Mechanisms of Isoimmunization. I. The Transplacental Passage of Fetal Erythrocytes in Homospecific Pregnancies

Abstract

A critical evaluation and discussion of certain technical aspects of the acid elution method and the immunofluorescent technic for the demonstration of fetal erythrocytes in maternal blood is presented. With appropriate precautions a close agreement between the two methods was obtained. Using one or both methods as applicable, base line data concerning transplacental passage were obtained in 622 unselected women, compatible with their offspring in the ABO system and not sensitized against the Rh factor. The intermittent entry of fetal erythrocytes into the maternal blood in small quantities was found to be a physiologic event. Postpartum, fetal erythrocytes were demonstrated in 50 per cent of the mothers. In approximately 10 per cent of the series, large fetal losses estimated to range from 0.5 to 40 ml. were observed. Massive transplacental hemorrhage was detected in nearly 1 per cent of the cases by examination of the maternal blood and usually but not always by overt anemia in the fetus. It was found to be the cause of stillbirth in one case. The evidence suggested that fetal bleeds usually began well before the onset of labor. Though labor itself under pathologic circumstances may be associated with transplacental hemorrhage, under ordinary conditions it was found to be of little or no significance with regard to the entry of fetal erythrocytes into the maternal circulation. Survival of fetal erythrocytes in the maternal circulation after delivery was generally found to correspond to the expected life span of red corpuscles. Apparent shortening of survival observed in several instances was probably due to the occurrence of the original spill some time before delivery. In two instances persistence of fetal erythrocytes well beyond the normal life span was observed. Both cases involved massive transplacental hemorrhage and fetal anemia with marked erythroblastemia, and mother and child were compatible to an exceptional degree with respect to blood group factors. The findings suggested the successful transplant of replicable erythroid precursor cells from fetus to mother with prolonged maternal tolerance, an interpretation supported by the results of skin homografts from offspring to mother in one case. The implications of these findings are discussed.

Comparison of two techniques for the evaluation of fetomaternal hemorrhage in RhD‐negative women: gel agglutination and haemoglobin F determination by flow cytometry

“…Fetal hemoglobin levels between ≥0.1 and >10 ml were detected by flow cytometry in all the RhD negative women tested by both methods after delivery. This was not unexpected, considering that fetal RBCs are found in the maternal circulation even in uncomplicated pregnancies (1–3), (8). Flow cytometry is able to quantify FMH and to distinguish true fetal cells, which contain HbF, from non‐fetal cells due to the physiological increase in HbF that occurs in pregnancy (or in cases of hereditary persistence of HbF).…”

“…Hemolytic disease of the newborn due to anti‐D antibodies continues to be a problem, albeit smaller in scale since the establishment and widespread acceptance of guidelines for RhD immunoglobulin administration to RhD negative women (1–7). Early studies proved the necessity for adjusting the RhD immunoglobulin dose to the volume of the fetal‐maternal hemorrhage (FMH) (8), (9).…”

Detection of Anti‐HLA Antibodies in Maternal Blood in the Second Trimester to Identify Patients at Risk of Antibody‐Mediated Maternal Anti‐Fetal Rejection and Spontaneous Preterm Delivery

“…Human leukocyte antigen sensitization can occur after a blood transfusion, organ transplantation, feto‐maternal hemorrhage, and fetal cell trafficking into the maternal circulation . It is possible, therefore, that sensitization occurred before or during the index pregnancy.…”

Quantitation of fetomaternal haemorrhage and F cells in unusual maternal blood samples by flow cytometry using anti‐D and anti‐HbF

“…In the KBT, F cells had variable staining (Figs and ) as reported before (Woodrow & Finn, ), some with sufficiently dark staining to be counted as fetal cells. Acid resistant cells were earlier found in 5 of 165 blood donors (Cohen et al , ).…”