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PubMed1995

Flow cytometric analyses of the subclasses of red cell IgG antibodies.

We report on flow cytometric IgG subclass determinations of red cell antibodies using polyclonal FITC-labeled antibodies. The limit of detection of this method was 1 ng anti-D per 1 x 10(7) red cells. The inter- and intra-assay coefficients of variance were 8.2 and 2.3%, respectively. In 8 newborns with a positive direct antiglobulin test (DAT) in the gel centrifugation test (GCT), due to ABO antibodies, IgG1 was detected in all and IgG2 additionally in 4 of these cases. In 5 severe cases of hemolytic disease of the newborn (HDN) due to anti-D, large amounts of IgG1 were found, and in 3 of these 5, IgG3 in combination with IgG1. In 8 mild or moderate HDN cases (4 anti-D, 2 anti-E, 1 anti-Fya, 1 anti-Jka), phototherapy sufficed, and IgG1 was the only antibody. In 7 adult patients with malignant lymphoma and a positive DAT (GCT), only small amounts of IgG1 red cell autoantibodies could be demonstrated by flow cytometry. In 5 further patients with malignant lymphoma, a positive DAT, and severe hemolytic anemia, large amounts of IgG1 autoantibodies were found and IgG3 was also present in 3 of these cases. Flow-cytometric determination of IgG subclasses may be a useful tool in immunohematology, since subclass determinations were possible in all of these cases. This method is suited for clinical routine and offers the possibility of sufficient standardization.

Adult↗
PubMed1996

Intravenous immunoglobulin as primary therapy or adjuvant therapy to intrauterine fetal blood transfusion: a new approach in the management of severe Rh-immunization.

Maternal high dose intravenous immunoglobulin (IVIG) has shown promise in the management of severe Rh-immunization. Intravenous immunoglobulin, blocks Fe mediated antibody transport across the placenta and blocks destruction of fetal red cells and reduces maternal antibody levels. We have tried this new therapy in 6 patients with severe Rh-immunization, with high maternal antibody titres and previous hydrops and intrauterine deaths. Intravenous immunoglobulin was given from 13-18 weeks of gestation 3-4 weekly, till intrauterine transfusion (IUT) or delivery. Intensive fetal monitoring was done. No fetal hydrops or deaths occurred in any of the 6 cases. Only 2 cases needed intrauterine transfusion. IVIG delayed the onset of fetal anemia by 8-17 weeks thus deferring the need for IUT. All pregnancies continued till 32-36 weeks and all 6 babies did well in the neonatal period.

Blood Transfusion, Intrauterine↗
PubMed1986

Haemolytic disease of the newborn--the changing scene.

Between 1950 and 1970 there was a steady decline in the number of infant deaths from rhesus haemolytic disease of the newborn in the Yorkshire Region but no decrease in the number of pregnant women with antibodies. Following the introduction of Rh prophylaxis in 1970, the number of pregnant women sensitized has decreased by 70% and the number of infant deaths by 96%. The number of infants requiring exchange transfusion has also decreased by 70%. During the years 1980 to 1983 there were 163 new cases of maternal sensitization to the D antigen in the Yorkshire Region, 36 were due to failures of administration, 75 were failures of protection and 26 were in primigravidae. Eighteen of the failures of administration occurred after abortion, nine of which were surgical terminations. Antenatal prophylaxis may well have protected 64 (40%) of these 163 women. The number of pregnant women with antibodies other than anti-D now exceeds those with anti-D. The effect of these changes in incidence and clinical severity on the management of Rh D negative pregnant women is discussed.

England↗
PubMed1988

Massive feto-maternal haemorrhage: effect of passively administered anti-D in the prevention of Rh sensitization and haemolytic disease of the newborn.

Fourteen mothers carrying ABO compatible but Rh D incompatible pregnancies experienced large feto-maternal haemorrhages (estimated 188 ml, range 50-400 ml red cells). These were all treated with infusions of fresh frozen plasma containing anti-D at a mean immunoglobulin to fetal cell ratio of 129 i.u. (25.8 micrograms)/ml of fetal cells. At 48 h after the infusion 95% of fetal cells had been removed but 3 to 4 days were required for complete removal. The passively administered anti-D was detectable for up to 6-9 months but not after that time. Four of the 14 women had successful pregnancies subsequently although in two of these anti-C + D was present. Of these, one resulted in a clinically affected baby who survived exchange transfusion.

Erythroblastosis, Fetal↗
PubMed1991

Fetal liver dysfunction in Rh alloimmunization.

The liver enzymes, aspartate transaminase (AST), alanine transaminase (ALT), gamma glutamyl transpeptidase (GGT) and alkaline phosphatase (ALP), were measured in the blood of 25 fetuses with severe Rh alloimmunization at the time of their first, second and third intravascular transfusions and in 17 comparison fetuses. In the comparison group, GGT increased with advancing gestation (r = 0.7; P = 0.002), whereas ALP, AST and ALT did not correlate with gestational age. Rh hydropic fetuses (n = 8) had higher blood ALT levels than the comparison fetuses (P = 0.008) had significantly increased transaminases when compared with non hydropic fetuses (n = 17). In hydropic fetuses, AST correlated with the nucleated red cell count before transfusion (r = 0.94; P = less than 0.0001). Fetal transaminases were no longer increased in hydropic fetuses by the second (AST) or third (ALT) transfusion. In both hydropic and non hydropic fetuses, GGT increased by the second transfusion (median percentage change +85%, range -83% to +596%; P = 0.003). The rise in fetal GGT was transitory and correlated with the increase in fetal haematocrit at the first transfusion (r = 0.58; P = 0.006). This study reports liver dysfunction secondary to extramedullary erythropoiesis in Rh alloimmunization and implicates portal hypertension for the rise in fetal GGT with transfusion.

Alanine Transaminase↗
PubMed1992

Lack of relation between fetal blood gases and fetal blood flow velocity waveform indices found in rhesus isoimmunised pregnancies.

OBJECTIVE: To investigate the relation between umbilical vein blood gas components and the vascular resistance in four fetal arteries in Rh-immunised pregnancies. DESIGN: A prospective observational study over a 4-month period. SETTING: King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. SUBJECTS: Fifteen Rh-isoimmunised pregnant women. INTERVENTIONS: Pulsed Doppler examinations of the umbilical artery, fetal internal carotid artery, thoracic aorta and abdominal aorta before transabdominal fetal blood sampling from the umbilical vein on 38 occasions. MAIN OUTCOME MEASURES: Doppler flow velocity pulsatility index (PI), systolic/diastolic ratio (A/B) and resistance index (RI) in the four fetal arteries investigated were related to the umbilical vein blood gases and acid-base status (PO2, PCO2, O2-content, CO2-content, HCO3, base excess and lactate concentration). RESULTS: There were no correlations between the Doppler indices in any of the vessels studied and the blood gases components in the umbilical vein. The ratios between the corresponding Doppler indices in the different vessels were also independent of the blood gases and acid-base status and there were no significant differences in the Doppler indices in the same vessel between fetuses with blood gas values over the 75th centile and those with values below the 25th centile. CONCLUSION: This study does not support a reduction in peripheral vascular resistance in the fetal cerebrum in relation to fetal hypoxia in Rh-immunized pregnancies.

Blood Flow Velocity↗
PubMed1993

Anti-D concentrations in fetal and maternal serum and amniotic fluid in rhesus allo-immunised pregnancies.

OBJECTIVE: To investigate the relation between anti-D concentrations in maternal serum, fetal serum and amniotic fluid, and the development of fetal anaemia. DESIGN: Observational cross sectional and longitudinal study. SETTING: Regional referral centre. SUBJECTS: Sixty-one women undergoing fetal blood sampling at 19 to 36 weeks' gestation for fetal blood and haematocrit estimation for the management of Rh (D) allo-immunisation. Thirty-eight pregnancies (7 with an Rh (D) negative fetus) were tested only once but the rest had two to five fetal blood samplings. INTERVENTIONS: Ultrasound guided fetal blood sampling and amniocentesis, and automated analysis of anti-D antibody quantitation. RESULTS: There were strong correlations between maternal serum, fetal serum and amniotic fluid anti-D concentrations. Analyses of both longitudinal and cross sectional data demonstrated a decrease of the maternal/fetal serum anti-D ratio with gestation. In pregnancies with Rh (D) negative fetuses the maternal/fetal anti-D ratio was significantly lower (P < 0.0001) than in those with Rh (D) positive fetuses. The degree of fetal anaemia (delta haematocrit) was correlated with maternal serum and amniotic fluid anti-D concentrations (r = -0.55, n = 54, P < 0.0001; r = -0.57, n = 44, P < 0.0001, respectively) but there was a weaker correlation with fetal serum anti-D (r = 0.37, n = 54, P < 0.01). CONCLUSION: Anti-D concentrations in maternal serum, fetal serum and amniotic fluid are correlated with fetal anaemia. The decrease in maternal/fetal anti-D ratio with gestation suggests an increase in placental permeability for anti-D with advancing pregnancy.

Amniotic Fluid↗
PubMed1994

The effect of neuromuscular blockade on human fetal heart rate and its variation.

OBJECTIVE: To determine the effect of neuromuscular blockade on fetal heart rate and its variation. DESIGN: Case control study. SETTING: Tertiary referral fetal medicine unit in a London teaching hospital. SUBJECTS: Forty women with rhesus iso-immunisation requiring an intravascular fetal blood transfusion between 28 and 34 weeks gestation. INTERVENTION: Intravascular injection of pancuronium to the fetus prior to fetal blood transfusion in 20 cases. MAIN OUTCOME MEASURES: Comparison between the group receiving pancuronium and the control group with regard to differences in perceived fetal activity and computer derived numerical indices of fetal heart rate and fetal heart rate variation after fetal blood transfusion. RESULTS: After transfusion in the control group, there were fewer perceived fetal movements, a small reduction in fetal heart rate but no differences in number of fetal heart rate accelerations or measures of fetal heart rate variation. In the study group, pancuronium produced no change in fetal heart rate despite a virtual abolition of perceived fetal movements and fetal heart rate accelerations. Measures of fetal heart rate variation were reduced by 60%. Comparison of the pre- to post-transfusion changes between the two groups showed significant differences for all fetal heart rate indices. CONCLUSION: Fetal activity accounts for more than half the measured variation of the human fetal heart rate.

Blood Transfusion, Intrauterine↗