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Anti-Rh32 causing severe hemolytic disease of the newborn.

A case of severe hemolytic disease of the newborn due to anti-Rh32 (R = N) is described. The infant recovered without any evidence of neurologic defects, following one exchange transfusion and phototherapy. Using commercial antisera, very weak reactions with anti-Rh2(C) and apparently normal reactions with anti-Rh5(e) were found in the family members carrying the R = N gene complex. However titrations with individual antisera revealed a weakened expression of the Rh5(e) antigen, albeit to a lesser extent than the Rh2(C). It is felt that the serologic findings are due to the fact that the R = N haplotype was paired with an Rh gene carrying normal amounts of Rh4(c) and Rh5(e) antigens. In addition, the maternal anti-Rh32 appears to be pure.

Adolescent↗

[HTLV1 infection and pregnancy].

OBJECTIVE: We report an epidemiological study with an analysis of the risk factors of the HTLV-1 seroprevalence in pregnant women and their children in the town of St Laurent du Maroni, French Guyana. MATERIAL AND METHOD: HTLV-1 seroprevalence and risk associated factors were first studied in all the pregnant women having delivered at St. Laurent between July 1991 and June 1993. Then, a retrospective analysis was performed in the children, aged between 18 months and 12 years old, born from HTLV-1 infected mothers, focusing especially on the duration of breast feeding and the level of HTLV-1 anti body titers and proviral load. RESULTS: The global HTLV-1 seroprevalence was 4.4% (75/1727) but it was more prevalent among ethnic groups of African origin such as the Noir Marron population (5.5%) and Haitians (6.3%). In the Noir-Marron population, which represents 70% of the studied population, HTLV-1 seropositivity was associated with a maternal age of>35 years, prior miscarriage, prior cesarean section, parity>4, gravidity>6 and negative rhesus factor. After logistic regression, HTLV-1 seropositivity remained associated with gravidity>6 and negative rhesus factor. Out of the 216 children born from 81 HTLV-1 infected mothers, only 21 were found to be HTLV-1 seropositive, giving a crude HTLV-1 transmission rate of 9.7% while among the 180 breast-fed children 10.6% were HTLV-1 seropositive. HTLV-1 seropositivity in children was associated with elevated maternal anti HTLV-1 antibody titer, high maternal HTLV-1 proviral load and child's gender, girls being more frequently HTLV-1 infected than boys. CONCLUSION: HTLV-1 infection, which can be responsible for severe pathologies in adults (adult T cell leukemia and tropical spastic paraparesis/HTLV-1 associated myelopathy) should be screened during pregnancy in women originating from high HTLV-1 endemic areas, as for France, mainly the French West Indies, French Guyana and Intertropical Africa. In case of HTLV-1 seropositivity, mothers should be informed on the risk of transmission and promotion of bottle feeding of their children should be strongly proposed.

Adult↗

Association of fetal and maternal carboxyhemoglobin levels in normal and Rh-alloimmune pregnancies.

OBJECTIVE: To compare paired antepartum fetal/maternal COHb ratios in whole blood from control and alloimmunized pregnancies and to examine the relationships between fetal and maternal COHb. METHODS: COHb levels were measured in paired fetal and maternal blood samples obtained at cordocentesis in 47 control and 16 Rh-alloimmunized pregnancies. COHb was determined by gas chromatography. Results were analyzed by t-test, regression and analysis of covariance. RESULTS: Although fetal/maternal COHb ratios for control and alloimmunized pregnancies were not statistically significantly different, i.e. 1. 11+/-0.04 and 1.26+/-0.09, respectively (P=0.09), fetal COHb levels were higher in Rh-alloimmunized fetuses (P=0.0002). Fetal COHb levels were also higher than paired maternal levels among the alloimmunized group (P=0.011), but not among the control group (1. 04+/-0.04, P=ns). In univariate regression analysis, fetal and maternal COHb levels were significantly correlated with one another in both control (r=0.52, P=0.0002) and alloimmunized pregnancy groups (r=0.52, P=0.05). Comparison of the slopes of the fetal versus maternal COHb plots for the two groups showed a significant difference (P=0.02), with the alloimmunized group having the steeper slope. CONCLUSION: Differences in the antepartum fetal-maternal COHb relationships in control and alloimmunized groups likely reflect increased endogenous CO production among alloimmunized fetuses as a result of pathologic hemolysis.

Adult↗

Characterisation of a chromatographically produced anti-D immunoglobulin product.

A chromatographic fractionation method has been developed for the production of a liquid-stable anti-D immunoglobulin product for intravenous and intramuscular use. An immunoglobulin fraction, highly enriched with anti-D immunoglobulins, was isolated by cation-exchange column chromatography and further polished, first by anion-exchange chromatography, followed by an aluminium hydroxide gel treatment. The process includes two specific steps for virus inactivation and removal, namely S/D treatment and nanofiltration. The overall anti-D process yield is about 56%. The final product is stabilised with human albumin and glycine and placed in ready-to-use syringes. The anti-D product was shown to be stable in liquid state for at least 30 months at 4 degrees C.

Chemical Fractionation↗

New approaches in the treatment of haemolytic disease of the fetus.

The incidence of Rh haemolytic disease of the fetus and newborn complicating pregnancy has fallen since the implementation of prophylaxis with Rh immune globulin. However, occasional mismatched blood transfusions and ineffective or inadequate prophylaxis still result in a few Rh-alloimmunized patients requiring treatment during pregnancy. The development of a safe technique for obtaining pure fetal blood samples has provided the opportunity to assess correctly the severity of anaemia and to study fetal haematology and biochemical parameters, and hence to gain a better understanding of the pathophysiology of this condition. The aim of antenatal management is to predict whether or not the fetus is severely affected, to correct fetal anaemia and to deliver the baby at the optimal time. Fetal IVT is the standard treatment in severe Rh alloimmunization in many centres. However, high volume transfusion without overloading the fetal circulation, as well as increasing the interval between transfusions without jeopardizing the fetal condition, can be achieved by a combination of IVT and IPT. Thus, the total number of transfusions needed and the overall procedure-related risk for each fetus is reduced. With the recent advances in fetal medicine, haematology and neonatology, the survival rate of affected fetuses in some centres is now about 90%. Fetal death will continue to be associated with two sets of circumstances: trauma or complications due to IVT or IPT in early gestation when delivery is not feasible, and late referrals with such severe hydrops that its reversal is not possible. There is still, therefore, a need for research into new methods of treatment, such as high dose intravenous IgG, which can non-invasively diminish fetal red cell destruction.

Blood Grouping and Crossmatching↗

Risks of chorion villus sampling.

From the experience accumulated in less than 4 years of chorionic villus sampling activity, much has been learned about the advantages of prenatal diagnosis in the first trimester. The safety of the procedure during this developmental stage has been extremely good. The record in this centre with over 2700 cases sampled and over 2000 deliveries has demonstrated a fetal loss rate similar to that observed in amniocentesis studies. It appears that fetal loss that may be attributed to the procedure is not more than 1% and may be less. Some of that loss appears to be correlated with avoidable trauma to the chorionic membrane area. If this conclusion is valid, then avoidance of this pattern even in the occasional difficult case may further improve the already acceptable safety record of the procedure.

Biopsy, Needle↗

Recombinant monoclonal antibody technology.

With the development of murine hybridoma technology over a quarter century ago, the ability to produce large quantities of well-characterized monoclonal antibody preparations revolutionized diagnostic and therapeutic medicine. For many applications in transfusion medicine, however, the production of serological reagents in mice has certain biological limitations relating to the difficulty in obtaining murine monoclonal antibodies specific for many human blood group antigens. Furthermore, for therapeutic purposes, the efficacy of murine-derived immunoglobulin preparations is limited by the induction of anti-mouse immune responses. Technical difficulties inherent in human hybridoma formation have led to novel molecular approaches that facilitate the isolation and production of human antibodies without the need for B-cell transformation, tissue culture, or even immunized individuals. These technologies, referred to as 'repertoire cloning' or 'Fab/phage display', involve the rapid cloning of immunoglobulin gene segments to create immune libraries from which antibodies with desired specificities can be selected. The use of such recombinant methods in transfusion medicine is anticipated to play an important role in the development and production of renewable supplies of low-cost reagents for diagnostic and therapeutic applications.

Animals↗

[Transfusion and alloimmunization in sickle cell anemia patients].

Transfusion therapy for sickle cell anemia is limited by the development of antibodies to red cell antigens. The aim of this study was to evaluate whether transfusion of blood matched for antigens Rh and Kell would reduce the incidence of alloimmunization. We determined the transfusion history, red cell phenotype and development of alloantibodies in 173 patients with sickle all anemia who received transfusions. Forty nine patients were transfused exclusively with frozen red blood cells (RBL) matched for antigens Rh and Kell; the rate of alloimmunization was 8.2%; antibodies to the Jkb, Jka, Fya and S were developed; 1 patient developed 2 antibodies. In a control group of 124 patients who received standard red blood cells, the rate of alloimmunization was significantly increased to 30.6% (p < 0.05); antibodies against C, E, K, Fya were the most frequently developed and 19 patients (16%) developed antibodies reacting with different antigens. In the 2 groups, alloimmunization occurred after receiving a significantly different number of transfusions: mean 9 in the patients transfused with matched RBC and 32 in the control group. The influence of the kinetics of transfusion was not demonstrated. To assess the effect that racial differences might have on alloimmunization, comparison of the red cell phenotype of patients with that of a panel of unselected blood bank donors was performed: the patients had a significant decrease in the frequency of red cell antigens corresponding to most of the detected alloantibodies JkB, C, S. Fyb, Fya and Kell.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Monoclonal anti-D for prophylaxis of RhD haemolytic disease of the newborn.

The incidence of Rh D haemolytic disease of the fetus and newborn has been dramatically reduced by the prophylactic administration of anti-D immunoglobulin to Rh D-negative women. This preventive treatment depends on adequate supplies of anti-D derived from plasma of immunised donors, and replacement with monoclonal anti-D would be advantageous. Two monoclonal antibodies, BRAD-3 (IgG3) and BRAD-5 (IgG1) have been produced from EBV-transformed B-lymphoblastoid cell lines in Bristol and extensively characterised. Both have shown good (but differing) functional activities, determined by study of interactions of anti-D coated red cells with effector cells bearing IgG Fc receptors. Phase I clinical trials using Rh D negative male volunteers were undertaken in Bristol. The plasma half lives of BRAD-3 and BRAD-5 were characteristic for their IgG subclass, and both anti-D mediated accelerated circulatory clearance of D-positive red cells infused two days after i.m. injection of the antibodies. BRAD-3 and BRAD-5 were then shown to protect the volunteers from mounting a primary anti-D response to these D-positive red cells, and thus they may be suitable for Rh D prophylaxis of Rh D-negative women.

Adult↗

Anti-D immunoglobulin in Rh(D) negative volunteers: clearance of Rh(D) positive red cells and kinetics of serum anti-D levels.

Properties of a new anti-D immunoglobulin were assessed in Rh(D) negative healthy male adults. Six volunteers received intravenous, and five volunteers intramuscular injections of 200 micrograms anti-D, 48 hours after pre-treatment with 5 mL of Rh(D) positive erythrocytes. Immediately after intravenous administration of anti-D, a rapid decrease of the Rh(D) positive erythroyctes was noted. After intramuscular injection of anti-D, there was a lag phase of 6 hours until the erythrocytes decreased, and the elimination rate was slower. Twenty-four hours after injection of anti-D, the Rh(D) positive erythrocytes were at the detection limit or no longer detectable in all volunteers. After intravenous administration, anti-D serum levels decreased from 45 ng/mL at 2 hours to 29 ng/mL at 24 hours, whereas after intramuscular administration, anti-D became detectable at 4 hours and increased to 11 ng/mL at 24 hours. During subsequent months, anti-D serum levels decreased at similar rates in both groups. After six months, anti-D was not detectable in any of the volunteers. Thus, the new anti-D immunoglobulin induced elimination of the Rh(D) positive erythrocytes and suggested that Rh(D) immunization of the volunteers was prevented.

Adult↗

[Contribution of hemovigilance to immunologic safety of blood transfusions: assessment after 3 years].

The haemovigilance system has indirectly introduced three types of information: a more precise tally of accidents and risks (even if the total number of events remains difficult to assess); an evolution of the mode of collecting relevant information (even if, after 3 years, it has become important to define new objectives and collection procedures); the identification of the main causes of errors leading to immunological accidents allowing the elaboration of schemes pointing out the possible failures and critical points of the various processes, such as blood bag distribution, ABO control at bedside, the prescription of examinations prior to transfusion. The analysis of haemovigilance data has induced a number of important consequences, particularly clinical practitioners' awareness of blood transfusion risks; elaboration of reliable and documented tools for the training of professionals and the information of patients; implementation of corrective and preventive measures, particularly to reduce accidents due to ABO incompatibility. These haemovigilance data will provide more fruitful results when cross-analysed with data from the reactovigilance system which is being set up. Until then, they will largely be used to elaborate blood transfusion quality assurance standards.

ABO Blood-Group System↗