Iron deficiency among French whole-blood donors: first assessment and identification of predictive factors.

BACKGROUND: The objectives of this study are to estimate the prevalence of iron deficiency (ID) among French whole-blood (WB) donors to identify factors associated with ID and to generate decision trees. STUDY DESIGN AND METHODS: A prospective National multicentre study was performed on WB donors from March 11, to April 5th, 2019. Samples were selected randomly to perform serum ferritin. ID was defined as ferritin value under 26 ng/ml. All results were stratified by sex. Factors associated with ID were analysed using multivariate logistic regression model. CART algorithm was used for decision trees. RESULTS: Eleven thousand two hundred fifty eight WB donors were included. ID was more frequent in women (39·5%) than in men (18·0%). Among 7200 repeated donors, women below 50 yo had a higher risk (OR = 2·37; [1·97-2·85] IC95) than those above 50 yo. Factors associated with ID were: haemoglobin level under the threshold at donation n-1 except for women and n-2 donation; a low mean corpuscular haemoglobin at n-1 and n-2 donations; a shorter interval since n-1 donation and between n-1 and n-2 donations except for women; and women who had given three or four times in the last year. CART algorithm defined high risk of ID subgroups within three populations of donors, new female donors, repeated male donors and repeated female donors. In these identified subgroups, prevalence of ID was up to 72·1%. CONCLUSIONS: Our study showed the high prevalence of ID among French WB donors, identified well-known and new factors associated with ID and defined algorithms predicting ID in three populations.

Risk for Hepatitis E Virus Transmission by Solvent/Detergent-Treated Plasma.

Hepatitis E has emerged as a major transfusion-transmitted infectious risk. Two recipients of plasma from 2 lots (A and B) of pooled solvent/detergent-treated plasma were found to be infected by hepatitis E virus (HEV) that was determined to have been transmitted by the solvent/detergent-treated plasma. HEV RNA viral loads were 433 IU in lot A and 55 IU in lot B. Retrospective studies found that 100% (13/13) of evaluable lot A recipients versus 18% (3/17) of evaluable lot B recipients had been infected by HEV (p<0.001), albeit not necessarily at time of transfusion. Among evaluable recipients, 86% with a transfused HEV RNA load >50,000 IU were infected, most likely by the HEV-containing solvent/detergent-treated plasma, versus only 7% with a transfused HEV RNA load <50,000 IU (p<0.001). Overall, solvent/detergent-treated plasma might harbor HEV. Such an occurrence might result in a dose-dependent risk for transfusion-transmitted hepatitis E.

Donor-targeted serotherapy as a rescue therapy for steroid-resistant acute GVHD after HLA-mismatched kidney transplantation.

Acute graft-versus-host disease (GVHD) is a rare but frequently lethal complication after solid organ transplantation. GVHD occurs in unduly immunocompromised hosts but requires the escalation of immunosuppression, which does not discriminate between host and donor cells. In contrast, donor-targeted therapy would ideally mitigate graft-versus-host reactivity while sparing recipient immune functions. We report two children with end-stage renal disease and severe primary immune deficiency (Schimke syndrome) who developed severe steroid-resistant acute GVHD along with full and sustained donor T cell chimerism after isolated kidney transplantation. Facing a therapeutic dead end, we used a novel strategy based on the adoptive transfer of anti-HLA donor-specific antibodies (DSAs) through the transfusion of highly selected plasma. After approval by the appropriate regulatory authority, an urgent nationwide search was launched among more than 3800 registered blood donors with known anti-HLA sensitization. Adoptively transferred DSAs bound to and selectively depleted circulating donor T cells. The administration of DSA-rich plasma was well tolerated and notably did not induce antibody-mediated rejection of the renal allografts. Acute GVHD symptoms promptly resolved in one child. This report provides a proof of concept for a highly targeted novel therapeutic approach for solid organ transplantation-associated GVHD.

The evolving blood donor deferral policy for men who have sex with men: impact on the risk of HIV transmission by transfusion in France.

BACKGROUND: Blood donation deferral for men who have sex with men (MSM) in France was reduced from permanent to 12 months in July 2016. To inform a further reduction of the deferral period, an HIV risk assessment was conducted with two scenarios: S1, 4-month deferral; S2, 4-month deferral only in the case of more than one sexual partner (i.e., similar to other blood donors). METHODS: Baseline HIV residual risk (RR) was calculated from July 2016 to December 2017, using the Incidence Rate-Window Period method. The impact of both scenarios on RR was assessed using data from surveys on MSM and blood donors, to estimate 1) the number of additional MSM expected to donate in each scenario and 2) HIV incidence among these donors. RESULTS: Baseline HIV RR was estimated at 1 in 6,380,000 donations. For S1, an additional 733 MSM donors, and an additional 0.09 HIV-positive donations were estimated, yielding an unchanged RR of 1 in 6,300,000. For S2, these numbers were estimated at 3102 and 3.92, respectively, yielding an RR of 1 in 4,300,000. Sensitivity analyses showed that, under worst-case assumptions, the RR would equal 1 in 6,225,000 donations for S1 and 1 in 3,000,000 for S2. CONCLUSION: For both scenarios, the HIV RR remains very low. For S1, the risk is identical to the baseline RR. For S2, it is 1.5 times higher, and sensitivity analysis shows that this estimate is less robust than for S1. The French Minister of Health announced that S1 will be implemented in April 2020.

Seroprevalence of hepatitis E virus among blood donors on Corsica, France, 2017.

BackgroundHepatitis E virus (HEV) is an emerging zoonotic pathogen and an important cause of acute viral hepatitis in European countries. Corsica Island has been previously identified as a hyperendemic area for HEV.AimOur aim was to characterise the prevalence and titres of IgG antibodies to HEV among blood donors on Corsica and establish a model of the annual force of infection.MethodsBetween September 2017 and January 2018, 2,705 blood donations were tested for anti-HEV IgG using the Wantai HEV IgG enzyme immunoassay.ResultsThe overall seroprevalence was 56.1%. In multivariate analysis, seroprevalence was higher in men than in women (60.0% vs 52.2%; p < 0.01), increased with age and was significantly higher among donors born on Corsica (60.6% vs 53.2%; p < 0.01). No significant difference was observed between the five districts of the island. IgG anti-HEV titres were mostly low (70% of positive donors had titres < 3 IU/mL). In Corsican natives, increasing seroprevalence by age could be explained by models capturing a loss of immunity (annual probability of infection: 4.5%; duration of immunity: 55 years) or by age-specific probabilities of infection (3.8% for children, 1.3% for adults).ConclusionWe confirmed the high HEV seroprevalence on Corsica and identified three aspects that should be further explored: (i) the epidemiology in those younger than 18 years, (ii) common sources of contamination, in particular drinking water, that may explain the wide exposure of the population, and (iii) the actual protection afforded by the low IgG titres observed and the potential susceptibility to secondary HEV infection.

Hypersensitivity transfusion reactions to platelet concentrate: a retrospective analysis of the French hemovigilance network.

BACKGROUND: Among labile blood products, platelet concentrates (PCs) are the leading cause of hypersensitivity transfusion reactions (HTRs). These reactions often lead to interruption of PC transfusion and can result in a prolonged transfusion process leading to significant morbidity and use of premedication and close monitoring for patients with a history of allergic transfusion reactions. The French hemovigilance database is one of the largest standardized databases providing information on HTRs following administration of labile blood products. In this study, we analyzed this database to assess the relative risk of HTR for each type of PC. STUDY DESIGN AND METHODS: HTRs following PC transfusion were retrospectively extracted from the e-Fit Hemovigilance database of the French National Agency for Medicines and Health Products Safety (ANSM). Frequencies were calculated using the number of specific PCs transfused. RESULTS: Between 2008 and 2014, the overall estimated incidence of HTRs following PC administration was calculated at 232 HTRs per 100,000 PCs transfused. The rate of HTRs was significantly higher with apheresis PC (337/100,000) than with buffy-coat PC (94/100,000). Platelets in additive solutions (PAS) were associated with a significantly lower frequency of HTRs when compared with PCs in native plasma. Amotosalen/UVA- PCs (APCs and BCPCs) which are always in PAS in France, exhibited the lowest frequency of HTRs when compared with their corresponding PCs in native plasma or in PAS (p < 10-7 in all comparisons). CONCLUSION: Our results showed that the type of PC and its processing may have an impact on the risk of HTR.

Noncompliance with blood donor selection criteria - Complidon 2017, France.

BACKGROUND: Blood donor selection, consisting of a pre-donation questionnaire and interview, excludes potential donors who may be at risk of transfusion-transmissible infections. Assessing the reasons for noncompliance with blood donor selection criteria is important to maintain a high level of viral safety of blood products. STUDY DESIGN AND METHODS: An anonymous French online survey of a sample of blood donors (Complidon) was conducted from September to December 2017. Data were poststratified to be representative of all donors who donated blood between July 2016 and December 2017. RESULTS: Of 420,190 solicited donors, 108,386 completed the survey (26%). Overall, noncompliance was estimated at 5.6%. The least respected criteria regarded sex with more than one partner during the previous 4 months for donors (1.9%) and for donors' partners (1%), travel-related criteria (1.2%) and sex between men during the previous 12 months (0.73% of men). Reasons for noncompliance differed according to criteria. Donors who were non-compliant to sexuality-based criteria mainly said they did not want to be excluded or that the questions were too personal. Conversely, donors who were exclusively non-compliant to criteria other than sexuality-based criteria more often mentioned their non-compliance during the pre-donation interview but were nevertheless authorized to donate blood. CONCLUSION: Despite noncompliance to blood donor criteria being relatively low in France, it still represents a threat to blood safety. Accordingly, improved communication is important to ensure that donors fully understand each selection criterion and to emphasize to health professionals the importance of listening carefully without judging during pre-donation interviews.

Transfusion-Transmitted Hepatitis E Virus Infection in France.

There is growing concern regarding the risk of transfusion- transmitted (TT) hepatitis E. Since the first described case in 2006, several TT hepatitis E have been reported to the French hemovigilance network. We performed a retrospective analysis of all cases of TT hepatitis E reported between 2006 and 2016. Transfusion-transmitted hepatitis E with high imputability according to phylogenetic analysis occurred in 23 patients aged 8 to 88 years and involved mostly solid organ recipients (n = 9) or patients with malignant hematological diseases (n = 9, including 4 hematopoietic allograft recipients). Involved blood products were plasma (n = 7), among which 6 had undergone pathogen reduction with solvent/detergent (n = 4) or amotosalen + ultra-violet A (UVA) (n = 2 from 1 donation) treatments, red blood concentrates (n = 7), apheresis platelets concentrates (n = 3) and whole blood pooled platelets concentrates (n = 6), among which one had underwent amotosalen + UVA treatment. Median hepatitis E virus (HEV) RNA dose infused was 5.79 [4.36-10.10] log IU. HEV infection progressed to chronic hepatitis E in 14 (61%) immunocompromised patients, 2 of whom had advanced liver fibrosis at diagnosis. Chronic hepatitis E patients cleared HEV with ribavirin treatment (n = 10), after immunosuppressive drug reduction (n = 3), or spontaneously (n = 1). One additional organ transplant recipient with associated co-morbidities died with ongoing HEV infection and multiple organ failure. The other 8 (34.8%) patients with TT hepatitis E cleared HEV within 6 months with ribavirin treatment (n = 3), reduced immunosuppression (n = 1) or spontaneously (n = 4). Red cells, platelets, and plasma transfusions may be associated with TT hepatitis E that can evolve to chronic hepatitis E in immunocompromised patients. Hepatitis E virus has emerged in France as a clinically significant TT infection risk.

Transfusion of HIV-infected blood products despite highly sensitive nucleic acid testing.

BACKGROUND: In France, the risk of HIV transmission by transfusion was reduced by implementing pooled nucleic acid testing (NAT) in 2001 and individual NAT in 2010. We report here the first case in France of transfusion of human immunodeficiency virus (HIV)-infected blood donated during HIV pre-ramp-up phase that tested individual NAT negative. METHODS: Blood donations are screened for HIV antibodies and HIV RNA (ProcleixUltrio, Grifols; limit of detection at 95%, 23 copies/mL). When a repeat donor tests positive for HIV, a repository sample from the previous donation is tested with the Cobas Taqman HIV-1 test (CTM, Roche; limit of detection at 95%, 17 copies/mL). RESULTS: In August 2017, a 57-year-old male repeat donor was screened positive for HIV antibodies and RNA (plasma viral load, 11,599 copies/mL). The previous donation had tested negative with Ultrio in March 2017 but was positive with an unquantifiable plasma viral load when tested with CTM. Sequencing showed no mismatch between Ultrio primers/probes and the target sequence. HIV transmission was excluded by lookback studies in the recipient of platelets, which had been pathogen reduced, but not in the recipient of RBCs due to premature death. CONCLUSION: This case demonstrates that the risk of contaminated donations due to the early HIV infection phase going undetected by highly sensitive NAT is real but exceptional. The absence of transmission to the platelets recipient could be due to the very low viral inoculum and/or to the efficacy of the viral inactivation. This case also highlights the additional value of a systematic donation archiving and the importance of donor education and predonation selection.

An International Registry of Granulocyte Transfusions.

INTRODUCTION: Granulocyte transfusions are used to either treat or prevent life-threatening infections in neutropenic patients. Current evidence from clinical trials does not support or reject efficacy, nor guide practice. METHODS: A group of investigators have led the efforts to create an online registry to gather information on granulocyte transfusion practices from as broad a range of international settings. The data forms were adapted from an on-going study in England for electronic data management. Data is collected at the time of the request for granulocytes, weekly, at 28 days, and at 6 months. Information collected includes donor, granulocyte unit, patient and illness characteristics, and outcomes. RESULTS: The PROspective GRanulocyte usage and outcomEs Survey (ProGrES) is currently open for data entry. Centres across the UK have collected data on 80 subjects. Five institutions from 4 countries (2 from the US, 1 each from Brazil, and national services in Canada and France) are in the process of joining the study. Other countries have expressed interest. CONCLUSION: It is feasible to develop an international registry of granulocyte transfusions to characterise current practices and describe outcomes. This registry would provide a platform to explore the relationship between intervention and outcomes, and to generate evidence to inform granulocyte transfusion efficacy.

Hepatitis A: an epidemiological survey in blood donors, France 2015 to 2017.

Since mid-2016, hepatitis A virus (HAV) outbreaks, involving predominantly men who have sex with men (MSM), have affected countries in Europe and overseas. In France, HAV screening of blood donations in 2017 revealed a HAV-RNA prevalence ca fivefold higher than during 2015-16 (4.42/106 vs 0.86/106; p = 0.0005). In 2017, despite a higher male-to-female ratio (5.5 vs 0.7) and the identification of MSM-associated outbreak strains, only one of 11 infected male donors self-reported being a MSM.

[Organization of the transfusion supply chain]. / Organisation de la chaîne transfusionnelle.

Organization of the transfusion supply chain. The transfusion supply chain is a complete and complex organization starting at the marketing step followed by the blood drive preparation. The marketing is getting more and more important since donors move from the country to cities where the blood collection organization must be adapted to the citizen way of life. The collecting step and the pre-donation interview can now be done by trained nurses and nearly 20% are done so at present. Doctors are consulted in case of difficulties or adverse effects. The testing is centralized on only four laboratories in mainland France, highly automatized in order to treat 2 500 donations per day in a very short time. The processing of blood is done during that time and the labelling of blood products is possible at D+1. The products are distributed by the regional processing platforms to the delivery sites located near hospitals (156 delivery sites on the whole territory) and issuing for the patient is done by the immunohematology / delivery services of the EFS in 85% of the transfusion needs or by hospital blood banks in 15%. The security of the transfusion supply chain has clearly improved during the last decade, due to technical progress but also by a better training of the whole staff all along the chain.

Organisation de la chaîne transfusionnelle. La chaîne transfusionnelle est une organisation complexe et complète qui démarre par une étape de marketing qui guide l'organisation des collectes. Le marketing prend de plus en plus d'importance du fait des changements de société avec l'augmentation de la population citadine ou périurbaine et l'inévitable adaptation de la collecte à ces modes de vie. Lors de l'étape de collecte, les infirmier(e)s peuvent maintenant réaliser l'entretien pré-don, et ce sont presque 20 % des entretiens qui sont réalisés selon cette nouvelle modalité, le médecin restant en recours pour les cas difficiles et pour la prise en charge des malaises. La qualification biologique des dons est regroupée sur quatre plateformes de laboratoires en métropole. Ces laboratoires, très automatisés, traitent en moyenne 2 500 dons par jour, avec des délais de rendu de résultats courts qui permettent de libérer les produits à J+1. Pendant ce temps, les poches de sang sont préparées sur les plateaux régionaux de préparation et sont ensuite distribuées sur les 156 sites de distribution de l'Établissement français du sang (EFS). La délivrance nominative pour les patients est faite à 85 % par les services d'immunohématologie/délivrance de l'EFS et par les dépôts de délivrance ou d'urgence vitale des établissements de santé dans les 15 % des cas restants. La sécurité de toute la chaîne transfusionnelle s'est encore améliorée au cours de ces dix dernières années grâce aux progrès techniques mais aussi grâce à une meilleure formation continue de l'ensemble du personnel intervenant sur chacun des maillons de cette chaîne.

Type of plasma preparation used for plasma exchange and clinical outcome of adult patients with acquired idiopathic thrombotic thrombocytopenic purpura: a French retrospective multicenter cohort study.

BACKGROUND: Plasma exchange (PE) is the first-line therapy of acquired thrombotic thrombocytopenic purpura (TTP). Several plasma preparations have been available; their equivalence in terms of outcome remains uncertain. STUDY DESIGN AND METHODS: We performed a retrospective analysis of the cases prospectively reported from 2005 to 2010 to the national registry established by the thrombotic microangiopathies French reference center. We analyzed 108 initial episodes of acquired idiopathic TTP in adults treated with PE, 81 with solvent/detergent (S/D) plasma, and 27 with quarantine fresh-frozen plasma (qFFP). The primary endpoint was the time to platelet (PLT) count recovery. RESULTS: Time to PLT count recovery was not significantly different with S/D plasma versus qFFP (median, 15 days vs. 19 days, respectively; p = 0.126). Complete remission rates, exacerbations, and survival were comparable. By multivariate competitive risk (Fine-Gray) analysis, the only significant association with a shorter time to PLT count recovery was the absence of additional treatment (hazard ratio, 2.06; 95% confidence interval [CI], 1.39-3.05; p < 0.001). There was a significant interaction between type of plasma and age, and for patients less than 40 years old, the use of S/D plasma was associated with a shorter time to PLT count recovery versus qFFP (median, 13 [95% CI, 9-16] days vs. 20 [95% CI, 16-64] days, respectively; p = 0.004). CONCLUSION: The outcomes of acquired TTP treated with S/D plasma or qFFP seem similar and therefore both preparations can be used safely for PE in this indication. The faster response of S/D plasma observed in younger patients warrants confirmation in prospective studies.