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PubMed1994

Sequence variability in the env-coding region of hepatitis C virus isolated from patients infected during a single source outbreak.

The variability of the hepatitis C virus genome was investigated in a group of German patients who developed chronic hepatitis C after parenteral administration of contaminated immunoglobulin to prevent Rh sensitization after pregnancy. The nucleotide and deduced amino acid sequence alterations of the E1 and the first hypervariable region of the E2 gene of the hepatitis C virus (HCV) genome from sera of two randomly selected patients were studied by comparison of HCV sequences obtained from the original inoculum (anti Rh immunoglobulin) and from patient sera collected in 1979 and 1989. All isolates were classified as subtype 1b but showed nucleotide insertions of up to 12 nucleotides at the cleavage site of E1/E2. Microheterogeneity of HCV genomes was found in the immunoglobulin supporting the quasispecies model of HCV distribution. Remarkable nucleotide exchanges over the 10 year period in the E1 region (0.9-5.2 x 10(-3) base substitutions per genome site per year) and especially in the first hypervariable region of the E2 gene (about 1.5 x 10(-2)) occurred. The HCV genome undergoes a selection of variants, though it is not known if this derives from mutation or selection of pre-existing rare variants.

Amino Acid Sequence↗
PubMed1983

Anti-D antibodies in D- and Du-positive women: a cause of hemolytic disease of the newborn.

Regardless of the decrease in Rh sensitization as a cause of hemolytic disease of the newborn, antenatal antibody screening must be performed in all patients to detect not only anti-D sensitization, but other less common antibodies capable of provoking hemolytic disease of the newborn. The relative incidence of hemolytic disease of the newborn due to sensitization to such irregular antibodies as Kell, Kidd, and Duffy is increasing. We report here five patients who had D- or Du-positive blood with antenatal anti-D sensitization, and whose neonates had hemolytic disease of the newborn of varying severity. Blood that is D- and Du-positive with anti-D has been classified by Tippett; such blood types lack part of the D mosaic and are considered to be "D variants" yet are typed routinely as Rh positive. Anti-D antibody produced by D- and Du-positive blood is indistinguishable from the ordinary variety of anti-D.

Black People↗
PubMed1992

Pregnancy-associated major basic protein in amniotic fluid.

The pregnancy-associated major basic protein, a protein elevated in the sera of all pregnant women, is virtually identical to the eosinophil granule major basic protein. To determine whether pregnancy-associated major basic protein is present in amniotic fluid, we examined samples from both early and late gestation by a double antibody radioimmunoassay. A total of 112 amniotic fluids were tested and all but three contained levels of pregnancy-associated major basic protein greater than 400 ng/ml. Amniotic fluid pregnancy-associated major basic protein antigenic activity was immunochemically identical to that of the eosinophil granule major basic protein and also had identical physicochemical properties such as heat stability and the need for reduction and alkylation. Although the majority of amniotic fluid samples (90 of 112) were obtained from healthy women with normal gestations, the remaining 21 amniotic fluid samples were from women with Rh sensitization and from one gestation complicated by intrauterine growth retardation.

Amniotic Fluid↗
PubMed1950

Hematologic features which may influence Rh immunization.

The biologic features which may influence Rh sensitization in the mother and hemolytic disease in the newborn are conditioned by the hereditary immunologic pattern of the subjects, the antigenic characteristic of the blood group specific substances, the character of the antibody responses, the inherent susceptibility to disease as a result of the immune mechanism, and the character and sequence of exposure to the antigenic substance. In respect to Rh-negative women, there appears to be a greater vulnerability to immunization among those of blood group A. In regard to the infant, the compatibility of the maternal-infant blood types and the part they play in the phenomenon of the competition of antigens may influence the occurrence of hemolytic disease in the newborn.

Antibodies↗
PubMed1978

Reduced dose of Rh immunoglobulin following first trimester pregnancy termination.

The efficacy and safety of a 50-microgram dose of Rh immune globulin for prevention of Rh isosensitization following first trimester vacuum abortion are evaluated in this study. A total of 1027 women undergoing abortion at three outpatient facilities participated in the study; 755 (73.5%) completed follow-up serologic screening 6 months after termination of pregnancy. None showed serologic evidence of Rh sensitization at the time of followup. No serious adverse reactions to the drug were observed.

Abortion, Induced↗
PubMed2006

Molecular characterization of GYPB and RH in donors in the American Rare Donor Program.

Transfusion of patients with sickle cell disease (SCD) has been a challenge in clinical transfusion medicine, especially when the required donor RBCs must be U- and negative for high-prevalence Rh phenotypes (hr(B), hr(S)). It is now possible to genotype donors to identify or confirm Uvar and U- phenotypes, as well as Rh hr(B)- and hrS- phenotypes, and to characterize the different RH backgrounds found in these donors. In a preliminary study of donors registered in the American Rare Donor Program, twelve different RH backgrounds were identified in eighteen hr(B)- or hr(S)- donors. These results, summarized in the current report, confirm the heterogeneous nature of these phenotypes and are relevant for selection of donor units for patients with antibodies to high-prevalence Rh antigens. Not all phenotypically similar units will be compatible, and matching the Rh genotype of the donor to the patient is important to prevent further Rh sensitization. Most donors referred were hr(B)- and carry at least one hybrid RHD-CE(3-7)-D gene that encodes a variant C antigen linked to RHCE*ceS that encodes the VS+V- phenotype. Surprisingly, the majority of donors were heterozygous, some even carrying conventional alleles, suggesting that the loss of expression of the hr(B) epitopes on RBCs is a dominant phenotype. Although antigen-matching of patients with SCD with donors for C, E, and K antigens has decreased the incidence of alloimmunization, some patients still become immunized to Rh antigens, indicating the units were not truly matched. RH genotyping can identify those patients with SCD who carry RH alleles that encode altered C, e, or D who are at risk for production of "apparent auto" and alloantibodies to Rh antigens. RH genotyping of alloimmunized patients with SCD, partnered with genotyping of donors, can identify compatible units that would also eliminate the risk of further Rh alloimmunization.

Anemia, Sickle Cell↗
PubMed1981

Rh isoimmunization: a 24 year experience at Duke University Medical Center.

A retrospective analysis was made of Rh-sensitized patients delivered of their babies at Duke University Medical Center during a 24 year period. Records of 202 obstetric patients representing 280 sensitized pregnancies from a pool of 39,910 deliveries were analyzed for past obstetric history, blood group information, antibody determinations, amniocentesis data, and details of the pregnancy and delivery. The medical records of the corresponding infants were analyzed for their neonatal course. A severity index (SI) was devised to classify the degree of severity of the erythroblastosis fetalis. A significant correlation between SI and the delta OD450 of amniotic fluid, umbilical cord hematocrit, and bilirubin was noted. The evaluation of amniotic fluid delta OD450 is considered to be the cornerstone of clinical management. Twenty-nine patients had initial Liley zone 1 determinations which decreased to delta OD450 = 0.000; however, only 10 of 29 (34.5%) of the infants were unaffected, and 13 of 29 (44.8%) had mild sensitization, four of 29 (13.8%) had moderate sensitization, and two of 29 (6.9%) had severe sensitization. The previously held concept of "critical titer" as a guide for initiating amniocentesis is challenged, and the recommendation is made that amniocentesis for amniotic fluid determination should be undertaken in any patient with a positive indirect Coombs titer.

Adolescent↗
PubMed1999

A new splenic artery Doppler velocimetric index for prediction of severe fetal anemia associated with Rh alloimmunization.

OBJECTIVE: We developed a new Doppler index for the noninvasive prediction of severe fetal anemia by means of Doppler velocimetry of the main splenic artery. STUDY DESIGN: Doppler velocimetry of the main splenic artery was performed in 85 healthy fetuses and in 22 nonhydropic study case patients (41 measurements) at risk for anemia from Rh sensitization. The deceleration angle between the line describing the average slope during the diastolic phase of the cycle and the vertical axis was measured and expressed in multiples of the median (MoM) for gestational age. Severe anemia was defined as a hemoglobin deficit (mean hemoglobin for gestational age minus measured hemoglobin) >/=5 g/dL. Anemia overall was defined as a hemoglobin deficit >/=2 g/dL. RESULTS: Mean gestational age at cordocentesis was 28.6 weeks. Severe anemia was noted on 7 occasions (12.6%) and anemia was noted on 21 (51.2%) occasions. There was a significant correlation between deceleration angle and hemoglobin deficit >/=2 g/dL (r = 0.5763, P <.0001) and also with hemoglobin deficit >/=5 g/dL (r = 0.6418, P <.0001). At deceleration angles <0. 90 MoM, a 90.5% sensitivity and a 30% false-positive rate were achieved for anemia detection. At a threshold deceleration angle of <0.60 MoM, the sensitivity for severe anemia was 100%, with an 8.8% false-positive rate. CONCLUSION: We report a new and sensitive Doppler velocimetric technique for predicting severe anemia. By means of splenic artery velocimetry, all cases of severe anemia could be identified before the development of hydrops, with a >91% reduction in the rate of cordocentesis.

Anemia↗
PubMed1976

Omental herniation. An unusual fetal complication of intrauterine transfusion.

Amniocenteses in an Rh-sensitized woman revealed the need for intrauterine transfusion to improve fetal status. Following delivery of the infant by cesarean section 7 weeks later, herniation of a segment of omentum through the anterior abdominal wall was noted. The injury was due to needle puncture during the intrauterine transfusion. The injury was repaired, and the infant recovered.

Abdominal Muscles↗
PubMed1990

Major histocompatibility complex markers and red cell antibodies to the Rh (D) antigen. Absence of association.

Between 20 and 35 percent of Rh(D) antigen-negative individuals do not develop antibodies to D even after multiple transfusions of Rh-positive red cells. To evaluate the possibility that antibody production after exposure to the D antigen was related to a major histocompatibility complex immune response gene, analysis of the HLA genotypes of 38 Rh-sensitized women and their families was performed. No significant deviations were found in the frequency of any individual HLA class I, II, or III allele or of any extended haplotype (fixed allelic combinations of HLA-B, HLA-DR, and the complement components BF, C2, C4A, and C4B). Type 1 errors due to the extreme allelic polymorphism of the HLA system, as well as the ethnic variation in patient groups, may have contributed to HLA allele-antibody responder relationships reported in earlier studies.

Female↗
PubMed1976

[Improved diagnosis fetal erythroblastosis due to Rh factors by combination of spectrophotometry (delta E 450) and a modified amniotic fluid ratio].

154 tests of amniotic fluid of 70 rh-sensitized women, won by transabdominal amniocentesis in the time between the 28th and 39th week of gestation were analysed. Besides experiential carried out spectrophotometric after Liley (estimation of delta E 450) liquor ratio were scrutinized concerning its value of statement for antenatal diagnosis in 2 variations (original liquor ratio and liquor ratio II). An equivalent pertinent judgment of delta E450 and Original liquor ratio was won. The best results were obtained with liquor ratio II and the combination of this method with delta E450. For further improvement of diagnostic reliability 2 methods of amniotic fluid analysis should be combined.

Amniocentesis↗
PubMed1976

The lecithin/sphingomyelin ratio in a high-risk obstetric population.

An experience with the lecithin/sphingomyelin (L/S) ratio in a population of high-risk obstetric patients is presented. A wide range of values in ralation to gestational age was found. A delayed rise in L/S ratio was found in Class A diabetes and Rh sensitization but was most striking in Class B through F diabetes. Chronic hypertension alone or in combination with diabetes is associated with an earlier rise in L/S ratio. A poor correlation of L/S ratio and neonatal pulmonary outcome with birthweight and gestational age was found. However, a good correlation between L/S ratio and neonatal pulmonary outcome was apparent. An L/S ratio of over 2 was universally associated with absence of serious RDS, but a low L/S ratio was less precisely predictive.

Amniotic Fluid↗
PubMed1989

Intravascular exchange and bolus transfusion in the severely isoimmunized fetus.

Eight Rh-sensitized fetuses, between 21 weeks 2 days and 35 weeks of gestation, received 31 intravascular transfusions (13 exchange and 18 bolus) and one intraperitoneal transfusion under ultrasonographic guidance. The interval between transfusions was 13.4 +/- 4.7 days. Posttransfusion hematocrit dropped at a rate of 1.0% +/- 0.6% per day. Procedure time for the bolus transfusion was shorter than for the exchange transfusion (t test, p less than 0.001). Bleeding from the puncture site complicated 10 of the 31 intravascular transfusions, without apparent maternal or fetal consequences. Fetuses were delivered between 33 and 36 weeks of gestation, after lung maturity was achieved.

Adult↗
PubMed2004

Intrauterine fetal transfusion.

The incidence of perinatal death resulting from rhesus Rh isoimmunization has dropped dramatically since the introduction of Rh immunoglobulin. However, Rh sensitization continues to be one of the leading causes of fetal anemia. Our patient is a 38-year-old woman; she gives a history of 2 uneventful pregnancies followed by 5 consecutive stillbirths. Investigations revealed an anti-D titre of 1/2048 and anti-C titre of 1/256. Ultrasound examination revealed fetal ascites at 18 weeks gestation. The fetus had a total of 9 successful intrauterine transfusions. She was delivered by an elective cesarean section at 34 weeks gestation; outcome was a healthy female baby weighing 2060 g. Examination at 9 month of age showed normal growth and neurodevelopment.

Adult↗
PubMed1978

Detection of large fetal--maternal transfusions.

Two hundred consecutive Rh-negative women at risk of Rh sensitization were screened postpartum for large fetal--maternal transfusion by two acid elution techniques. The Nierhaus modification of the Betke-Kleihauer method and the Fetaldex test were compared. In 194 of 200 women, both procedures indicated the absence of significant fetal--maternal transfusion. In 6 women a large fetal--maternal hemorrhage was detected by the Betke-Kleihauer method and in 5 of these 6 by the Fetaldex test. The overall correlation between the two techniques was 99.5%. The Fetaldex test has advantages over the Betke-Kleihauer method and is well suited for routine use postpartum and for other situations where identification or quantitation of fetal cells is desirable.

Antibody Formation↗
PubMed1989

Intra-uterine exchange transfusion under ultrasound guidance.

Thirty intra-uterine exchange transfusions (I.U.E.T.) under ultrasound guidance were performed on 15 pregnancies in 14 severely Rh-sensitized women. Our technique and a new method of catheterization of the umbilical cord are described. I.U.E.T. were commenced at 19-34 gestational weeks and repeated up to 5 times at 15 to 60 days intervals. The lowest pretransfusion fetal hemoglobin was 3 milligrams at 25 weeks. All the hydrops (4 cases) reversed a few days after the first procedure. The survival rate is 50% for hydropic fetuses and 66.6% for all cases. This technique avoids fetal hypervolemia and also too repetitive procedures by quick renewal of red cells. Catheterization offers a simple and safe access to the umbilical vein even with important fetal movements.

Blood Transfusion, Intrauterine↗
PubMed1982

Effect of plasma exchange and immunosuppression on Rho(D), viral, and bacterial antibody titers in Rh-immunized women.

Pharmacologic immunosuppression and plasmapheresis have both been advocated as adjunctive methods of treatment for Rh immunization, but a combined regimen of the two has not been attempted. We treated four nonpregnant, severely Rh-sensitized female volunteers with intensive plasma exchange and either promethazine 150 mg or prednisone 60 mg per day in an attempt to remove circulating anti-Rho(D) and prevent further synthesis of the antibody. Each patient received three or four exchanges. The Rho(D) antibody titer decreased by at least one dilution immediately following 11 of 14 plasma exchanges and was ultimately lowered at least two dilutions in all patients. In one case the titer was reduced from 1:512 to 1:16, and a low titer was maintained for the duration of treatment. However, this regimen could increase the risk of infection for a mother and/or infant, as evidenced by the concomitant lowering of viral and bacterial antibody titers in these women.

Antibodies, Bacterial↗
PubMed1991

Long-term persistence of hepatitis C virus antibodies in a single source outbreak.

The occurrence of antibodies to hepatitis C virus (HCV) was investigated in 81 patients who developed hepatitis non-A, non-B (HNANB) after parenteral administration of contaminated immunoglobulin to prevent Rh sensitization. Sera from 74 of the 81 patients (89.9%) were anti-HCV positive at either 6-12 months or 9-10 years after administration of immunoglobulin. Sera were not available from any patients at either of the times: however, 52 of 56 sera (92.9%) were anti-HCV positive 6-12 months after use of immunoglobulin, and anti-HCV was present in 45 of 65 sera (69.2%) 9-10 years after immunoglobulin treatment. Of the latter, only two of 13 (15.4%) sera from patients who recovered from hepatitis were anti-HCV positive, whereas 43 of 52 patients (82.7%) with chronic disease were anti-HCV positive. The ELISA using a recombinant antigen was found a good detector as marker for a HCV infection because 90% of patients infected by a common source became anti-HCV positive. However, 10 years after infection most patients who did not develop chronic disease no longer had detectable antibodies.

Analysis of Variance↗