International Society of Blood Transfusion Working Party on red cell immunogenetics and blood group terminology: Cancun report (2012).

The International Society of Blood Transfusion Working Party on red cell immunogenetics and blood group terminology convened during the International congress in Cancun, July 2012. This report details the newly identified antigens in existing blood group systems and presents three new blood group systems.

Transfusion of rare cryopreserved red blood cell units stored at -80 degrees C: the French experience.

The technology allowing freezing of RBC units has been available for many decades. The high-glycerol method for RBC storage at -8 degrees C is predominantly used. Several studies have shown satisfactory results regarding the in vitro viability and function of cryopreserved RBCs. RBC freezing is nowadays mostly encountered in rare blood programs and military deployments. Preservation time of frozen RBCs appears to be virtually indefinite, but most countries apply a 10-year outdate. There is no mandatory time restriction in France. The National Rare Blood Bank currently includes 962 (17.5%) RBC units aged to years or more and 153 (2.8%) aged 20 years or more. Since 1994, 1957 RBC units have been thawed and transfused, among which 118 were aged 10 years or more and 8 were aged 20 years or more. Discarding RBC units older than to years may be highly sensitive for very rare blood groups, e.g., U-, of which approximately 30 percent of the cryopreserved units are aged to years or more. However, the lack of nucleic acid testing for HIV and HCV may be problematic for old RBC units drawn from donors who were not subsequently tested for these markers, which is now mandatory in most countries. Regarding the 118 transfused RBC units older than 10 years, no evidence of hemolysis of thawed RBCs and no transfusion reaction, clinical or biologic hemolysis, or transfusion ineffectiveness was reported, either by any of the parties involved in the transfusion supply of rare RBC units or through the French hemovigilance program, which requires a mandatory report of any transfusion reaction. It has recently been suggested to extend the 10-year restriction in some countries. Considering our experience and observational data, we may consider it safe and efficient to transfuse rare frozen RBC units older than 10 years. An international consensus for RBC cryopreservation time should ideally be established.

[Roles of an independent national Society of Blood Transfusion in the European Union]. / Rôles d'une société nationale de transfusion sanguine indépendante dans les pays de l'Union Européenne.

Learned societies are a reality in the medical sector. They are currently tending to become a federation of professionals, which targets are to secure the independence of training programs and perpetuate the scientific knowledge of blood transfusion. This is the way the French Society of Blood Transfusion (SFTS) built its role and scope of action in the service of patients.

[The red blood cell antigen terminologies]. / Les nomenclatures de groupes sanguins érythrocytaires.

Since the discovery of blood groups in humans, several hundred new red blood cell antigens have been identified. Multiple terminology modes have been used to denote each new antigen identified, but without any consistent rules, nor international consensus. This was largely due to the many discoverers of these antigens, using either letters of the alphabet, numbers, part of the patient or donor's name, place of discovery or animal names. Besides, alternative terminologies for the Rh system were implemented in the middle of the twentieth century (Rosenfield, Fisher-Race, Wiener). The International Society of Blood Transfusion described for the first time in 1980 the advantages of an alphanumeric and homogeneous nomenclature, keeping with the genetic bases of blood groups, as well as a classification of all RBC antigens within several families. A variant of this new terminology, exclusively numerical, was simultaneously established, mainly designed for computer data exchange. Nearly 30 years later, 308 red blood cell antigens are described within 30 systems, 12 collections, one 700 series and one 901 series of blood groups. Any person involved in the field of immuno-haematology must master both the usual and international nomenclatures. The Wiener nomenclature used for Rh haplotypes, still largely used today, is also important to be known. The systematic use of the international nomenclature should be strongly encouraged, either in the labelling of blood products, clinical laboratory reports or blood type cards.

[Genotyping of blood group systems at the CNRGS. I: FY, JK, MNS systems]. / Génotypage des systèmes de groupe sanguin d'intérêt transfusionnel au CNRGS. I: les systèmes FY, JK, MNS.

AIM OF THE STUDY: Determination of blood group antigens from data obtained by using molecular methods (genotyping) has become an indispensable tool in the specialized immunohematology laboratories. The French National Reference Centre for Blood group typing (CNRGS) routinely performs genotyping of the FY, JK and MNS system (common genotyping), providing a phenotype deduced from genotyping data for FY1, FY2, JK1, JK2, MNS3 and MNS4 antigens. PATIENTS AND METHODS: We performed a study to evaluate the common genotyping prescriptions referred to the CNRGS over the last three years. RESULTS: Between February 2006 and February 2009, the CNRGS performed 2392 genotyping, including 981 common genotyping. Analysis of 172 common genotyping performed in 2008 showed that 63.8% of the prescriptions expressed a genotyping demand. Of the latter, 42.7% were genotyping prescriptions only, whereas 57.2% were prescriptions of genotyping associated with alloantibody identification. All prescriptions refer to blood group genotyping indications issued from guidelines, with no incorrect prescription, that are patients transfused within four months before blood sampling in 63.6% of cases or a positive direct antiglobulin test in 24.5% of cases. Lastly, 36% of the blood samples referred to the CNRGS had no genotyping prescription. Yet, common genotyping was performed by the CNRGS to get complete immunohematology data for antibody identification. CONCLUSION: Usefulness of blood group genotyping in specialized immunohematology laboratories is obvious. However, the strategy for implementation of molecular methods remains to be defined. Use of high-throughput DNA analysis should change our way of working.

[The White Book]. / Le livre blanc.

It is necessary for European countries to have references and guidelines to cope with the wide field of blood transfusion. It is the institutions and professionals' role to provide for technical specifications linked to the collection, qualification, preparation, storage and distribution of labile blood products. In this context, EuroNet-TMS publishes every five year (2005, 2010...) a White Book meant to issue statements on the current situation, activities in progress in Europe and future developments.

[ABO-RH1 grouping and red blood cell antibody screening: error analysis in the French external quality assessment in 2006]. / Groupes sanguins et recherche des anticorps antiérythrocytaires: analyse d'erreurs au contrôle national de qualité en 2006.

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 rare blood groups: a public health challenge]. / Les phénotypes érythrocytaires rares: un enjeu de santé publique.

A rare blood group is usually defined as the absence of a high prevalence antigen or the absence of several antigens within a single blood group system, if its prevalence in France is 4/1000 or less in the general population. An individual with a rare blood phenotype can develop a naturally-occurring or immune antibody corresponding to his rare specificity. In case an extremely low stock of compatible blood is available at the national level, a so-called "transfusion deadlock" is described. Most of the individuals with a rare blood group are coincidently identified when a routine pretransfusion testing or pregnancy follow-up is performed, if the antibody(ies) corresponding to the rare specificity is(are) present. Other individuals are discovered following a systematic red cell typing, or family investigations in siblings. One hundred and twenty-one rare blood specificities and 42 rare blood genotypes are currently defined at the French National Reference Laboratory for Blood Groups (CNRGS-Paris). The French national registry of individuals with a rare blood phenotype/genotype includes about 9600 people, who are urged to regularly donate blood for the National Rare Blood Bank. This bank, based on a homologous blood transfusion program, is in charge of the long-term storage of rare frozen blood units, that can only be delivered after receiving authorization from the CNRGS. The global and individual care management of the individuals with a rare blood group, concerning potentially several hundred thousand people in France, requires a close cooperation between all the protagonists within the transfusion chain.

Blood components: current challenges.

Labile blood products are still here to stay for quite a long time. All European surveys come in agreement to reveal that indications, extremely heterogeneous from one country to another, are not fully under control. Both the EuroNet-TMS network and Euro'SAT congresses aim at improving the use of such products within an evidence-based medicine perspective.

[DNA typing: analysis of difficult cases]. / Les empreintes génétiques: des affaires d'interprétation difficile.

DNA fingerprinting is a tool to identify individual and allows to resolve many difficult cases. Their application fields are various: paternity or maternity testing, criminal affairs (crime, identity usurpation, identity substitution...). This review relates some interesting and atypical cases.

[Point about DNA profiling: technologies, applications, and legislation]. / Les empreintes génétiques: état de l'art en 2007, techniques, applications et législation.

Molecular biology progress in DNA fingerprinting has revolutionized forensic science. It's a reliable tool to identify an individual; it provides a true "genetic identity card". It's based of the concept that no two individuals can have an identical DNA pattern except identical twins. This article is a clarification on current technologies used in DNA profiling, their applications and its legislation, according a special place to the national databases (FNAEG), which is in great development for the moment.

[Red blood cell antibody screening: error analysis in a french interlaboratory comparison program survey]. / Recherche des anticorps antiérythrocytaires: analyse d'erreurs au Contrôle national de qualité

The French quality control is organized by the French Health Products Safety Agency. In 2005, the immuno-haematology testing control included the screening of an anti KEL 1 antibody. 17 out of 2639 laboratories (0,64%) answered 'negative screening'. All laboratories received a questionnaire in order to understand the failure. In this paper the authors present the detailed laboratories' responses and failure explanations.

[Impact of blood group antigens in transplantation]. / Influence des antigènes de groupes sanguins en transplantation.

Blood group antigens seem to be implied in the mechanisms of tissue and cell rejection. All erythrocyte blood groups are not only demonstrated on red cells. Some of them can be observed on several tissues of the body, particularly antigens of ABO, Hh, Lewis and I(i) systems... These ubiquitory antigens, called "histo-antigens" are developed very early at the various embryofetal stages depending on the tissues. The ABO system plays a fundamental role in graft and transplant. If the ABO compatibility is fundamental for the prognosis of a kidney, liver and heart transplantation, it has only a minor effect on the marrow, bone or cornea transplantation. The physiopathologic mechanisms are known, for the main points, and in connection with ABH antigens presence. Recent works show that systems RH, FY and JK could play a role in the process of graft rejection.

[The European network of transfusion medicine societies (EuroNet-TMS): The White Book 2005]. / Le réseau européen des sociétés de médecine transfusionnelle (EuroNet-TMS): Le Livre Blanc 2005.

Europe is building up. It develops in a quite complex environment, in which health care represents an important field of activities. As for blood transfusion, it plays a major role especially in the development of medical activities as well as for the patients treatments. Today, blood components are still of human origin and there are no substitutes for them. As a medical discipline, Blood Transfusion represents a broad field in medicine which requests the involvement of numerous actors. It is up to professional medical/scientific societies to promote the discipline. This is why it has been considered necessary and relevant to build up a federation of transfusion medicine societies throughout the European Union (EU) ; it is called EuroNet-TMS, the European Network of Transfusion Medicine Societies. This network groups more than 7500 professionals of involved in blood transfusion activities. It has six major objectives: 1) To find coherent responses to issues at stake in transfusion; 2) To promote medical and scientific developments of blood transfusion in Europe; 3) To ensure the highest and most up-to-date scientific level to meet safety and quality standards; 4) To offer similar services to all EU citizens in the field of blood transfusion; 5) To share knowledge and date within Europe; 6) To develop interfaces with decision-makers among the diverse European countries. The first step is the writing of the "White Book 2005" which reports the state of the art of blood transfusion in Europe; a prospective plan is proposed to be discussed.

[Cellular mechanisms implicated in anti-erythrocyte alloimmunization]. / L'allo-immunisation anti-érythrocytaire: mécanismes cellulaires.

In many clinical situations patients are dependent on blood transfusions. Occurrence of alloimmunization to blood group antigens (BGA) complicates the transfusion strategy and may be involved in clinical transfusion stalemate situations. B cell differentiation into antibody-secreting plasma cells is triggered by antigen and requires helper T cells which produce cytokines. Although antibodies implicated in BGA alloimmunization have been studied for many years, little is known about helper T cell responses that drive their production. Few studies on BGA specific T cell responses have been published today. This review summarizes the new developments in the field of cellular mechanisms implicated into antibody production. The definition of immunodominant peptides derived from RhD and Jk(a) BGAs, the cytokine patterns induced and the HLA class II molecules implicated in their presentation are analyzed. A tolerogenic route for RhD immunodominant peptides is experimented. Identification of such immunodominant peptides, the cytokine patterns induced and the HLA class II molecules implicated in their presentation, would facilitate the design of new therapeutic strategies including the specific control of alloimmunization with peptide antigen tolerogens or the ex-vivo induction of regulatory T cells.

[Foetomaternal erythrocyte incompatibilities: from immunohaematologic surveillance of pregnant women to haemolytic disease of the newborn]. / Incompatibilités foetomaternelles érythrocytaires (IFME): de la surveillance immunohématologique des femmes enceintes à la maladie hémolytique du nouveau-né (MHNN).

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.

[Annual Report 2004 - French National Reference Centre for Rare Blood Groups and Immunohaematology (CNRGS)]. / Rapport 2004 - Centre national de référence pour les groupes sanguins (CNRGS).

In 2004, the French Reference Centre for Rare Blood Groups and Immunohaematology (CNRGS) developed 7 types of activities: 1) Studies of complex Immunohaematology issues (IH), 2) Studies of rare blood phenotypes, 3) the transfusion of patients showing complex issues, 4) IH reactive control in consistency with the 98/79/CE European Directive, 5) European studies and expertise on reactives and techniques, 6) Biotechnologies applied to blood groups, in particular RH, KEL, FY, JK, DO and CO, 7) Implementation of allo-immunization research programs (cellular immunology and grafting issues). The CNRGS efficiency is based on the 'reference-research' link thanks to the Inserm partnership and direct applications to patients allowing to a better risk management and control.

[Theoretical risk management and legitimacy of the precautionary principle in medicine. Look back at HIV contamination through blood transfusion in France, twenty years ago]. / La gestion d'un risque potentiel et la légitimité du principe de précaution en médecine. Regard vingt ans après sur la contamination transfusionnelle par le VIH en France.

The precautionary principle first appeared in France during the health crisis following the contamination of patients with HIV via blood transfusion. This study analyses whether the risk associated with blood transfusion was taken into account early enough considering the context of scientific uncertainty between 1982 and 1985. The aim was to evaluate whether a precautionary principle was applied and whether it was relevant. First, we investigated the context of scientific uncertainty and controversies prevailing between 1982 and 1985. Then we analysed the attitude and decisions of the French authorities in this situation to determine whether a principle of precaution was applied. Finally, we explored the reasons at the origin of the delay in controlling the risk. Despite the scientific uncertainties associated with the potential risk of HIV contamination by transfusion in 1983, we found that a list of recommendations aiming to reduce this risk was published in June of that year. In the prevailing climate of uncertainty, these measures could be seen as precautionary. However, the recommended measures were not widely applied. Cultural, structural and economic factors hindered their implementation. Our analysis provides insight into the use of precautionary principle in the domain of blood transfusion and, more generally, medicine. It also sheds light on the expectations that health professionals should have of this principle. The aim of the precautionary principle is to manage rather than to reduce scientific uncertainty. The principle is not a futile search for zero risk. Rather, it is a principle for action allowing precautionary measures to be taken. However, we show that these measures must appear legitimate to be applied. This legitimacy requires an adapted decision-making process, involving all those concerned in the management of collective risks.