How to increase first-time donors' returns? The postdonation letter's content can make a difference.

BACKGROUND: Retention of first-time donors is pivotal for blood collection centers. The present study built on research showing the importance of donor identity among regular donors and sought to compare the effectiveness of various communication strategies on return rate. STUDY DESIGN AND METHODS: Postal letters were sent to a large sample of first-time whole blood donors (N = 1219) a few weeks following their first donation. Four versions of this letter were differently constructed in a way to boost the acquisition of donor identity (i.e., by including information about their ABO and Rh(D) blood group, emphasizing the salience of donor identity, offering a keyring with personalized information, or specifying the percentage of those sharing the same ABO and Rh(D) blood group). One version with no identity-related information served as a control condition. Participants' subsequent blood donations were tracked for 5-22 months after receiving the letter. RESULTS: Survival analysis showed that the return rate was significantly higher among those who had received information about the percentage of the country's population with the same ABO and Rh(D) blood group (in comparison with the four other versions). There was no significant effect on the blood type rarity. CONCLUSION: Blood collection centers could orient the strategy employed to communicate with first-time donors to improve donors' retention. Arousing a sense of social identification with others with the same blood type may reveal a promising avenue.

Transition to 37°C reveals importance of NADPH in mitigating oxidative stress in stored RBCs.

The RBC storage lesion is a multiparametric response that occurs during storage at 4°C, but its impact on transfused patients remains unclear. In studies of the RBC storage lesion, the temperature transition from cold storage to normal body temperature that occurs during transfusion has received limited attention. We hypothesized that multiple deleterious events might occur in this period of increasing temperature. We show dramatic alterations in several properties of therapeutic blood units stored at 4°C after warming them to normal body temperature (37°C), as well as febrile temperature (40°C). In particular, the intracellular content and redox state of NADP(H) were directly affected by post-storage incubation at 37°C, as well as by pro-oxidant storage conditions. Modulation of the NADPH-producing pentose phosphate pathway, but not the prevention of hemoglobin autoxidation by conversion of oxyhemoglobin to carboxyhemoglobin, provided protection against storage-induced alterations in RBCs, demonstrating the central role of NADPH in mitigating increased susceptibility of stored RBCs to oxidative stress. We propose that assessing RBC oxidative status after restoration of body temperature constitutes a sensitive method for detecting storage-related alterations that has the potential to improve the quality of stored RBCs for transfusion.

Current hepatitis E virus seroprevalence in Swiss blood donors and apparent decline from 1997 to 2016.

Background and aimHepatitis E virus (HEV) is a virus of emerging importance to transfusion medicine. Studies from several European countries, including Switzerland, have reported high seroprevalence of hepatitis E as a consequence of endemic infections. Published HEV seroprevalence estimates within developed countries vary considerably; primarily due to improved diagnostic assays. The purpose of this study was to investigate the seroprevalence of anti-HEV IgG in Swiss blood donations. Methods: We used the highly sensitive Wantai HEV IgG EIA and assessed regional distribution patterns. We analysed age- and sex-matched archive plasma dating back 20 years from canton Bern to investigate recent changes in HEV seroprevalence levels. Results: On average, 20.4% (95% confidence intervals: 19.1-21.8) of the 3,609 blood samples collected in 2014-16 were anti-HEV IgG positive; however, distinct differences between geographical regions were observed (range: 12.8-33.6%). Seroprevalence increased with age with 30.7% of males and 34.3% of women being positive donors over > 60 years old. Differences between sexes may be attributed to dissimilarities in the average age of this group. Within the specified region of the Bern canton, overall prevalence has declined over two decades from 30.3% in 1997/98 to 27.0% in 2006 and 22.3% in 2015/6. Conclusions: HEV seroprevalence in Switzerland is high, but has declined over the last decades. The result shows that primarily endemic HEV infections occur and that current blood products may pose a risk to vulnerable transfusion recipients. Nucleic acid screening of all blood products for HEV will begin in November 2018.

Factors associated with immune hemolytic anemia after pediatric liver transplantation.

Immune-mediated hemolytic anemia following SOT is a rare disorder, the risk factors for which are unknown. Our purpose was to analyze a seemingly increased incidence in our center with the aim to identify predisposing factors. This recipients single-center retrospective study reviewed the medical records of 96 pediatric LT between 2000 and 2013. IHA was defined as acute anemia with a positive direct antiglobulin test. Seven cases of immune-mediated hemolytic anemia were identified (incidence 8.5%). Three cases presented during the first 3 months following LT (early IHA), and 4 presented later (late IHA). All patients with late IHA required rituximab. Using univariate analysis, the following factors were associated with IHA onset: BA (P = .04), younger age (P = .04), and the use of IGL-1 preservation solution (P = .05). Late IHA was associated with viral infections occurring beyond 3 months following LT, younger age, and BA (P = .01). Overall, CMV infection was associated with the development of both early and late IHA: CMV-negative recipients who received an organ from a CMV-positive donor were more likely to develop IHA (P = .035), and de novo CMV infection during the first year post-LT was associated with late IHA (P = .03). IHA is a rare complication following pediatric LT, occurring more frequently in younger patients and patients with an initial diagnosis of BA. CMV-negative recipients and patients who experience a de novo CMV infection in the first year following LT seem particularly vulnerable. IGL-1 preservation solution may be associated with an increased likelihood of developing IHA, a novel finding which warrants further investigation.

Modulation of T-bet and Eomes during Maturation of Peripheral Blood NK Cells Does Not Depend on Licensing/Educating KIR.

Peripheral natural killer (NK) cells upregulate T-bet and downregulate Eomes, the key transcription factors regulating NK cell maturation and function during the last maturation steps toward terminally differentiated effector cells. During this process, NK cells acquire killer immunoglobulin-like receptors (KIR) and effector functions, such as cytotoxicity and target cell-induced cytokine production. Inhibitory KIR are pivotal in the control of effector functions, but whether they also modulate T-bet/Eomes expression is unknown. We have measured T-bet/Eomes levels, KIR expression, and effector functions of maturing CD94(neg)CD56(dim)NK cells using CD57 as surface marker for maturation. Our cohort consisted of 23 healthy blood donors (HBD) homozygous for the KIR A haplotype that contains only inhibitory KIR2DL1 (ligand HLA-C2), KIR2DL3 (ligand HLA-C1), and KIR3DL1 (ligand HLA-Bw4). We confirm that during maturation of NK cells, the number of KIR increases, levels of T-bet/Eomes are modulated, and that cells acquire effector functions, such as cytotoxicity (CD107) and target cell-induced cytokine production (TNF-α). Because maturation was associated with the increase of the number of KIR as well as with the modulation of T-bet/Eomes, the number of KIR correlated with the extent of T-bet/Eomes modulation. However, whether the KIR were triggered by their cognate HLA ligands or not had no impact on T-bet and Eomes expression, indicating that modulation of T-box transcription factors during NK cell maturation does not depend on signals conveyed by KIR. We discuss the relevance of this finding in the context of models of NK cell maturation while cautioning that results obtained in a perhaps quite heterogeneous cohort of HBD are not necessarily conclusive.

Long-lasting stem cell-like memory CD8+ T cells with a naïve-like profile upon yellow fever vaccination.

Efficient and persisting immune memory is essential for long-term protection from infectious and malignant diseases. The yellow fever (YF) vaccine is a live attenuated virus that mediates lifelong protection, with recent studies showing that the CD8(+) T cell response is particularly robust. Yet, limited data exist regarding the long-term CD8(+) T cell response, with no studies beyond 5 years after vaccination. We investigated 41 vaccinees, spanning 0.27 to 35 years after vaccination. YF-specific CD8(+) T cells were readily detected in almost all donors (38 of 41), with frequencies decreasing with time. As previously described, effector cells dominated the response early after vaccination. We detected a population of naïve-like YF-specific CD8(+) T cells that was stably maintained for more than 25 years and was capable of self-renewal ex vivo. In-depth analyses of markers and genome-wide mRNA profiling showed that naïve-like YF-specific CD8(+) T cells in vaccinees (i) were distinct from genuine naïve cells in unvaccinated donors, (ii) resembled the recently described stem cell-like memory subset (Tscm), and (iii) among all differentiated subsets, had profiles closest to naïve cells. Our findings reveal that CD8(+) Tscm are efficiently induced by a vaccine in humans, persist for decades, and preserve a naïveness-like profile. These data support YF vaccination as an optimal mechanistic model for the study of long-lasting memory CD8(+) T cells in humans.

Family study of a Swiss patient uncovered a novel genetic basis for the S-s-U+(var) phenotype.

BACKGROUND: The rare S-s- phenotype is typically found in persons of African origin. Three genetic bases underlying this phenotype have been identified so far: a large deletion including the GYPB gene, which encodes the S and s antigens, and two mutations affecting GYPB splicing (commonly called "P2" and "NY"). The discovery of the S-s- phenotype in a Swiss patient prompted this study. STUDY DESIGN AND METHODS: The GYPB genotype of the patient was analyzed with Beadchip technology and Sanger sequencing. GYPB haplotype analysis was also carried out in the patient's family. A functional splicing assay was developed to determine the impact of the identified mutation on GYPB splicing. RESULTS: Sanger sequencing of GYPB in the patient indicated that she was homozygous for a GYPB*s allele carrying a novel mutation in the splice donor site of Intron 5 (c.270+5G>A). Analysis of GYPB haplotypes in the patient's family revealed that she actually inherited this mutated GYPB*s allele from her mother of Swiss ancestry and a deleted GYPB allele from her father of Egyptian ancestry. Using a minigene-based splicing assay, we showed that GYPB mutation c.270+5G>A causes the skipping of Exon B5, as previously reported for the P2 mutation (c.270+5G>T). Consistently, the patient's red blood cells were found to be S-s-U+(var) . CONCLUSION: A novel GYPB mutation (c.270+5G>A) accounting for the S-s-U+(var) phenotype was identified. In contrast with P2 and NY mutations, which also drive this rare phenotype, this novel GYPB mutation inactivates a GYPB*s allele and does not appear to be of African origin.

Validation of hepcidin quantification in plasma using LC-HRMS and discovery of a new hepcidin isoform.

BACKGROUND: Hepcidin, a 25 amino acid peptide, plays an important role in iron homeostasis. Some hepcidin truncated peptides have antibiotic effects. RESULTS: A new analytical method for hepcidin determination in human plasma using LC-HRMS operating in full-scan acquisition mode has been validated. The extraction consists of protein precipitation and a drying reconstitution step; a 2.1 x 50 mm (idxL) C18 analytical column was used. Detection specificity, stability, accuracy, precision and recoveries were determined. The LOQ/LOD were 0.25/0.1 nM, respectively. More than 600 injections of plasma extracts were performed, allowing evaluation of the assay robustness. Hepcidin-20, hepcidin-22 and a new isoform, hepcidin-24, were detected in patients. CONCLUSION: The data underscore the usefulness of LC-HRMS for in-depth investigations related to hepcidin levels and pathways.

Effect of iron supplementation on fatigue in nonanemic menstruating women with low ferritin: a randomized controlled trial.

BACKGROUND: The true benefit of iron supplementation for nonanemic menstruating women with fatigue is unknown. We studied the effect of oral iron therapy on fatigue and quality of life, as well as on hemoglobin, ferritin and soluble transferrin receptor levels, in nonanemic iron-deficient women with unexplained fatigue. METHODS: We performed a multicentre, parallel, randomized controlled, closed-label, observer-blinded trial. We recruited from the practices of 44 primary care physicians in France from March to July 2006. We randomly assigned 198 women aged 18-53 years who complained of fatigue and who had a ferritin level of less than 50 ug/L and hemoglobin greater than 12.0 g/dL to receive either oral ferrous sulfate (80 mg of elemental iron daily; n=102) or placebo (n=96) for 12 weeks. The primary outcome was fatigue as measured on the Current and Past Psychological Scale. Biological markers were measured at 6 and 12 weeks. RESULTS: The mean score on the Current and Past Psychological Scale for fatigue decreased by 47.7% in the iron group and by 28.8% in the placebo group (difference -18.9%, 95% CI -34.5 to -3.2; p=0.02), but there were no significant effects on quality of life (p=0.2), depression (p=0.97) or anxiety (p=0.5). Compared with placebo, iron supplementation increased hemoglobin (0.32 g/dL; p=0.002) and ferritin (11.4 µg/L; p<0.001) and decreased soluble transferrin receptor (-0.54 mg/L; p<0.001) at 12 weeks. INTERPRETATION: Iron supplementation should be considered for women with unexplained fatigue who have ferritin levels below 50 µg/L. We suggest assessing the efficiency using blood markers after six weeks of treatment. Trial registration no. EudraCT 2006-000478-56.

Clinical evaluation of iron treatment efficiency among non-anemic but iron-deficient female blood donors: a randomized controlled trial.

BACKGROUND: Iron deficiency without anemia is related to adverse symptoms that can be relieved by supplementation. Since a blood donation can induce such an iron deficiency, we investigated the clinical impact of iron treatment after a blood donation. METHODS: One week after donation, we randomly assigned 154 female donors with iron deficiency without anemia, aged below 50 years, to a four-week oral treatment of ferrous sulfate versus a placebo. The main outcome was the change in the level of fatigue before and after the intervention. Aerobic capacity, mood disorder, quality of life, compliance and adverse events were also evaluated. Hemoglobin and ferritin were used as biological markers. RESULTS: The effect of the treatment from baseline to four weeks of iron treatment was an increase in hemoglobin and ferritin levels to 5.2 g/L (P < 0.01) and 14.8 ng/mL (P < 0.01), respectively. No significant clinical effect was observed for fatigue (-0.15 points, 95% confidence interval -0.9 points to 0.6 points, P = 0.697) or for other outcomes. Compliance and interruption for side effects was similar in both groups. Additionally, blood donation did not induce overt symptoms of fatigue in spite of the significant biological changes it produces. CONCLUSIONS: These data are valuable as they enable us to conclude that donors with iron deficiency without anemia after a blood donation would not clinically benefit from iron supplementation. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00981877.

The impact of iron supplementation efficiency in female blood donors with a decreased ferritin level and no anaemia. Rationale and design of a randomised controlled trial: a study protocol.

BACKGROUND: There is no recommendation to screen ferritin level in blood donors, even though several studies have noted the high prevalence of iron deficiency after blood donation, particularly among menstruating females. Furthermore, some clinical trials have shown that non-anaemic women with unexplained fatigue may benefit from iron supplementation. Our objective is to determine the clinical effect of iron supplementation on fatigue in female blood donors without anaemia, but with a mean serum ferritin < or = 30 ng/ml. METHODS/DESIGN: In a double blind randomised controlled trial, we will measure blood count and ferritin level of women under age 50 yr, who donate blood to the University Hospital of Lausanne Blood Transfusion Department, at the time of the donation and after 1 week. One hundred and forty donors with a ferritin level < or = 30 ng/ml and haemoglobin level >/= 120 g/l (non-anaemic) a week after the donation will be included in the study and randomised. A one-month course of oral ferrous sulphate (80 mg/day of elemental iron) will be introduced vs. placebo. Self-reported fatigue will be measured using a visual analogue scale. Secondary outcomes are: score of fatigue (Fatigue Severity Scale), maximal aerobic power (Chester Step Test), quality of life (SF-12), and mood disorders (Prime-MD). Haemoglobin and ferritin concentration will be monitored before and after the intervention. DISCUSSION: Iron deficiency is a potential problem for all blood donors, especially menstruating women. To our knowledge, no other intervention study has yet evaluated the impact of iron supplementation on subjective symptoms after a blood donation. TRIAL REGISTRATION: NCT00689793.

Breakthrough invasive pulmonary aspergillosis despite empirical voriconazole therapy for febrile neutropenia: case report and review of the literature.

We report the development of invasive pulmonary aspergillosis in a patient treated for acute myeloid leukaemia during empirical voriconazole therapy for febrile neutropenia. The patient failed to respond to the institution of salvage combination therapy with amphotericin B and voriconazole, but survived after adjunctive surgical resection.