[The blood donors' haemovigilance in France]. / L'hémovigilance des donneurs de sang en France.

This work aim to present the descriptive analysis of serious adverse reactions in donors (dSAR's), which were notified in 2010 and 2011 in the French national haemovigilance database "e-FIT" (Internet secured haemovigilance reporting system). Some data, which are necessary for this analysis, also come from the regional haemovigilance coordinators' reports (RHC). The other parts of haemovigilance in the context of donation, without donors adverse reactions, such as post-donation information (PDI), adverse events occurred in the blood collection steps of the transfusion chain and epidemiology are not subject to this work analysis. This work shows that the quality of the data gradually improved since the setting up of the notification system of dSAR's. These data are particularly rich in learning lessons, but are still improving. It allows us to confirm that donor's safety, blood components quality, while preserving the blood components self-sufficiency in France, remains a priority. For these reasons, it is important to continue this haemovigilance awareness and to implement necessary actions that would be required for the protection of the donor's health and comfort during donation.

Overview of revised measures to prevent malaria transmission by blood transfusion in France.

Plasmodial transmission by blood donation is rare in non-endemic countries, but a very serious complication of blood transfusion. The French national blood service (Etablissement Français du Sang and Centre de Transfusion sanguine des Armees) intended to revise the measures to strengthen blood safety with regard to Plasmodiae as transmissible pathogens. To limit the risk of transmission during infusion, serious additive measures have been taken for more than a decade in France, which is the European country with the highest rate of exposure to imported plasmodial infections or malaria. These measures were revised and strengthened after the occurrence of a lethal transfusion-transmitted infection in 2002, but did not prevent another occurrence in 2006. This report examines the weaknesses of the systems and aims at emphasizing the safety measures already taken and addresses issues to best respond to that risk.

[Chagas disease: screening tests evaluation in a blood military center, prevalence in the French Army]. / La maladie de Chagas: évaluation des tests de dépistage au centre de transfusion sanguine des armées, prévalence dans les armées.

Chagas disease is a major public health problem in Latin and Central America, 15 to 20 million people are affected and some 100 million is at risk of acquiring Chagas disease. Chagas disease starts to appear in amazonian area and french Guyana. Three kits: Elisa Novagnost (Dade Behring), BioElisa Chagas (Orgentec) et Elisa Cruzi (BioMérieux) were compared using performance panel. Sensibility, reproductibility and specificity (using 40 serum of blood donors who never went to an endemic area) were evaluated. Orgentec assay (recombinant antigens) and BioMérieux assay (whole-epimastigote antigens) performed better than Dade Behring assay. The latter was discarded from the study at this stage. Lack of sensibility seems due to the antigenic composition. Reproductibility and specificity are good for the other two tests. Mixtures of recombinants antigens increased specificity, but sensibility is better using mixtures of whole-epimastigote antigens. For routine blood donor screening both tests must be performed. A prevalence study was done during 11 months on 1570 serum of military blood donors. Despite of a low prevalence (less than 0.7 per thousand), the entire donation from donors who were in the endemic area (7.95% from our whole population) are screened for antibody against Trypanosoma cruzi, with these two assays.

New approach to radiation burn treatment by dosimetry-guided surgery combined with autologous mesenchymal stem cell therapy.

The therapeutic management of severe radiation burns remains a challenging issue. Conventional surgical treatment (excision and skin autograft or rotation flap) often fails to prevent unpredictable and uncontrolled extension of the radiation necrotic process. We report here an innovative therapeutic strategy applied to the victim of a radiation accident (December 15, 2005) with an iridium gammagraphy radioactive source (192Ir, 3.3 TBq). The approach combined numerical dosimetry-guided surgery with cellular therapy using mesenchymal stem cells. A very severe buttock radiation burn (2000 Gy at the center of the skin surface lesion) of a 27-year-old Chilean victim was widely excised (10 cm in diameter) using a physical and anatomical dose reconstruction in order to better define the limit of the surgical excision in apparently healthy tissues. A secondary extension of the radiation necrosis led to a new excision of fibronecrotic tissues associated with a local cellular therapy using autologous expanded mesenchymal stem cells as a source of trophic factors to promote tissue regeneration. Bone marrow-derived mesenchymal stem cells were expanded according to a clinical-grade technique using closed culture devices and serum-free medium enriched in human platelet lysate. The clinical evolution (radiation pain and healing progression) was favorable and no recurrence of radiation inflammatory waves was observed during the 11 month patient's follow-up. This novel multidisciplinary therapeutic approach combining physical techniques, surgical procedures and cellular therapy with adult stem cells may be of clinical relevance for improving the medical management of severe localized irradiations. It may open new prospects in the field of radiotherapy complications.

[One case report of anti-JK1 antibody undetected on plasma sample]. / A propos d'un cas d'allo-immunisation anti-JK1 non dépisté sur plasma.

The sensitivity of the detection of irregular antibodies (DIA) is one of the fundamental bases of transfusion safety. Its implementation is specified in accordance with a very specific framework that allows the use of serum or plasma. The case reported here points out a failure to detect irregular antibodies in plasma sample. Thus a low intensity anti-JK1 antibody detected and identified in serum slipped through unnoticed in plasma. The difficulties to detect and identify this antibody, well-known as a deceptive and dangerous one, are being discussed in order to better assess the limitations of DIA.

CD127 expression and regulation are altered in the memory CD8 T cells of HIV-infected patients--reversal by highly active anti-retroviral therapy (HAART).

HIV infection activates abnormally the immune system and the chronic phase is accompanied by marked alterations in the CD8 compartment. The expression of CD127 (IL-7R alpha chain) by memory CD8 T lymphocytes in HIV-infected patients is analysed and reported. The memory CD8 T cell subset was characterized by expression of CD45RA and CD27 markers, and CD127 cell surface expression was measured ex vivo by four-colour flow cytometry. HIV infection was associated with a fall in the proportion of CD127(+) cells among memory CD8 lymphocytes that resulted in a higher CD127(-) CD45RA(-)CD27(+) CD8 T cell count in HIV-infected patients. Diminished CD127 cell surface expression [mean fluorescence intensity (MFI)] by positive cells was also observed in this subset. The data suggest that these defects were reversed by highly active anti-retroviral therapy (HAART). The regulation of CD127 expression was also studied in vitro. Down-regulation of CD127 by interleukin (IL)-7 was observed in memory CD8 lymphocytes from healthy donors and HAART patients. Expression of CD127 by memory CD8 lymphocytes cultured in the absence of IL-7 confirmed that IL-7R regulation is altered in viraemic patients. Under the same experimental conditions, memory CD8 lymphocytes from HAART patients were shown to express CD127 at levels comparable to cells from healthy individuals. Altered CD127 cell surface expression and defective CD127 regulation in the memory CD8 T lymphocytes of HIV-infected patients are potential mechanisms by which these cells may be impeded in their physiological response to endogenous IL-7 stimulatory signals. Our data suggest that these defects are reversed during the immune reconstitution that follows HAART.

[French training program for medical students in transfusion medicine. Transfusion Medicine Teachers' College]. / Programme en transfusion des étudiants en médecine. Collège des enseignants en transfusion sanguine.

In France, transfusion medicine training program has been updated. A national committee of professors in transfusion medicine propose a series of 13 items which represent the minimum knowledge that general practitioners should possess. This overview of transfusion medicine is far below the level that specialists should reach and they will need an additional specialized training. Several French universities have set up their own training program which is quite similar to the work of the committee of professors. The following recommendations are not strict guidelines but is a common basis which will be improved in 2005 according to new evidence based transfusion medicine.

[Blood transfusion security: one train may conceal another!]. / Sécurité transfusionnelle: un train peut en cacher un autre!

The discovery of antibodies with specificities that are directed toward antigens of high prevalence is a difficult situation to manage in emergency blood transfusion. The reactions they produce interfere with the identification of reactions due to other, clinically significant antibodies. We report a case which illustrates this problem in terms of transfusion safety and time to carry out the tests.

Quality assessment of seven types of fresh-frozen plasma leucoreduced by specific plasma filtration.

BACKGROUND AND OBJECTIVES: A study was undertaken to determine plasma quality after specific filtration. MATERIALS AND METHODS: Seven types of plasma were tested, after filtration of plasma from filtered or non-filtered whole blood. Leucocyte counting was carried out after a 30-fold concentration of the sample. Twenty-nine parameters (including coagulation testing, proteins, coagulation factors and activation markers) were measured before and after filtration, and after 6 months of storage. RESULTS: After specific plasma filtration, the average residual leucocyte counts were less than 2250/l. In spite of small statistically significant changes in proteins, coagulation factors and complement activation, this study showed that plasma filtration did not alter plasma quality. After 6 months of storage at -30 degrees C, factor VIII recovery varied between 91 and 109%. Haemostasis parameters and activation markers remained within the normal range. CONCLUSIONS: Specific plasma filtration reduced the leucocyte number to < 104 leucocytes/l. The quality of plasma was not altered by the additional step of specific plasma filtration.

[Comparison of techniques used to screen blood donations for malaria antibodies]. / Comparaison de techniques de dépistage des anticorps antipaludiques utilisées en transfusion.

In France all but one of the serological tests used to screen blood donations rely on ELISA-based techniques. The exception is malaria antibody detection that is performed by the indirect fluorescent antibody technique using commercially available kits. The reagent kit used at the French Army Blood Bank (FABB) is Falciparum-Spot IF (bioMerieux). However since the antigens in this kit are obtained from group A1 red blood cell cultures, false positive results can occur due to binding of natural antiglobulins. Over a 10-month period at the FABB, we disqualified a total of 55 donations (5.02% of total donations) because of positive Falciparum-Spot IF@1000 test results. Most disqualified donations (84%) involved donations with group O red blood cells. In the present retrospective study, these 55 disqualified donations were used to compare the specificity of three other serological tests used for detection of malaria antibodies: Falciparum-SpotIF after elimination of natural antiglobulins by absorption and neutralization with Witebski reagent and Paludix (Diagast). Use of all three techniques provided a specificity gain of over 87% but elimination using Witebski reagent led to a loss of sensitivity. At the FABB we have been using the Falciparum-Spot IF kit after elimination of natural antiglobulins since April 2001. Only 1.62% of donations tested have been disqualified due to the presence of malaria antibodies including 52% with group O red blood cells.

[Transfusional record and blood grouping methods: essential factors of transfusion safety]. / Dossier transfusionnel et techniques de groupage sanguin: éléments essentiels de la sécurité transfusionnelle.

The clinical and biological control of the whole transfusion process is a major preoccupation for everyone dealing with blood transfusion. Specially when the patient is a female recipient or belongs to a group with a high prevalence of alloimmunisation. This case report points out the outstanding importance of the immune compatibility, which must be strongly maintained to prevent any harmful consequences. The transfusional record transmission and a simple and sensitive blood grouping test are essential to increase transfusion safety.

[Specificity of immunofluorescent methods detecting malarial antibodies: comparative study in the screening of blood donations]. / Spécificité des techniques sérologiques de dépistage des anticorps anti-paludéens en immunofluorescence: étude comparative dans la pratique de qualification du don de sang.

UNLABELLED: In France, no case of transfusion-transmitted malaria has been reported since 1994, reflecting the efficiency of the blood donations screening. However, an insufficiently specific serological assay leads to an unjustified loss of red cell units. MATERIALS AND METHODS: A retrospective study included 55 sera previously disqualified for the presence of malarial antibodies. We used different assays detecting these antibodies: Paludix, Falciparum-Spot without or with the elimination of natural antiglobulins by two different methods. RESULTS: Using Paludix, 87% of sera were negative (P < 0.001). With the sera treated for the elimination of natural antiglobulins by neutralisation or absorption, Falciparum-Spot(TM) gave respectively 87% and 94.5% of negative results. CONCLUSION: When using assays avoiding non-specific fluorescence, the number of false positive results significantly decreased. Because the number of blood donors travelling in at-risk countries is continuously rising, a sufficiently specific method to detect malarial antibodies should save a lot of red cell units.

[Fall in the seroprevalence of hepatitis A in French youth]. / Effondrement de la séroprévalence de l'hépatite virale A chez les jeunes français.

OBJECTIVE: An anti-hepatitis A virus seroprevalence survey was performed in 1997 in 1052 French army recruits (mean age: 21.2 years). To describe epidemiological trends, the current pattern was compared to previous results obtained by similar methods in 1985, 1990 and 1993. RESULTS: In 1997, overall anti-hepatitis A virus seroprevalence was 11.5%. The greatest risk factor of hepatitis A infection was related to travel in intermediate or highly endemic areas for hepatitis A virus: 46% of overseas residents (odds ratio = 10.3), 28% of recruits who had travelled in developing countries (odds ratio = 3.7) and 7.65% of French living in industrialised countries are anti-hepatitis A virus antibody positive. Moreover, seroprevalence was higher in subjects with a history of icteria (adjusted odds ratio = 3.5) and families with at least 3 children (adjusted odds ratio = 3). No association was found with drinking water, socioeconomic status such as baccalaureat degree, or parents profession. The seroepidemiological shift of hepatitis A, as assessed in three previous studies, shows a marked decrease of 20% in 12 years from 30.4% in 1985, to 21.3% in 1990, to 16.3% in 1993, and to 11.5% in 1997. The decrease in the prevalence of anti-hepatitis A virus was more marked in young adults who had never travelled in endemic countries (decrease of 20%) than those who had visited or lived in developing countries (decrease of 10%). CONCLUSION: Although France is not highly endemic for hepatitis A thanks to improved hygiene and housing conditions over the past 20 years, a pattern of intermediate endemicity was seen in French overseas areas in which the risk of outbreaks of hepatitis A was higher. The decrease in anti-hepatitis A virus seroprevalence in French youth can be used to draft a public health policy for hepatitis A control.

Regulatory dysfunction of the interleukin-2 receptor during HIV infection and the impact of triple combination therapy.

The interleukin-2 (IL-2)/IL-2 receptor (IL-2R) system is the main regulatory determinant of T cell reactivity. Although it is well known that IL-2 secretion is impaired during HIV infection, up to now IL-2R expression has not been extensively studied in HIV-infected patients despite the use of IL-2 in clinical therapy trials. We show here that IL-2R expression in HIV patients with high viral load (group 1 in the study) is greatly enhanced on B lymphocytes, CD8 T lymphocytes, and monocytes, but not on CD4 T lymphocytes, compared with noninfected individuals. Paradoxically, this modified IL-2R expression does not lead to increased IL-2 responsiveness, except for B lymphocytes. In patients receiving triple combination therapy (TCT, two reverse transcriptase inhibitors and one protease inhibitor) that has triggered a drastic reduction in plasma viral load and an increase in CD4 counts (group 2 patients), IL-2R expression is significantly lower than in group 1 patients. Moreover, cells involved in cellular immunity and CD4 T lymphocytes have the capacity to respond to IL-2 after TCT. These results allow us to anticipate a beneficial role of IL-2 immunotherapy in combination with TCT.

Further analysis of interleukin-2 receptor subunit expression on the different human peripheral blood mononuclear cell subsets.

We have investigated the expression of the three components of the interleukin-2 receptor (IL-2Ralpha, IL-2Rbeta, and IL-2Rgamma) on the surface of the various peripheral blood mononuclear cell (PBMC) subsets by flow cytometry analysis. The PBMC were immediately isolated (ficoll) from blood collected on heparin as anticoagulant. The three IL-2R components are absent or only marginally detectable on CD4 T lymphocytes. No expression of the IL-2R chains is found for the B lymphocytes. In most donors, the three chains are not detectable on CD8 T lymphocytes, but for a few of them, IL-2Rbeta or IL-2Rgamma are clearly expressed. CD56 high (IL-2Ralpha+) and CD56 low (IL-2Ralpha-) natural killer (NK) cells express IL-2Rbeta, but not IL-2Rgamma. IL-2Rgamma is expressed by monocytes of all donors although with variable intensity. When blood is collected on other anticoagulants or when cells are isolated 1 day after collection, IL-2Ralpha, IL-2Rbeta, and IL-2Rgamma are largely expressed on the surface of most PBMC. This observation provides a possible explanation for divergent data previously reported on IL-2R expression. Finally, we show that IL-2Rgamma, which is not detectable on the cell surface of lymphocytes, is nevertheless expressed and stored as an intracellular component. This result is in agreement with the constitutive expression of the IL-2Rgamma gene and suggests a specific regulatory mechanism for IL-2Rgamma membrane translocation.

[Results of ultrasonographic and cytologic follow-up of 311 initially non-suspicious thyroid nodules]. / Résultats de la surveillance échographique et cytologique de 311 nodules thyroïdiens initialement non suspects.

The follow-up of initially non suspect thyroid nodules after fine needle biopsy is not completely worked out. Since 1985, we have entered upon a prospective study concerning the followup of thyroid nodules supposed to be benign after initial evaluation. What are the nature and the frequency of means to be used for their follow-up? Three hundred and eleven nodules are followed up on a mean duration of 2.44 years. The follow-up of 65 of them is 4 years or more. The follow-up of 120 others is 3 to 4 years; 197 nodules are followed up during 2 to 3 years. A physical examination, an ultrasonography completed with a fine needle biopsy or an ultrasonically guided fine needle biopsy are worked out every year. Twenty-three per cent of initial biopsies are non significant and 90% of them are ultrasonically guided biopsies. At the end of the study, the repeating biopsies reduce to 6% the non significant biopsies ratio. Four histological thyroid cancers are detected in three female patients 1 year, 2 years and 5 years after the initial evaluation. Ultrasound alterations of nodules are observed in case of very suspect biopsies. Ninety-six per cent of the followed up thyroid nodules remain not cytologically suspect. These findings allow us to propose the following guidelines for the assessment of a non suspect thyroid nodule: half-yearly or yearly physical examination, yearly or biennial ultrasonography, repeat biopsy after 2 or 3 years when clinical or ultrasound suspect modification is wanting.