Unfortunately, there is no definitive test to determine if anti-D is passive or active. Tests can be done that will suggest whether the anti-D is passive or active; however, many laboratories do not perform such testing routinely. It's both safe and efficient to consider a post-RhIG anti-D to be passive without further testing, thereby triggering a postnatal RhIG injection. Further testing would be done if serologic test results suggest an immune anti-D (e.g., 4+ reactions with D+ red cells).
Some transfusion service laboratories try to determine if anti-D is passive or immune by performing titrations to determine the titer of the anti-D. Such a protocol usually assumes that an anti-D titer greater than 4 likely represents active immunization. Unfortunately, a titer of 4 or 8 could be active or passive, although a high titer (e.g., 64 or more) almost certainly means the anti-D is immune.
Titration results can be affected by several variables:
- Red cell phenotype
- Donor antigen variability (even if the same phenotype)
- Method used
- Operator variability
Because lower titers could be due to both passive and immune anti-D, in the absence of test results that suggest immune anti-D, routine antibody titration is not a good use of time compared to assuming that anti-D is passive.
Most transfusion medicine best practice guidelines do
not recommend routine titration for patients known to be injected with RhIG and exhibiting a 2+ or less reaction with D+ red cells, i.e., test results consistent with RhIG-derived passive anti-D.