Prevalence, serologic and genetic studies of high expressers of the blood group A antigen on platelets*

Abstract

Objective/Aim: The aim of this study is to describe the distribution of the platelet blood group A antigenicity in Euro-Brazilians (EUBs) and Afro-Brazilians (AFBs).Background: A small but significant proportion of individuals express high levels of A or B antigen on their platelets corresponding to the erythrocyte ABO group. The mechanism of increased antigen expression has not been elucidated.Material/Methods: A cohort of 241 blood group A donors was analysed by flow cytometry. Although mean fluorescence intensity (MFI) is a typical continuous variable, platelets were screened and divided into two categories: low expressers (LEs) and high expressers (HEs). A three-generation family was investigated looking for an inheritance mechanism.Results: The prevalence of the HE platelet phenotype among group A1 donors was 2%. The mean of MFI on platelets of A1 subgroup of EUBs differs from that of AFBs (P = 0·0115), whereas the frequency of the HE phenotype was similar between them (P = 0·5251). A significant difference was found between sexes (P = 0·0039). Whereas the serum glycosyltransferase from HE family members converted significantly more H antigen on group O erythrocytes into A antigens compared with that in LE serum, their ABO, FUT1 and FUT2 genes were consensus. The theoretically favourable, transcriptionally four-repeat ABO enhancer was not observed.Conclusion: The occurrence of HE in several members suggests familial aggregation. Indeed, in repeated measures, stability of the MFI values is suggesting an inherited condition. Factors outside the ABO locus might be responsible for the HE phenotype. Whether the real mechanism of inheritance is either of a polygenic or of a discrete Mendelian nature remains to be elucidated.

The Blood Group A Genotype Determines the Level of Expression of the Blood Group A on Platelets But Not the Anti-B Isotiter

“…This procedure allowed us to exclude a prozone phenomenon, or an underestimation of the antigen expression. In accordance with previously published studies [6,7,8,9], we showed that the presence of an A 1 allele had the greatest impact on A-antigen density. An about tenfold increased difference of A antigen expression was discernible between platelets from A 1 and A 2 donors.…”

“…While it has been established that group A 2 platelets carry considerably less A antigen than those of an A 1 phenotype [3,6,7,9], their differentiation from group O platelets by flow-cytometric analyses were inconclusive. Cooling et al [6] suggested that A 2 platelets possess a Bombay-like phenotype, lacking both A and H antigen.…”

“…Mutations in the FUT1 or FUT2 gene, resulting in larger quantities of H antigen available for conversion to A antigen have also been debated, but no effective polymorphisms were detected [9]. An autosomal dominant trait was discussed, but mechanisms of inheritance have yet to be defined, as are its molecular origins [7,8,9]. …”

“…Thus, A 1 donors can be classified into low or high expressers [8]. The frequency of the high-expresser phenomenon in an A 1 population is about 2-7% [8,9]. …”

Platelet Transfusion - the Art and Science of Compromise

“…The recipients apparent refractoriness was only associated with the transfusions from the donors with the high expression phenotype; therefore, the authors concluded that donor PLTs with high levels of B antigen, in combination with recipient's ‘high titer' anti-B, were associated with lower than expected post-transfusion PLT increments. Subsequent studies have demonstrated that there are different patterns of A and B antigen high expression on PLTs (that PLTs from group A 2 donors tend to express group O levels of A antigen) and that the frequency of PLT A and B high expression is fairly constant between different populations (2-7%) [33,34,35,36,37,38]. …”