Is the Antiglobulin Test a Good Marker for Predicting the Development of Hemolytic Disease of the Newborn in ABO Incompatibility?

We read with great interest the article by Valsami et al1Valsami S. Politou M. Boutsikou Τ Briana D. Papatesta M. Malamitsi-Puchner A. Importance of direct antiglobulin test (DAT) in cord blood: causes of DAT (+) in a cohort study.Pediatr Neonatol. 2015; 56: 256-260Abstract Full Text Full Text PDF Scopus (16) Google Scholar that reported the importance of the direct antiglobulin test (DAT) in cord blood for predicting the development of hemolytic disease of the newborn (HDN). They concluded that, although ABO incompatibility remains the main cause of a positive DAT, other causes, such as alloimmunization and drug interactions should also be investigated. In addition, they suggested that the relevant impact of DAT positivity on the development of HDN should be considered. Although we agree with their conclusion, we think that the study has many limitations and therefore, we would like to make some constructive comments on their article. Firstly, although they mentioned that a positive DAT in ABO incompatibility is considered a major risk factor for the development of severe HDN, they did not present data for a control group who had negative DATs. By contrast, the positive predictive value of a positive DAT for the development of HDN is as low as 23%.2Dinesh D. Review of positive direct antiglobulin tests found on cord blood sampling.J Paediatr Child Health. 2005; 41: 504-507Crossref PubMed Scopus (51) Google Scholar This is due to several factors: (1) the expression of A and B blood group antigens on fetal red blood cells (RBCs) is low; (2) ABO antibodies are mainly of the immunoglobulin G2 subtype, which cannot destroy RBCs intensely; and (3) ABO antigens are present on many tissues other than RBCs, resulting in a low binding level of these antibodies to RBCs and therefore, less severe hemolysis.3Izetbegovic S. Occurrence of ABO and RhD incompatibility with Rh negative mothers.Mater Sociomed. 2013; 25: 255-258Crossref Google Scholar Secondly, it is interesting to note that no case of positive DAT was attributed to rhesus (Rh) alloimmunization in their study. However, the severity of HDN in Rh alloimmunization is generally well correlated with DAT positivity; hence, some cases could be expected whose positive DATs are related to Rh alloimmunization because the concomitant presence of ABO isoimmunization and Rh alloimmunization has a milder HDN severity than Rh alloimmunization alone. They reported four cases of A/O group incompatibility with positive DATs who were also Rh-positive infants born to Rh-negative mothers. DAT positivity in these cases was attributed to ABO incompatibility. However, this was possibly due to the destruction of some erythrocytes by natural ABO isoagglutinin; therefore, a less aggressive Rh alloimmunization reaction ensued. Finally, there is no information related to antenatal screening of these cases for fetal anemia and, hence, if any of the patients needed transfusion. In addition, there is no information related to evaluation of the morphologic features of erythrocytes. In summary, all newborn infants, particularly those with blood group incompatibility, should be monitored for jaundice early in life. DAT alone is an unreliable marker to predict the development of HDN, particularly in newborns with ABO incompatibility. Therefore, the combined use of the DAT with clinical findings, red blood cell indices, and a blood smear would be more beneficial than the use of the DAT alone for predicting the development and severity of HDN, particularly in cases of ABO incompatibility. The authors declare that they have no financial or nonfinancial conflicts of interest related to the subject matter or materials discussed in the manuscript.