A synthesis of different expert opinions regarding the diagnostic challenges involved in Kell (K) antigen alloimmunization leading to hemolytic disease of the fetus and newborn (HDFN) has been recently published in Lancet Hematology.
The value of antibody titration as a screening test for K alloimmunization in pregnancies is a controversial subject. The authors gathered information from different studies, guidelines and expert opinions and summarized them in a viewpoint study.
“Titration is a semiquantitative method for assessment of alloantibody concentrations that involves doubling dilutions of serum-containing antibodies until the antibody is no longer detected when incubated with antigen-positive cells,” the authors wrote.
Is there an optimal anti-K cutoff value?
An anti-K 1:4 titration appears to be the optimal cutoff value for determining a moderate risk of K HDFN occurrence that requires further monitoring. However, there are reports of K-HDFN in pregnancies with an anti-K 1:2 titration.
According to most guidelines, anti-K titration should always be performed with the same lab and the same methods in each individual pregnancy, in order to ensure appropriate comparability. In pregnancies with an anti-K titration above 1:4, titration monitoring should be done monthly until the 28th week of gestation, and then every two weeks until birth.
The importance of anti-K monitoring
In most settings, anti-K titration determines the need for median cerebral artery (MCA) doppler ultrasound. MCA doppler is the method of choice for detecting fetal anemia and recognizing the need for intrauterine blood transfusions. An anti-K titration value over 1: 32 by itself means that there is a high possibility a fetus requires an intrauterine transfusion.
Despite their diagnostic utility, most of the experts included in the study do not recommend anti-K monitoring after performing intrauterine transfusion because it does not predict the success of the procedure.
Currently, intrauterine transfusions represent the only available treatment for pregnancies complicated with K alloimmunization. Neonatal Fc receptors (FcRn), currently investigated in clinical trials, could prevent the placental transfer of anti-K antibodies, reducing the need for intrauterine transfusion.
