Human immunodeficiency virus, hepatitis C virus and hepatitis B virus incidence in blood donors from 2000 to 2020 in France: Trends and lessons from haemovigilance surveillance.

BACKGROUND AND OBJECTIVES: Data from 21 years (2000-2020) of haemovigilance were used to assess human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) incidence rates in repeat blood donors and the occurrence of transfusion-transmitted (TT) viral infections. MATERIALS AND METHODS: Blood donors who converted for HIV, HCV or HBV markers within serial three-year analysis periods were included. Epidemiological and virological data were retrieved from the national epidemiological donor database and were supplemented with information on blood components and the infection status of recipients of the previous negative donation (D.N-1) of donors who seroconverted. RESULTS: Incidence rates declined from 1.27 to 0.35/100,000 person-years for HIV, from 0.59 to 0.19 for HCV and from 1.66 to 0.18 for HBV. Risk factors and lookback for 232 HIV, 90 HCV and 74 HBV seroconversions were investigated. The main risk factor identified at post-donation interview was having sex with men (47.8% of males) for HIV and a sexual risk for HCV (30.6%) and HBV (37.1%). The viral loads and sequences were retrospectively tested in 191 HIV, 74 HCV and 62 HBV D.N-1 archived samples. Six (five HBV and one HIV-1) were positive all low viral loads. Two recipients were infected by red blood cells from two HBV seroconverting donors before the introduction of HBV-nucleic acid testing. CONCLUSION: HIV, HCV and HBV incidence rates in blood donors declined over the two past decades in France. There is a very small risk of a blood component that tests negative entering the blood supply resulting in TT infections, especially after introduction of molecular assays in donor screening.

Hypersensitivity transfusion reactions to fresh frozen plasma: a retrospective analysis of the French hemovigilance network.

Few data are currently available on hypersensitivity transfusion reactions (HTRs) after exposure to fresh frozen plasma (FFP). Between 2000 and 2018, three different FFP production strategies have been used in France, leading to the concomitant use of different types of FFP. The objective of this study was to describe the rate of FFP-related HTRs and to assess the relative risk of each type of FFP. HTR following FFP transfusion between 2000 and 2018 were retrospectively extracted from the national hemovigilance database of the French National Agency for Medicines and Health Products Safety (ANSM). Temporal evolution of the incidence of reactions was modeled using logistic regression. During the study period, the overall rate of FFP-related HTRs was 52.0 (95% CI 50.2-53.9) reactions per 100,000 units of FFP issued. The rate of FFP-related HTRs progressively increased over the study period, from 28.7 (95% CI 22.8-36.0) in 2000 to 88.9 (78.8-100.3) reactions per 100,000 units of FFP issued in 2018 (OR 1.08 [1.07 - 1.09], P < .001), whereas the rate of other types of adverse transfusion reactions (ATRs) decreased. Between 2000 and 2014, its period of use, Solvent-Detergent-treated Apheresis FFP (SD-APH) was associated with the lowest risk of HTR. Our results indicate that although the rate of HTRs to FFP is low in France, the risk of having such a reaction has steadily increased between 2000 and 2018. A declarative bias is unlikely as the rate of other type of FFP-related ATRs decreased over the same period. The risk of HTRs to FFP is suggested to differ according to the processing of the FFP with a lower risk for SD-APH.

Pathogenic and likely pathogenic variants in at least five genes account for approximately 3% of mild isolated nonsyndromic thrombocytopenia.

BACKGROUND: Thrombocytopenia has a variety of different etiologies, both acquired and hereditary. Inherited thrombocytopenia may be associated with other symptoms (syndromic forms) or may be strictly isolated. To date, only about half of all the familial forms of thrombocytopenia have been accounted for in terms of well-defined genetic abnormalities. However, data are limited on the nature and frequency of the underlying causative genetic variants in individuals with mild isolated nonsyndromic thrombocytopenia. STUDY DESIGN AND METHODS: Thirteen known or candidate genes for isolated thrombocytopenia were included in a gene panel analysis in which targeted next-generation sequencing was performed on 448 French blood donors with mild isolated nonsyndromic thrombocytopenia. RESULTS: A total of 68 rare variants, including missense, splice site, frameshift, nonsense, and in-frame variants (all heterozygous) were identified in 11 of the 13 genes screened. Twenty-nine percent (N = 20) of the variants detected were absent from both the French Exome Project and gnomAD exome databases. Using stringent criteria and an unbiased approach, we classified seven predicted loss-of-function variants (three in ITGA2B and four in TUBB1) and four missense variants (one in GP1BA, two in ITGB3 and one in ACTN1) as being pathogenic or likely pathogenic. Altogether, they were found in 13 members (approx. 3%) of our studied cohort. CONCLUSION: We present the results of gene panel sequencing of known and candidate thrombocytopenia genes in mild isolated nonsyndromic thrombocytopenia. Pathogenic and likely pathogenic variants in five known thrombocytopenia genes were identified, accounting for approximately 3% of individuals with the condition.

Are single-donor red blood cell transfusions still relevant for preterm infants?

OBJECTIVE: To explore the worth of a single-donor program for preterm infants through the recipient profile and the impact on donor exposure, red blood cell (RBC) pack waste, storage duration, and transfusion performance. STUDY DESIGN: Patients and transfusion characteristics were collected for 3 years (2015-2017) in preterm infants according to single-donor program prescription in a unit not practicing placental transfusion or erythropoietin supplementation. RESULTS: Among 1048 eligible preterm infants, 161 met the inclusion criteria, and 51 received single-donor packs. Our single-donor program induced a donor number reduction (34% less than the transfusion number) and an extension of storage duration (median: 9 versus 7 days, p < 0.0001) without altering the transfusion performance. However, 41% of small packs were not used. CONCLUSION: A single-donor program partially reduced donor exposure but led to drastic RBC pack waste. Optimization of transfusion alternatives may increase this phenomenon, calling into question the rationale of this practice.

An essential role for α4A-tubulin in platelet biogenesis.

During platelet biogenesis, microtubules (MTs) are arranged into submembranous structures (the marginal band) that encircle the cell in a single plane. This unique MT array has no equivalent in any other mammalian cell, and the mechanisms responsible for this particular mode of assembly are not fully understood. One possibility is that platelet MTs are composed of a particular set of tubulin isotypes that carry specific posttranslational modifications. Although ß1-tubulin is known to be essential, no equivalent roles of α-tubulin isotypes in platelet formation or function have so far been reported. Here, we identify α4A-tubulin as a predominant α-tubulin isotype in platelets. Similar to ß1-tubulin, α4A-tubulin expression is up-regulated during the late stages of megakaryocyte differentiation. Missense mutations in the α4A-tubulin gene cause macrothrombocytopenia in mice and humans. Defects in α4A-tubulin lead to changes in tubulin tyrosination status of the platelet tubulin pool. Ultrastructural defects include reduced numbers and misarranged MT coils in the platelet marginal band. We further observed defects in megakaryocyte maturation and proplatelet formation in Tuba4a-mutant mice. We have, thus, discovered an α-tubulin isotype with specific and essential roles in platelet biogenesis.

Choosing Wisely, another way to spread blood transfusion's good practices.

Medical practice should be as much as possible ruled by evidence-based medicine. A lot of experts contribute to that, in heavy structured procedures where they write detailed and precise clinical practice recommendations. Such documents are essential but they are often far from everyday questions patients and their general practitioners are asking. There is room for a more concise and practical approach and that is "Choosing Wisely". This approach asks every medical society to identify "things physicians and patients should question" and provide clear and proven replies. In doing so, it is expected a reduction of overused exams, treatments, or procedures which are not helpful for patients. "Better treated with less" is the global idea. A lot of countries are now going down that road, including France who plans to develop it. Several of them have blood transfusion societies which have already published their recommendations, and also first studies on their impact on the ground. Comparison of these works shows clearly that priorities are nearly the same everywhere.

Acquired red blood cell alloantibodies in transfused patients of 80 years or over: a 2008-2013 national haemovigilance survey.

BACKGROUND: As transfusion in the elderly patients has increased over the last decades, and with the aim of improving blood policy, post-transfusion red blood cell alloimmunisation, a delayed serological transfusion reaction, was investigated in patients 80 years old or over. MATERIALS AND METHODS: For every adverse reaction to a transfusion, a report is sent to the French haemovigilance database. All cases of red blood cell alloimmunisation reported in the haemovigilance database were collected, and an analysis was performed on those cases in transfused patients 80 years old or over. RESULTS: There were 11,625 reports of red blood cell alloimmunisation from 1 January, 2008 to 31 December, 2013, of which 3,617 (31.1%) occurred in patients 80 years old or over. Among this subgroup, red blood cell concentrates were the most frequently involved blood component (3,482 reports, 96.3%). Red blood cell alloimmunisation after transfusion of platelet concentrates was also notified (132 reports, 3.7%). Anti-KEL1 was the most frequent antibody (874 reports, 24.2%). The imputability of the blood component was certain in 2,340 cases (64.7%) and probable in 1,078 (29.8%). In 2013, the incidence of red blood cell alloimmunisation was 4.14 per 1,000 transfused patients aged 80 years old or over. DISCUSSION: In a 6-year national survey in which 40,570 reports were made, there were 3,617 cases of red blood cell alloimmunisation in transfused recipients of 80 years old or over. This delayed serological transfusion reaction is not rare. Red blood cell concentrates were predominantly involved, but cases caused by platelet concentrates were also described. In order to prevent alloimmunisation in the elderly, several factors must be evaluated before transfusing matched red blood cell concentrates: the patient's age, pathology and its outcome, the type of transfusion support (chronic or not), life expectancy, and blood product availability.

[Evaluation of the professional practices of physicians in transfusion technology and medicine]. / L'évaluation des pratiques professionnelles des médecins en technologie et médecine transfusionnelles.

The evaluation of the professional practices (EPP) is obligatory for all the physicians since July 1, 2005 for a first five-year period. It represents one of the components of the continuous medical training (CMT). The French Society of Blood Transfusion and National Institute of Blood Transfusion are the promoters of the EPP in transfusion technology and medicine. Initially, the programs of EPP will be conceived and controlled by experts and will relate to their basic activities. During a five years cycle, the physician taking part in a program must validate a specific action and take part in a rolling programme. At the end of the programme, the physician will receive a certificate issued by National Institute of Blood Transfusion and will have to submit it to a committee placed under the responsibility of the regional physicians' committee.

[Future technological evolutions in blood donation qualification]. / Les évolutions technologiques dans la qualification biologique des dons de sang.

In the past decades, blood donation screening contributed significantly to blood safety improvement, thanks to the increasing performances of serological and nucleic acid testing (NAT) assays, as well as the evolution of automated systems technology. The rapid pace of NAT development can be clearly seen to extend into the future. NAT for additional viruses as well as the use of new automated systems for individual donation or smaller mini-pool testing, with multiplex assays, is currently debated. However, few added benefit is expected for blood safety from such developments, while cost-effectiveness appears to be poor. The next step in laboratory automation will probably be the implementation of robotic pre- and post-analytical procedures. In this article we review the potential future evolutions of screening technologies in blood qualification platforms, particularly those derived from nanobiotechnologies. DNA microarrays, Lab-On-Chips, biosensors and nanoparticles (quantum dots) will probably play a major role in the coming decade.