The expression of Sd(a) antigen in positive individuals is highly variable, and ranges from expression so weak that it is barely detectable, to expression so strong that the cells are agglutinated by plasma from most human donors (polyagglutination). Extremely strong expression of Sd(a) is denoted as Sd(a++). The Sd(a++) phenotype is sometimes referred to as the Cad phenotype, after a 1968 paper that identified a novel antigen in members of the Cad family from Mauritius. The Cad positive cells showed polyagglutination and reacted with Dolichos biflorus lectin, a reagent used to identify type A1 red blood cells, even though the cells were type B or O. Later research showed that strong examples of Sd(a) also exhibited polyagglutination and reaction with Dolichos biflorus, and that Cad was likely an exceptionally strong Sd(a) positive phenotype. It is believed that Sd(a) and Cad share the same antigenic determinant and are likely synthesized by the same enzyme, but there may be structural and quantitative differences in the expression of the two substances. The Cad/Sd(a++) phenotype, like the Sd(a) positive phenotype, shows autosomal dominant inheritance. Anti-Sd(a) is a naturally occurring antibody, meaning Sd(a) negative individuals produce it without having been exposed to Sd(a) positive blood through transfusion or pregnancy. Anti-Sd(a) is not typically considered to pose a hazard in blood transfusion, but as of 2018, two cases of transfusion reactions following the transfusion of Sd(a++) blood have been documented. It is suggested that people with anti-Sd(a) are transfused with "least incompatible" blood (the blood unit that gives the weakest reactions during crossmatching) to avoid potential exposure to Sd(a++) units. Anti-Sd(a) is not known to cause hemolytic disease of the newborn.
Sid blood group system
Lan blood group system
Junior blood group system
Rh blood group system
Augustine blood group system
Vel blood group
Hh blood group
P1PK blood group system