The importance of the Rh blood factor in erythroblastosis

Abstract Although 86 per cent of the population is Rh positive, isoagglutinins are not ordinarily present in the 14 per cent who are Rh negative (in contrast to the A and B antigens on which the main blood groups are based); in an individual who is Rh- (who does not naturally have the Rh antigen), agglutinins can be produced by the introduction of the Rh antigen into the blood stream. This introduction can be accomplished either by transfusion or by transfer, during pregnancy, of the Rh antigen from the fetal to the maternal circulation. When the mother is Rh- and the father is Rh+, either 50 or 100 per cent of the offspring will be Rh positive, the difference in percentage being dependent on whether the Rh factor in father is homo- or heterozygous. If fetal blood containing the Rh factor crosses the placental barrier and gains access to the maternal circulation, agglutinins may be produced in her blood. If agglutinins are produced either as a result of direct intentional transfusion or by occult transfusion from the fetus, the subsequent introduction of large amounts of blood containing the Rh antigen will result in the agglutination of this newly introduced blood and a fatal transfusion reaction may occur. When it becomes necessary to transfuse an infant suffering from erythroblastosis, the mother's blood should never be used. If, as we believe, the disease is due to the effect on the fetus of agglutinins transmitted to it from the maternal circulation, further introduction of maternal blood would result in the introduction of more agglutinins which would aggravate the disease. It has been contended that Rh negative blood should always be used to transfuse these infants because, in spite of the fact that they are practically always Rh positive, there is a possibility of free anti Rh agglutinins being present in their blood stream. We have not observed such agglutinins and have been unable to find a record of their demonstration. It may be questioned, therefore, whether it is necessary to transfuse with Rh negative blood on this basis. If cells and serum of patient and potential donor show no agglutination after incubation at 37°C. for one hour followed by centrifugation at 600 revolutions for one minute, the blood of this donor can be used with safety, regardless of whether it is Rh positive or Rh negative. Since the majority of women who give birth to babies with erythroblastosis are known to be Rh negative and may show anti-Rh agglutinins, it is essential to use blood from a known Rh negative donor if it becomes necessary to transfuse one of these women. Since the Rh factor is present in approximately 86 per cent of the general population, about 12 per cent of all marriages will be between couples where the wife is Rh negative, and the husband Rh positive. It is in this group that the wife is capable of becoming sensitized to the Rh factor and of subsequently reacting on the fetus to produce erythroblastosis. Erythroblastosis, however, occurs in only a small percentage of these women and in our experience has been found in only about 0.1 per cent of all pregnancies (The Chicago Lying-in Hospital). To account for the difference between potential and actual incidence, there are several conditions which may contribute: (1) in childless or one-child marriages the limitation in the number of offspring makes the production of erythroblastosis impossible, (2) the Rh antigen in the infant may vary in its ability to stimulate the production of agglutinins in the maternal blood, (3) the ability of the placenta to prevent the passage of the Rh antigen may vary, (4) the maternal response to the introduction of the Rh antigen into the blood stream may vary, (5) the ability of the placenta to permit passage of agglutinins may vary. It becomes apparent that although a fundamental incompatibility between the genetic constitution of the male and female germ cells may create a situation in which the occurrence of erythroblastosis becomes a possibility, there must be other superimposed factors which determine whether or not the possibility will be realized. A few women giving birth to babies who appear to suffer from erythroblastosis are Rh positive and a few infants suffering from the disease are Rh negative. It may be possible that these infants are actually suffering from a different disease entity. It is certain that severe jaundice or generalized edema can occur independently of erythroblastosis, and it is possible that in a small proportion of those infants who have the fundamental disturbance in the formation and destruction of erythrocytes which is usually characteristic of erythroblastosis, the condition may be a response to an ontirely different etiologic agent. Only further investigations can settle this point. It seems justifiable, however, to conclude that in any case where the diagnosis of erythroblastosis is doubtful, support for the diagnosis is obtained by finding the maternal blood Rh negative and the paternal and infant blood Rh positive. If the mother is Rh positive, the diagnosis of erythroblastosis is less probable.