[Transfusion transmitted bacterial infectious (TTBI) with blood component accountability score 2: Retrospective analysis of the French e-fit database 2000-2007. Groupe de travail­validation des IBTT (Working group for validation of transfusion-transmitted bacterial infections)]. / Les infections bactériennes transmises par transfusion avec imputabilité 2 du PSL : analyse rétrospective de la base e-FIT de 2000 à 2007.

PURPOSE OF THE STUDY: Transfusion transmitted bacterial infection is an adverse reaction occurring in a patient during blood transfusion and due to the presence of bacteria in the blood component. For each transfusion transmitted bacterial infection suspicion, clinical and biological investigations should allow to either affirm the accountability of the transfused product in the occurrence of the infection (accountability score 4) or exclude it (accountability score 0). However, among 60,175 adverse reaction sheets extracted from the French e-FIT database (AFSSAPS), 143 are classified as transfusion transmitted bacterial infection diagnosis and 97 of them show a score of accountability 2 (possible). This study aims to analyze these 97 adverse reaction sheets and search for the reasons that led the haemovigilance network actors not to refine the degree of accountability in line with an exclusion or a confirmation of transfusion origin. METHOD: During collective reading sessions, each adverse reaction sheet among the 97 extracted was re-analyzed with an accountability criteria grid, built beforehand, and proposed in the technical guide sheet for transfusion transmitted bacterial infection (e-Fit AFSSAPS). RESULTS: Among the 97 analyzed adverse reaction sheets with a score accountability of 2: 12.4 % were considered as "non-analysable"; 54% were reclassified in another diagnosis category: non haemolytic febrile reaction (n=12), unknown diagnosis (n=17); patient infection before transfusion (n=23); blood component's "smear" (n=9); retrograde contamination of blood component (n=5). Finally, only 18.5% adverse reaction sheets (n=18) were maintained with a true diagnosis of transfusion transmitted bacterial infection an accountability score of 2. These cases were in agreement with those described in number 2, 3 or 4 in the annex sheet "Fiche Technique TTBI". 70% of adverse reaction sheets reclassified under another diagnosis as transfusion transmitted bacterial infection had been declared between 2000 and 2004. In order to improve transfusion transmitted bacterial infection suspicions diagnosis approach and to guide the French haemovigilance network in the investigations following a transfusion transmitted bacterial infection suspicion, the group propose recommendations after each adverse reaction sheets category analysis. CONCLUSION: The improvement measures taken as part of the French haemovigilance declaration framework allowed to perfect the data quality of transfusion transmitted bacterial infection. Progresses are still to be made to improve clinical and biological declaration, in order to precise the accountability of a blood component in the occurrence of an adverse transfusion transmitted bacterial infection effect. Tracking transfusion transmitted bacterial infection notifications by a group of experts at the national level is still recommended.

[Adverse unidentified transfusion reactions in five French regions: analysis, results, propositions]. / Les effets indésirables receveurs inconnus de cinq régions françaises: analyse, résultats, propositions.

OBJECTIVE: Adverse transfusion effects with "unidentified diagnosis" are yearly notified on the French national database "e-FIT" in various numbers and with high interregional discrepancies. The aim of this work was to analyse them in order do reach a better understanding of these notifications. RESULTS: On a total of 2499 "Fiches d'Effets Indésirables Receveurs" (FEIR) registered in 2006 in five French regions, 416 with "unidentified diagnosis" were analysed. Fifty-seven percent of them were kept classified in "unidentified diagnosis". Forty-three per cent of FEIR were reclassified, some in already proposed diagnostic categories (100 EIR), some in new proposed diagnostic categories (80 EIR) as: pathological context of the patient, pains linked to transfusion, hypotension. CONCLUSION: The study confirms the necessity to re-examine the French notification system. It underlines the insufficiency of clinical and biological investigations, which could allow to reach accurate diagnosis. It gives prominence the necessity of taking into account the patient's pathology and targets at least two diagnoses of transfusion adverse effects which are not yet proposed on the FEIR model. This work brings an overture about evolution of the French haemovigilance database which will involve further developments.

[Haemovigilance in the health care establishment: its role in pediatric transfusion]. / Hémovigilance dans l'établissement de soins : son rôle en transfusion pédiatrique.

Haemovigilance, an important step in transfusion safety, had been set up by a French law in January 1993. Application of haemovigilance in public hospitals is based on three conditions: reporting of adverse transfusion events, traceability of blood products and prevention of adverse transfusion events. The implementation of haemovigilance follows the rules given in a Ministry order dated January 1994, the first of a series including regulations about patient information, virological follow-up of transfused patients, blood product distribution. Haemovigilance rules are the same for adults as for children, concerning blood product traceability and adverse event reporting. It is much more difficult in other fields such as autologous transfusion and "child-patient" information that depend on their parent advice and should be particularly adapted to the familial context, the type of disease and the treatment. Difficulties arise for completing pre- and post-transfusion, immuno-haematologic and virologic controls. Compliance to protocols, in agreement with blood banks, is necessary.

[Blood monitoring at the dawn of the 21st century]. / L'hémovigilance à l'aube du XXIe siècle.

A NEW DISCIPLINE: On January 4, 1993, the French parliament voted a law on Blood Transfusion Safety, creating a monitoring and warning system operating through a complex network and aimed at guaranteeing permanent efficacy, safety and efficiency of blood transfusion in France. A new discipline, blood monitoring was born. FUNDAMENTAL PRINCIPLES: Basically, blood monitoring is organized around two fundamental principles: blood products trackability from the donor to the recipient and mandatory reporting of all transfusion incidents. After a laborious development phase, the early results point out the immunological risk, particularly by ABO error, and the risk of bacterial contamination. AN EARLY WARNING SYSTEM: This blood monitoring system, whose primary purpose is to serve as an early warning device, must have the necessary tools to monitor, verify and analyze all available epidemiological data. Coordination of the blood monitoring system within the framework of the AFSSaPS (the French Agency for Sanitary Safety of Health Products) should enable it to fully reach this goal.

Limiting dilution analysis of human IL-2 producing T-cell precursors. Determination of hierarchical alloantigenic potential of human leukocyte antigens and evaluation of alloimune responses to single HLA-DP molecules.

Twenty nine healthy unrelated individuals were carefully selected and divided into three groups according to their HLA (Human Leukocyte Antigens) phenotypes. A sensitive and reproducible limiting dilution analysis (LDA) based bioassay using CTLL-20 cells for detection of human IL-2 was set up and used to assess the hierarchical impact of highly polymorphic HLA molecules on individual's alloreactivity. Our main interest was to evaluate the role of HLA-DP molecules in this process. By calculating frequencies of IL-2 producing helper T cell precursors (HTLp) and amounts of IL-2 produced in each experiment, we were able to confirm that HLA-DR molecules are the most potent alloantigens. In 29 different combinations where a single HLA-DP mismatch between stimulating and responding cells was evaluated, some were reasonably tolerant, while the other ones evoked moderate to relatively strong alloimmune responses. Finally, two groups with statistically significant difference in alloimmune responses to stimulating HLA-DP molecules carrying D,E,A,V or G,G,P,M amino acid sequences at positions 84,85,86 and 87 in the sixth variable region F of the molecule could be formed, according to HTLp frequencies and amounts of IL-2 detected. Data presented are of great importance for the selection of unrelated as well as related bone marrow donors for haematological patients.

Limiting dilution analysis of human IL-2 producing T-cell precursors. Determination of hierarchical alloantigenic potential of human leukocyte antigens and evaluation of alloimune responses to single HLA-DP molecules.

Twenty nine healthy unrelated individuals were carefully selected and divided into three groups according to their HLA (Human Leukocyte Antigens) phenotypes. A sensitive and reproducible limiting dilution analysis (LDA) based bioassay using CTLL-20 cells for detection of human IL-2 was set up and used to assess the hierarchical impact of highly polymorphic HLA molecules on individual's alloreactivity. Our main interest was to evaluate the role of HLA-DP molecules in this process. By calculating frequencies of IL-2 producing helper T cell precursors (HTLp) and amounts of IL-2 produced in each experiment, we were able to confirm that HLA-DR molecules are the most potent alloantigens. In 29 different combinations where a single HLA-DP mismatch between stimulating and responding cells was evaluated, some were reasonably tolerant, while the other ones evoked moderate to relatively strong alloimune responses. Finally, two groups with statistically significant difference in alloimune responses to stimulating HLA-DP molecules carrying D,E,A,V or G,G,P,M amino acid sequences at positions 84,85,86 and 87 in the sixth variable region F of the molecule could be formed, according to HTLp frequencies and amounts of IL-2 detected. Data presented are of great importance for the selection of unrelated as well as related bone marrow donors for haematological patients.