A study recently published in Transfusion Medicine Reviews provided evidence for routine antibody testing to screen for severe hemolytic disease of the fetus and newborn (HDFN) in pregnancies with anti-Kell (anti-K) alloimmunization.
The Kell system consists of a group of proteins, or antigens, found on the surface of red blood cells. These antigens are highly capable of triggering immune responses among individuals who have not previously been exposed to them.
During a pregnancy affected by anti-K alloimmunization, the mother develops anti-K antibodies against the Kell proteins on the fetus’ red blood cells. This, in turn, can lead to HDFN.
Previous studies have sought to uncover the utility of anti-K levels, also known as titers, as a potential predictor of severe HDFN. However, these findings have been largely inconsistent and merit further study.
Read more about HDFN testing and diagnosis
The authors identified 54 prior studies of pregnancies with anti-K antibodies comprising 1761 different pregnancies. Among the 207 fetuses with severe HDFN, 204 (98.6%) had anti-K titers of at least eight.
The authors then selected six studies including 350 fetuses to evaluate the potential of an anti-K screening test, using an anti-K titer of eight as a cutoff. This test had a sensitivity of 97%, meaning 97% of patients with severe HDFN were properly categorized using this cutoff. The specificity of the test was 33.1%, meaning that 33.1% of patients who did not have severe HDFN were correctly classified as such.
These findings suggest that while this screening test can identify the majority of severe HDFN cases based on anti-K titers, there is also a relatively high false positive rate of 66.9%. This means that while some pregnancies may have elevated anti-K titers, they will not always lead to severe HDFN.
“In summary, this analysis illustrates that severe HDFN mediated by anti-K is rare among patients with an anti-K alloantibody titer <8,” the authors wrote. “Early determination of anti-K titers remains critical, and lower titers—particularly when trending upward—should prompt close monitoring.”
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