[Weak D (Du) phenotype and pregnancy].
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Antibodies, Monoclonal↗
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On a much higher than reported incidence of anti-c in R1R1 patients with anti-E.
A previous study involving tube IATs, untreated RBCs, and a low ionic-strength additive reagent revealed that approximately one-third of R(1)R(1) patients with anti-E have a concomitant anti-c. However, the current study finds a much higher incidence of anti-c in such patients, using gel technology in conjunction with ficin-pretreated RBCs. Results of antibody identification studies and transfusion records of 82 R(1)R(1) patients with anti-E were reviewed. Serologic test methods included a LISS wash solution for tube IATs (15 min at 37 degrees C, anti-IgG), ficin-tube IATs (30 min at 37 degrees C, anti-IgG + anti-C3), and gel IATs (untreated or ficin-treated RBCs or both, anti-IgG gels). LISS-tube or gel IATs with untreated RBCs revealed anti-c in 32 patients with anti-E. When gel-IAT and ficin-pretreated RBCs were used, 21 additional patients with anti-E were found to have anti-c. In samples from 26 R(1)R(1) patients with anti-E, anti-c was not demonstrable by ficin-gel IATs, and in 3 cases, the ficin-gel tests were inconclusive. In five cases in which E- RBCs not tested for c antigen were transfused to patients found by ficin-gel IAT to be without anti-c, all subsequently performed crossmatches with E-, c-untested RBCs were compatible. The incidence of anti-c in R(1)R(1) patients with anti-E in this study was 32 of 82 (39%) with untreated RBCs and 53 of 82 (65%) when the ficin gel data were included. The latter is significantly higher than the 32 percent incidence previously reported (p = 0.0001). Accordingly, all patients at our facility with an Rh antibody are now tested for those additional Rh antibodies they can make, as predicted from their Rh phenotype. The data from this study strongly support the selection of R(1)R(1) RBCs for all c- patients with anti-E.
Autoantibodies↗
The pregnant Rhesus negative Nigerian woman.
OBJECTIVE: Alloimmunisation to Rhesus D (RhD) is a major factor in perinatal morbidity and may result in the compromise of the woman's obstetric career. In Nigeria accurate population based studies to determine the prevalence of Rhesus negative women and the incidence of alloimmunisation are lacking, hence we undertook to study pregnancy outcome in Rhesus negative women. METHOD: We studied retrospectively sixty-seven RhD negative women over a two year period; information was obtained from the case-file of all pregnant women who presented to the ante-natal clinic and were identified as Rhesus negative. This was corroborated with the blood bank record over the same period. RESULT: Forty per cent of these were nulliparae with an average of 0.5 abortions. Only 20% had the blood groups of their husbands documented, and only four babies born to these women had their Rhesus group recorded. Six of the babies appeared to have been severely affected by Rhesus isoimmunisation. Three of these had an exchange blood transfusion (EBT); all who had an EBT had a satisfactory outcome. Out of the other three, there were two neonatal deaths and one fresh stillbirth. Fourteen babies had neonatal jaundice with a mean bilirubin level of 6 mg/dl, all of which were mainly unconjugated. Evidence for the administration of anti D was obtained in only three patients; all had one ampoule (dose in i.u and/or _g not stated) administered within 72 hr. CONCLUSION: This preliminary study has shown that isoimmunisation due to Rhesus incompatibility is poorly studied among Nigerian women with many questions unanswered; therefore there is an urgent need for a management protocol for this condition, which will include both the clinicians and the laboratory physicians.
Erythroblastosis, Fetal↗
[Prevention of fetomaternal anti-rhesus-D allo-immunization: methods used and topics discussed].
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Adult↗
[Epidemiology of anti-D allo-immunization during pregnancy].
The number of women exposed to a risk of anti-D allo-immunization who require care depends on the number of pregnancies, the distribution of blood groups in the Rhesus D system, and the number of allo-immunization risk situations as well as the chosen prevention protocol. In 2004, there were 790,000 pregnancies in metropolitan France. The total number of conceptions (adding abortions, voluntary interruptions, ectopic pregnancies and in utero fetal deaths) would be to the order of 1,100,000 to 1,200,000. Since 15% of the French population is RhD-negative, 15% of pregnant women or women who have delivered are RhD-negative, which would correspond to 160,000 to 180,000 women exposed to a risk of anti-D allo-immunization. Two strategies could be evaluated: prevention targeting risk factors and systematic prevention from 28 weeks gestation. Both strategies involve treatment with anti-D anti-globulins to RhD-negative women with an RhD-positive newborn. Targeted prevention would involve 160,000 to 190,000 doses for 130,000 to 150,000 women. The systematic approach would consist in 300,000 to 340,000 doses for 250,000 to 280,000 women. This number could be lowered by reserving treatment for women with a RhD-positive partner (210,000 to 230,000 doses for 260,000 to 290,000 women), but this would require a precise contract between the physician and the woman. Another way to reduce the number of doses would be to determine the Rh group of the fetus either by ovular samples or by genotyping on maternal blood. This would give about 200,000 to 220,000 doses for 240,000 to 270,000 women. In light of the literature, the systematic protocol would probably reduce the number of immunized women, the current estimation being 700 women still immunized in France and the goal being a reduction to a residual 200. The number of infants at risk of in utero maternal allo-immunization (fetal death, anasark, anemia) or after birth (jaundice, severe anemia) is not known in France and could be the cause of a few deaths with involvement of about a hundred children. In light of experience in other countries, the systematic protocol would enable avoiding a certain number of these deaths.
Female↗
[Comparison of the efficacy of different methods for the prevention of anti-D allo-immunization during pregnancy: targeted strategy limited to risk situations or associated with systematic prevention in the 3rd trimester].
BACKGROUND: In France, anti-Rh prophylaxis is currently based on systematic postnatal prevention which has validated efficacy (relative risk=0.04 versus placebo), associated with targeted antenatal prevention in the event of situations raising a risk of fetomaternal hemorrhage. In most industrialized countries, a systematic prevention policy is applied with immunoglobulin injections for the above cited situations and during the third trimester to cover the risk of spontaneous occult fetomaternal hemorrhage occurring at the end of pregnancy. OBJECTIVE: Compare the efficacy of two strategies for antenatal prevention. MATERIAL AND METHODS: Review of the literature of published comparative studies. Eleven studies were retained (two randomized trials, seven comparative studies, one before-after study, one population-based study) including more than 30,000 treated patients. RESULTS: Globally, immunization rate was to the order of 1.5% (1.2-1.9%) for targeted prevention limited to situations at risk and to the order of 0.2% (0-0.9%), all parities included, for systematic antenatal prevention. Comparative analyses have reported significant odds ratios of 0.20 and 0.37 in all subgroups. CONCLUSION: Despite the heterogeneous nature of the published studies, available data are in favor of systematic prevention: either with a 300g dose at 28GW or 100g at 28GW and 34GW complementary to the postnatal prevention. Few data are available on the real perinatal benefit of systematic prevention.
Female↗
[Adverse effects and patient information].
Anti-D prophylaxis should be proposed to all RhD negative non-sensitized pregnant women, after delivering an information concerning both Rhesus disease and anti-D immunoglobulins. This information must be delivered as a written document and the patient's oral consent is required before administration of the anti-D immunoglobulins. Anti-D immunoglobulins currently used in France for prophylaxis are extracted from plasma of hyperimmunized paid donors. Even if all the conditions of viral safety are fulfilled in the preparation of anti-D immunoglobulins, they remain blood derived products. As such, prescription of anti-D immunoglobulins should follow legal rules concerning tracability and information. Refusal of rhesus prophylaxis can occur but should be transcribed and motivated in the patient's chart. Administration of anti-D immunoglobulins is usually well tolerated. Reactions to hemolysis of fetal Rhesus positive red cells can occur but remain rare and linked to important foeto-maternal hemorrhage. They can be easily prevented or treated by anti-inflammatory drugs. Patients can be vaccinated against rubella in the post-partum period even though they will receive a concomitant prophylaxis with Rh immunoglobulin. Persistence of passive anti-D in maternal circulation after injection lasts several weeks or months and could have various consequences. In the mother: it can interfere with diagnosis of active anti-D immunization. In most cases, it may be possible to differentiate passive and immune anti-D. When reliable information concerning date and dosage of antenatal anti-D prophylaxis are available. In the newborn: anti-D immunoglobulins can pass through the placenta and enter the fetal circulation, coat the D positive fetal red cells and give positive DAT. Positive DAT is reported in 5 to 15% of the newborns following rhesus prophylaxis in the third trimester but with no report of anemia or jaundice. In absence of ABO incompatibility, no additional investigation is needed in these newborns.
Erythroblastosis, Fetal↗
[Prevention of fetomaternal rhesus-D allo-immunization. Perspectives].
At present, rhesus prophylaxis concerns RhD negative pregnant women, even though 30 to 40% of them are bearing a RhD negative child. Knowing the RhD fetal genotype could change this quite irrational practice of prophylaxis (exposing many more women than needed to blood derived products) without reducing its efficacy. RhD fetal genotype determined on amniotic fluid has an excellent sensitivity. Presence of silent D genes slightly impairs its specificity which remains acceptable. However women have to be informed of possible false positives. Fetal RhD genotyping on maternal blood is more complex. Sensitivity is good from 10 GW and excellent after 15 GW. In case of a first negative result, it is recommended to control fetal RhD on a second sample drawn a few weeks later. Another new perspective for rhesus prophylaxis is the attempt to substitute polyclonal IgG anti-D into human monoclonal IgG anti-D. The main difficulty is to elaborate monoclonal antibodies with a capacity to neutralize RhD positive red blood cells equivalent to those of polyclonal anti-D. A new generation of antibodies is in process and preliminary clinical results are suggesting a possible use of these monoclonal antibodies for future rhesus prophylaxis but long-term follow-up is required to draw further conclusions.
Erythroblastosis, Fetal↗
[Prevention of fetomaternal rhesus-D allo-immunization. Practical aspects].
RhD prophylaxis concerns RhD negative women, who are non-sensitized against D antigen during and at the end of their pregnancy with a RhD positive child. RhD prophylaxis includes targeted prophylaxis (prevention of anti-D immunization after feto-maternal hemorrhage (FMH) induced by prenatal events and delivery) and routine antenatal D prophylaxis (prevention of anti-D immunization resulting from spontaneous FMH in the last trimester of pregnancy). Targeted prophylaxis should be applied regardless of the gestational age and a dose of 100microg anti-D is usually enough (200microg is the lowest dosage currently available in France). However it is recommended to quantify the volume of feto-maternal hemorrhage to avoid administration of a dose of IgG anti-D less than 20microg per ml of fetal red blood cells. Efficacy of prophylaxis relies also on the delay between the sensitizing event and the injection of anti-D, delay should be less than 72 hours. Intravenous administration of anti-D allows immediate neutralization of D positive fetal red blood cells and should be, if possible, preferred to intramuscular administration (IM). After a first injection of anti-D, if repetition of potential sensitizing events occurs, abstention of prophylaxis is possible depending on the previous administrated dose (protection lasts 6 weeks for 200microg and 9 weeks for 300microg) and the amount of feto-maternal hemorrhage. For routine prophylaxis of the third trimester, 300microg of anti-D should be proposed IM at 281+/-GW. Abstention of Rh prophylaxis is possible if the alleged father is certified RhD negative or if the fetal RhD genotype is confirmed negative. At delivery, RhD phenotype of the newborn should be determined even if RhD fetal genotype is known. Maternal blood should be drawn for quantification of feto-maternal transfusion at least 30 min after delivery is completed.
Blood Transfusion↗
[Text of the guidelines for prevention of fetomaternal rhesus-D allo-immunization].
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Female↗
[Alloimmunization to a high frequency Rh antigen].
We report the case of a pregnant woman sensitized with a panreactive anti-Rh17 alloantibody. Patient's red blood cells showed a partial deletion of Rh antigens, which was responsible for the alloimmunization. An autotransfusion program was instrumented so as to cover possible demands. Molecular analysis of the RH locus showed the presence of a hybrid RHCE-D(5-7)-CE allele that gave origin to the deleted phenotype.
Adult↗
[Prevention of Rh (D) alloimmunization in Rh (D) negative women in pregnancy and after birth of Rh (D) positive infant].
OBJECTIVE: The objective of this review was to assess the effects of antenatal anti-D immunoglobulin on the incidence of Rhesus D alloimmunization when given to Rh-negative women without anti-D antibodies and assess the effects of giving anti-D to Rhesus negative women, with no anti-D antibodies, who had given birth to a Rhesus positive infant. DESIGN: A review article. SETTING: Department of Obstetrics and Gynecology, Department of Medical Genetics and Fetal Medicine, University Hospital, Olomouc, Ministry of Health, Czech Republic. SUBJECT AND METHOD: We searched the Cochrane Pregnancy and Childbirth Group trials register, refence lists of relevant articles and bibliographies. CONCLUSION: The risk of Rhesus D alloimmunization during or immediately after a first pregnancy is about 1%. Administration of 100 microg (500 IU) anti-D to women in their first pregnancy can reduce this risk to about 0.2% without, to date, any adverse effects. Anti-D, given within 72 hours after childbirth, reduces the risk of RhD alloimmunization in Rhesus negative women who have given birth to a Rhesus positive infant. However the evidence on the optimal dose is limited.
Female↗
[Successful emergency treatment of a case with severe hemolytic disease of the newborn due to maternal Rh deletion phenotype-D].
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Adult↗
Serologic and molecular genetic management of a pregnancy complicated by anti-Rh18.
Antibodies, such as anti-Rh18 (Hr/Hr(S)), that react with the common products of RHCE can cause HDN as well as severe hemolytic transfusion reactions. Individuals with anti-Rh18 antibodies can have different RHCE genetic backgrounds; therefore, sera and RBCs from these individuals may cross-react. In these situations, genotyping may be the best method to determine compatibility. We report a 26-year-old pregnant Puerto Rican woman who presented at 31 weeks' gestation with anti-E and anti-Rh18 in her serum. No potential donors were identified among family members or within the American Rare Donor Program; therefore, a unit of the patient's RBCs was collected one week before her planned caesarian section. To improve our ability to supply blood for this patient in the future, molecular testing was performed. The patient was found to be homozygous for an RH haplotype in which a variant RHD*DAR, is linked to a variant RHCE*ceAR. The DAR-ceAR haplotype has been described in Dutch-African populations, but this is the first report of an individual self-identified of Hispanic ethnicity. This case report demonstrates the clinical importance of molecular testing of patients with rare Rh phenotypes.
ABO Blood-Group System↗
[Serological conflict: relation between antibody titer, Liley's zone and the condition of the fetus and newborn infant].
On the basis of analysis of 128 cases of serological incompatibility it was found that antibodies to Rh in titres of 1/8 or less constituted a good prognostic factor, and without evidence of fetal distress in USG examination this was not an indication to treatment undertaking. If the titre is from 1/16 to 1/128 the prognosis is worse and the degree of fetal haemolytic disease risk may be estimated on the basis of USG and Liley's zone. The prognosis is very bad in case of titre exceeding 1/128 and high Liley's zone, and without effective treatment of haemolytic disease in fetal life only few fetuses survive.
Erythroblastosis, Fetal↗
[Rational algorithm of primary Rhesus typing].
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Algorithms↗
[Revised definition of the concept rhesus-negative blood donor; practical experiences].
In 1987 the Central Medical Blood-transfusion Committee of the Netherlands Red Cross decided to modify their definition of 'Rh-negative' as it applied to blood donors. Until then the term Rh-negative had been reserved for donations that grouped as C- and E-negative and failed to react with IgG anti-D by the indirect antiglobulin test (IAT). From June 1987, however, donations were considered to be Rh-negative if they failed to react with two strong anti-D sera. An evaluation is presented over the first one and a half years of working with the new definition, the problems that were encountered and the measures that are taken to guarantee the quality of Rh testing.
Blood Banks↗
[Rh, Du phenotype in the pregnant woman].
The Rh, Du blood phenotype occurs rarely in the white population (0.23-0.60%). Its clinical significance is whether it should be considered it as Rh positive or negative. A pregnant woman with blood type Rh, Du (+), who delivered an Rh D (+) baby and was not given Rh immune globulin is presented. The Du antigen is manifested by weak expression of the D gene on the RBC envelope, and therefore Rh Du (+) is considered Rh (D) positive. An exception to this rule is the occurrence of transplacental fetomaternal bleeding in an Rh negative mother carrying an Rh positive fetus, when blood is typed close to the time of hemorrhage. In addition, there are other rare phenotypes, such as the D variant and the Du variant, in which there is alloanti-D present in the serum of Rh (D) positive or Rh Du positive patients, causing mild hemolytic disease of the newborn in rare instances.
Female↗