Prevention of Rh-Haemolytic Disease: A Third Report

Abstract

In previous papers we described experiments in which Rh immunization of Rh-negative male volunteers was successfully prevented by the intravenous injection of plasma containing a high titre of incomplete anti-D. In the present paper we describe experiments which show that Rh-positive foetal cells can be cleared from the circulation of Rh-negative women as effectively as the Rh-positive adult cells were cleared from the Rh-negative men. On three occasions we gave 10 Rh-negative post-menopausal nulliparae 5 ml. of Rh-positive foetal blood intravenously. In five of them each infusion was followed by an intramuscular injection of 5 ml. of anti-D gamma2-globulin, and in each case this resulted in the foetal cells being rapidly cleared from the woman's circulation. The other five women did not receive the anti-D gamma-globulin and served as controls. One of these controls and none of the treated women developed immune anti-D, a result which, though it does not demonstrate that protection was achieved, does rule out the possibility of this technique enhancing antibody production. To find out if there is any relation between transplacental haemorrhage and labour, blood samples were taken from 200 women during the week preceding and the 48 hours following labour. Tests for foetal cells showed that in 135 patients none was present either before or after labour. Of the 65 where transplacental haemorrhage had occurred, in six this had taken place before labour and had disappeared after it. In 19 patients cells were present both before and after delivery, and in 40—that is, two-thirds—cells were not there before delivery but were present afterwards. We therefore consider that the majority of cases of transplacental haemorrhage occurred during labour or very shortly before it. Forty-seven haemorrhages were estimated to be less than 0.25 ml. of foetal blood in the maternal circulation, and of the 18 larger foetal haemorrhages 14 (78%) had occurred during or just before labour. To find out if there is any relation between the presence of foetal cells in the maternal circulation after delivery and subsequent Rh immunization, a new series of Rh-negative primiparae is being examined for foetal cells in the maternal circulation after delivery, and if the baby is Rh-positive the serum of the women is being tested for antibodies three and six months later. Out of 216 women tested, no foetal cells were found in 135, and three of these developed anti-D; of 81 women in whom foetal cells were found, 10 developed anti-D. There is thus a statistically significant relation between the detection of foetal cells and subsequent antibody production (P = 0.005); moreover, the greater the number of foetal cells found the greater is the likelihood of immunization. A possible reason why Cohen and Zuelzer (1964) failed to find this relation is discussed. Some details of the design and organization of a clinical trial of anti-D in selected women are given. For the trial the number of foetal cells after delivery is being used to detect Rh-negative primiparae “at risk” of Rh immunization, and alternate cases of such women are being given 5 ml. of intramuscular gamma2-globulin with a high anti-D titre immediately after the birth of the baby. At the time of writing, this clinical trial has been in progress for only five months, but already the three-month follow-up shows that none of the six protected cases has any evidence of immune-antibody formation, while three out of eight untreated controls have produced immune anti-D. This preliminary result not only encourages the hope that a considerable proportion of Rh immunization can be prevented, but, in addition, it provides confirmatory evidence that women with a high risk of Rh immunization can be detected after delivery by examination of their blood for foetal cells. In a note on the Kleihauer technique for the detection of foetal cells attention is drawn to the fact that certain women cannot be scored for the presence or absence of these because their blood contains not only large numbers of cells which look like foetal ones but also large numbers which are intermediate between adult and foetal cells in appearance. It seems probable that these cells with uneluted or partially eluted haemoglobin are of maternal origin. © 1965, British Medical Journal Publishing Group. All rights reserved.