Weak D Testing:
There are many variants of the RhD antigen, some of which result in variant expression. Historically, a distinction was made between “weak D”, in which there is reduced expression of normal RhD (typically due to variants in the cytoplasmic domain of the RhD antigen) antigen, and “partial D”, in which the D antigen is altered due to variants in the exofacial aspects of the RhD antigen. While both are considered capable of sensitizing an RhD-negative transfusion recipient, only partial D patients will themselves make an anti-D when exposed to RhD-positive RBCs.
Increasingly, however, the distinction between weak and partial D has been blurred, as it is recognized that some forms of weak D are in fact also partial D.
Detecting RhD variants is important: if patients with these phenotypes are accidentally typed as RhD-negative and are then exposed to RhD-positive RBCs, they may make an anti-D antibody. Similarly, if blood from a RhD-variant donor is accidentally typed as RhD-negative and given to an RhD-negative patient, that patient may also make an anti-D antibody.
Most commercially available RhD typing sera are monoclonal and are selected specifically to not react with common RhD variants. This ensures that individuals with these variants will only type as RhD-negative and therefore only be transfused RhD-negative RBCs. Some cases of RhD variants are nonetheless discovered inadvertently amongst transfusion recipients due to weaker than expected reactions during RhD typing, or due to discrepancies with results obtained from other laboratories. Resolution of these discrepancies generally requires genotyping to determine the exact type.
When typing RBCs intended for transfusion, on the other hand, it is necessary to actively seek out RhD variants in any samples that appear to be RhD-negative, so as to avoid inadvertently sensitizing an RhD-negative transfusion recipient. Similarly, if an RhD-negative woman delivers an RhD-negative baby, RBCs from that baby should also be checked for weak or partial D expression which, if present, would necessitate the administration of RhIg. This assessment can be achieved by performing RhD typing with the use of antiglobulin reagent, which increases test sensitivity.
Whether a pregnant woman who herself types as RhD-negative should be checked for a weak or partial D (so as to avoid unnecessary exposure to RhIg) is controversial; given the safety of RhIg, many authorities to not consider this necessary.
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