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Objective: To assess the potential impact of new guidelines recommending routine antenatal prophylaxis at 28 weeks of pregnancy on incidence, consequences and cost of rhesus immunization., Study Design: All rhesus immunizations of 224,500 ongoing pregnancies in two neighbouring administrative areas in France between 2000 and 2006 were enrolled in this retrospective study. To determine the aetiology of immunization and to specify when sensitization occurred, we searched sensitizing events between the last negative and the first positive red-cell antibody test results. Perinatal consequences and costing were also analyzed., Results: From 138 rhesus negative women bearing anti-D antibodies, none had received routine prophylaxis at 28 weeks. 37% were primary immunizations and 63% were reactivating former immunization. 63% sensitizations occurred after unprovoked foetal-maternal haemorrhage, mostly after 28 weeks (54%). Twenty-five (18.1%) sensitizations resulted from inappropriate management of existing prophylaxis. Immigrants with previously acquired antibodies accounted for 10% of cases. There was no foetal demise and none born before 28 weeks among our 140 babies. Only 25% required intensive care, mostly those born to mothers reactivating immunization, with an overall good perinatal outcome. Systematic 28-week prophylaxis would have cost about euro 2.5 million to reduce overall cost of immunizations by euro 0.6 million., Conclusions: The incidence of rhesus immunization in our population was low at 0.41 per thousand. Routine antenatal prophylaxis could have avoided 54% of these immunizations but expected perinatal benefits are low, as newborns with the worst issue were born to mothers with unavoidable immunizations. Therefore the cost-effectiveness of this strategy is doubtful.

Further to a survey set up in 2006 over 2600 laboratories by the French agency for health product safety (AFSSAPS), seven ABO grouping errors and 53 negative answers to red blood cell antibody screening with a serum containing anti-RH1 antibody, have been found. A questionnaire sent to the involved laboratories revealed non-analytical errors already met in previous cases. Besides, the analytical stage has also induced red blood cell antibody screening errors due to a wrong serum collection by the automat. Here are displayed the analysis of the questionnaire results and proposed corrections.

The RH blood group is the most polymorphic and immunogenic blood group system. The RH locus is composed of 2 highly homologous genes: the RHD gene encoding the D polypeptide; and the RHCE gene, encoding C or c together with either E or e polypeptides. Numerous variants exist for both RHD and RHCE genes. Among them we were interested in the serological and molecular definition of numerous pre-published RHCE variants encountered in different populations. The identification of these variants is crucial to ensure the transfusion safety for patients expressing these variants. Here we propose a procedure to identify some of them and discuss the adequate transfusion strategy. This procedure has enable us to identify new variants to be presented at the symposium.

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.

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.

Despite the generalization of prevention measures against foetomaternal alloimmunization with anti-D immunoprophylaxis since 1970s, retrospectively 30 years later, its complications (new-born child's severe haemolytic disease, foetal death by anemia or nuclear icterus by bilirubin encephalopathy) have not disappeared. At the same time, alloimmunizations against antigens other than D increase with no possible prevention. As part of the set up in France of regional files analysing and making an inventory of serious foetomaternal incompatibilities requiring in utero or neonatal transfusion, we felt the need to synthesize current data, biological profiles (early screening of erythrocytic alloimmunization and its follow up during pregnancy, father's immunohaematologic status, evaluation of in utero immune haemolysis and impact of new non invasive techniques of diagnosis-RH1 foetal genotypage from ADN foetal of RH1--mothers' maternal plasma), clinical and paraclinical data (evaluation of foetal haemolysis by echography, recording of foetal movements and foetal cardiac rhythm), therapeutic indicators (in utero foetal transfusions or exsanguinotransfusions, neo and postnatal transfusions or exsanguinotransfusions, induced premature labour, newborn's intensive continue phototherapy and Rhesus immunoprophylaxis) in order to enable medical and paramedical professionals to carry out the specific supervision of pregnancies with foetomaternal incompatibility, the in utero, neo- and postnatal treatment of child and the efficient therapeutic prevention of anti-D alloimmunization, in a cooperative way.

The French reference laboratory for rare blood groups (CNRGS) is working for all participants of the transfusion chain: from the donors to the recipients; from the French Establishment for Blood to medical laboratories; from hospital to the haemovigilance network; from governmental agencies to European structures. This laboratory is in charge of: (1) studies of complex problems of immunohaematology; (2) studies of rare blood group phenotypes; (3) reagents quality controls; (4) production of biological standards; (5) specific specimen banks; (6) molecular studies of blood group antigens and antibodies involved; (8) panels of reference cells or DNA; (9) international exchanges.

Objectives: In obstetrics, transfusion medicine is involved because of the risk of Rh isoimmunisation and of transfusion at delivery. In France, although these two situations have led to legal or professional recommendations, practices appear to be very different from one institution or one physician to another., Study Design: Retrospective study., Methods: A questionnaire using both direct questions and clinical cases was sent to all members of the French obstetric anaesthetists association (named CARO)., Results: One hundred and seventy-eight questionnaires (response rate 17.1%) were returned. Monitoring of anti-D antibody concentrations during pregnancy was performed in accordance with the legal recommendation (14/02/1992) in only 3.9% (Rh+) and 19% (Rh-) of women. Blood samples were performed either too often or too rarely in 39 to 72% of responses. At delivery, an immediate assessment of anti-D antibody concentration was required in almost 100% by the specialist on call in the blood bank while this measurement was considered necessary by only 80% of anaesthetists responding to the questionnaire. The distance between the maternity and the blood bank is greater than 14 km in 19% of responses and the largest time interval reported to obtain red cell concentrates was greater than 145 min in 18% of responses. Autologous blood transfusion is described as being used routinely in only 23% of responses., Conclusion: Significant failures in practice patterns and organisation of care are suggested by the responses to this questionnaire. This should stimulate a national debate to improve adequacy of practices to legal and professional recommendations and to review blood distribution to maternities in this country.

The French Blood Transfusion Society working group Immunohaematology and the French Blood Transfusion Center of Lille performed two quality control exercises-96-01 and 97-02-in order to evaluate identification performances of alloantibodies associated with an autoantibody recognizing a high frequency antigen. Concerning control 96-01, 83 (75%) of the 110 blood transfusion centers participating at this exercise sent results. The alloantibody screening was correct for 78 of them (94%). Sixty-one (78%) blood transfusion centers correctly identified the specificities (anti-RH1 + anti-FY1). Concerning control 97-02, 82 (94%) of the 87 blood transfusion centers participating in this exercise sent results. The alloantibody screening was correct for 69 (88%) of them. Fifty-three blood transfusion centers (77%) correctly identified the specificities (anti-RH3 + anti-FY1). These exercises allowed us to confirm the main procedures used in routine for national scale testing. The analysis of the results has underlined the importance of these tests for assessing the quality of these examinations, and highlighted the means to be carried out in order to improve them.

Until the '80s blood group reagents were composed of human or animal polyclonal antibodies; nowadays they are mainly produced from monoclonal antibodies. In this paper two aspects will be considered; firstly the evolution in the use of monoclonal reagents in France and secondly the quality of these new reagents in comparison with polyclonal reagents. From 1981 to 1995, 17567 batches of blood group reagents were analyzed and controlled by the French Blood Group Reference Laboratory (CNRGS). All data are given in six tables.