a first-of-its-kind rare donor registry established in South India. Establishing a national rare donor registry is the need of the hour in India.
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