The effect of donation frequency on donor health in blood donors donating plasma by plasmapheresis: study protocol for a randomized controlled trial.

BACKGROUND: The demand for plasma products is growing, necessitating an increase in plasma collection by plasmapheresis. While the 20th edition of the European Guidelines permits plasma donors in Europe to donate with 96-h donation intervals, the potential short- and long-term consequences of high-frequency plasma donations on donor health remain unknown. This study aims to measure the effect of plasma donation frequency on plasma protein composition, including total serum protein (TSP) and immunoglobulin G (IgG), in Norwegian male blood donors. METHODS: This randomized controlled trial (RCT) included 120 male blood donors who were randomized into two intervention groups and one control group: high-frequency plasma donors (HFPDs) who donated 650 mL of plasma 3 times every 2 weeks, whereas regular-frequency plasma donors (RFPDs) who donated 650 mL of plasma 1 time every 2 weeks. The control group consisted of whole blood donors. The primary outcomes are the concentrations of TSP and IgG. DISCUSSION: The findings from this study may have implications for recommendations related to donor health and plasma donation frequencies and may contribute to supporting the strategic independence of plasma products in Norway and Europe without compromising donor health. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05179200 . Registered December 20th, 2021.

Convalescent plasma from Norwegian blood donors to treat COVID-19. / Rekonvalesensplasma mot covid-19 fremstilt fra norske blodgivere.

BACKGROUND: At the start of the pandemic, the Norwegian Directorate of Health and Norwegian blood banks initiated the production of COVID-19 convalescent plasma within the framework of clinical studies. In this article we describe the blood donors who participated. MATERIAL AND METHOD: Blood donors who had recovered from COVID-19 were recruited to donate single donor plasma for the purpose of patient treatment. Data on the course of infection, leukocyte antibodies and antibody level against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) per plasma unit were registered after informed consent was obtained. We calculated a disease score defined as the total number of self-reported symptoms/findings and hospitalisation where relevant (score 0-⁠11). RESULTS: A total of 1644 plasma units were collected from 266 plasma donors at 12 blood banks. Median disease score was 5 (interquartile range 3-⁠6), and 15 donors had recovered from pneumonia and/or been hospitalised. A total of 599/1644 plasma units from 106/266 donors met our requirement for SARS-CoV-2 antibody content (> 60 % inhibition of virus binding to angiotensin-converting enzyme 2 (ACE2)) or positive virus neutralisation test. The antibody level in donors waned over time following infection, and showed no clear correlation with disease score. INTERPRETATION: The number of symptoms and findings in blood donors could not predict antibody response at individual level, and antibody testing was crucial for the production of effective convalescent plasma.

Plasma collection and supply in Europe: Proceedings of an International Plasma and Fractionation Association and European Blood Alliance symposium.

At the symposium organized by the International Plasma and Fractionation Association and European Blood Alliance, experts presented their views and experiences showing that the public sector and its blood establishments may strengthen the collection and increase the supply of plasma using the right strategies in plasma donor recruitment, retention and protection, scaling-up collection by increasing the number of donors within improved/new infrastructure, supportive funding, policies and legislation as well as harmonization of clinical guidelines and the collaboration of all stakeholders. Such approaches should contribute to increased plasma collection in Europe to meet patients' needs for plasma-derived medicinal products, notably immunoglobulins and avoid shortages. Overall, presentations and discussions confirmed that European non-profit transfusion institutions are committed to increasing the collection of plasma for fractionation from unpaid donors through dedicated programmes as well as novel strategies and research.

Safe Blood Donation from Donors Using Antihypertensive Medication. A Multi-Center Retrospective Quality Study from South-East Norway.

Purpose: In Norway, blood donors using antihypertensive medication were deferred until 2015. Following revision of the national directive, these donors could be allowed, providing stable dose for at least 3 months, adequate blood pressure control and no adverse effects caused by the therapy. The new practice was evaluated by a quality study where the major aim was to establish whether donations from blood donors on antihypertensive medication pose a risk to the donor. The risk was assessed by counting the number and categorizing the adverse events related to blood donation. In addition, the quantitative effect of including these donors was calculated. Subjects and Methods: In this retrospective quality study, blood donors on antihypertensive therapy were recruited from four different blood centers to fill out a questionnaire. A total of 265 donors answered questions regarding their health status, type of medication used, and adverse events connected to blood donation both before and after starting the therapy. Results: No severe adverse events were observed in donors on antihypertensive medications. The amount of mild adverse events, as exhibited by only 7 persons (0.46%) in this donor population, was the same as for donors without hypertensive treatment. Conclusion: Blood donation from persons on antihypertensive therapy poses no extra risk of severe adverse events, given the use of screening criteria to identify and bleed only low-risk donors.

Correction to: Diagnosis and Treatment of Genetic HFE-Hemochromatosis: The Danish Aspect.

[This corrects the article DOI: 10.14740/gr1206.].

A novel hepcidin mutation.

BACKGROUND: The bioactive peptide hormone hepcidin-25 regulates iron levels by inhibiting iron transport to plasma via ferroportin. Hepcidin-25 is synthesized in the liver where the 84 amino acids pro-hepcidin is cleaved into the bioactive hepcidin-25. A patient admitted to the hospital presented with infertility and fatigue. METHODS: Genomic DNA was purified from whole blood using the Maxwell 16 system (Promega). MLPA analysis was performed to detect large genomic rearrangements using the SALSA MLPA kit # P347, Hemochromatosis (MRC Holland, Holland). Plasma hepcidin measurements were performed using liquid chromatography/tandem mass spectrometry (LC-MS/MS). RESULTS: A novel HAMP mutation (homozygous one base deletion in c.215delG, p.Cys72Serfs*?) was detected. The deletion in nucleotide 215 causes a frameshift altering the predicted protein sequence from cysteine13 in mature peptide. Whether this leads to nonsense mediated decay of the mRNA or synthesis of an aberrant peptide in unknown, but bioactive hepcidin-25 was undetectable in plasma. The patient had massive iron overload with ferritin up to 8360 µg/L. He was anaemic with a Hb at 7.0 mmol/L (11.3 g/dL) and suffered from hypogonadotropic hypogonadism with a total testosterone of 1.2 nmol/l. Continued treatment with venesection and gonadotropins led to reduced fatigue, reduction in iron overload, a normalized Hb and improvement of semen quality. CONCLUSION: A novel hepcidin mutation was detected in a patient with massive iron overload, fatigue and hypogonadotropic hypogonadism.

Variations in hemoglobin measurement and eligibility criteria across blood donation services are associated with differing low-hemoglobin deferral rates: a BEST Collaborative study.

BACKGROUND: Determination of blood donor hemoglobin (Hb) levels is a pre-requisite to ensure donor safety and blood product quality. We aimed to identify Hb measurement practices across blood donation services and to what extent differences associate with low-Hb deferral rates. METHODS: An online survey was performed among Biomedical Excellence for Safer Transfusion (BEST) Collaborative members, extended with published data. Multivariable negative-binomial regression models were built to estimate adjusted associations of minimum donation intervals, Hb cut-offs (high, ≥13.5 g/dL in men or ≥ 12.5 g/dL in women, vs. lower values), iron monitoring (yes/no), providing or prescribing iron supplementation (yes/no), post-versus pre-donation Hb measurement and geographical location (Asian vs. rest), with low-Hb deferral rates. RESULTS: Data were included from 38 blood services. Low-Hb deferral rates varied from 0.11% to 8.81% among men and 0.84% to 31.85% among women. Services with longer minimum donation intervals had significantly lower deferral rates among both women (rate ratio, RR 0.53, 95%CI 0.33-0.84) and men (RR 0.53, 95%CI 0.31-0.90). In women, iron supplementation was associated with lower Hb deferral rates (RR 0.47, 95%CI 0.23-0.94). Finally, being located in Asia was associated with higher low-Hb deferral rates; RR 9.10 (95%CI 3.89-21.27) for women and 6.76 (95%CI 2.45-18.68) for men. CONCLUSION: Differences in Hb measurement and eligibility criteria, particularly longer donation intervals and iron supplementation in women, are associated with variations in low-Hb deferral rates. These insights could help improve both blood donation service efficiency and donor care.

Diagnosis and Treatment of Genetic HFE-Hemochromatosis: The Danish Aspect.

This paper outlines the Danish aspects of HFE-hemochromatosis, which is the most frequent genetic predisposition to iron overload in the five million ethnic Danes; more than 20,000 people are homozygous for the C282Y mutation and more than 500,000 people are compound heterozygous or heterozygous for the HFE-mutations. The disorder has a long preclinical stage with gradually increasing body iron overload and eventually 30% of men will develop clinically overt disease, presenting with symptoms of fatigue, arthralgias, reduced libido, erectile dysfunction, cardiac disease and diabetes. Subsequently the disease may progress into irreversible arthritis, liver cirrhosis, cardiomyopathy, pancreatic fibrosis and osteoporosis. The effective standard treatment is repeated phlebotomies, which in the preclinical and early clinical stages ensures a normal survival rate. Early detection of the genetic predisposition to the disorder is therefore important to reduce the overall burden of clinical disease. Population screening seems to be cost-effective and should be considered.

[Genetic HFE-haemochromatosis].

HFE-haemochromatosis is the most frequent genetic disposition for iron overload in ethnic Danes: 20,000 persons are homozygous for the C282Y mutation. The disorder has a long preclinical phase with increasing body iron overload, and 30% of males will develop clinically overt disease, presenting with symptoms of fatigue, arthralgias, reduced libido, erectile dysfunction, cardiac disease, diabetes and liver disease, later progressing into cirrhosis, cardio-myo-pathy, pancreatic fibrosis and osteoporosis. Treatment consists of phlebotomies, which in the preclinical and early clinical phases ensure normal survival.

Temporary impact of blood donation on physical performance and hematologic variables in women.

BACKGROUND: No former studies have examined how blood donation influences physical performance in women, who due to menstruation may have a slower recovery of performance. Therefore, the aim of this study was to clarify how VO2peak , time trial (TT) performance, and hematologic variables are affected in 18 iron-sufficient (plasma ferritin [P-ferritin] > 30 µg/L) women after a standard 450-mL blood donation. STUDY DESIGN AND METHODS: VO2peak , TT performance, and blood variables were measured at baseline and 3, 7, 14, 21, and 28 days after blood donation in 18 iron-sufficient women. Anthropometrics were measured at baseline and Day 28. RESULTS: VO2peak was reduced by 7.5 ± 1.1% from 2973 ± 87 mL/min at baseline to 2765 ± 73 mL/min 3 days after blood donation and remained below baseline until 28 days. The TT performance was reduced by 5.2 ± 1.0% from baseline (868 ± 31 sec) to Day 3 (915 ± 29 sec), but was not different from baseline 14 days after blood donation. Blood hemoglobin (B-Hb) concentration declined by 7.6 ± 2.1% from 8.4 ± 0.1 to 7.8 ± 0.1 mmol/L at baseline and on Day 3, respectively. P-ferritin at baseline was 58 ± 7 µg/L and it decreased (55 ± 3%) to a nadir of 24 ± 3 µg/L 28 days after blood donation and remained lower at 36 ± 4 µg/L after 90 days. CONCLUSION: VO2peak and B-Hb were only recovered 28 days after a blood donation whereas TT performance was back to baseline 14 days after blood donation.

Handling low hemoglobin and iron deficiency in a blood donor population: 2 years' experience.

BACKGROUND: Iron deficiency and blood donors with low hemoglobin (Hb) concentration are well-known challenges in any blood bank setting. In the Capital Region of Denmark, a new approach was adopted that centralized measurement of Hb, initiated ferritin (F) measurement, and established a center for donor Hb and iron. An algorithm was created based on Hb and F levels, which drove decisions on outreach by the donor Hb and iron resource team to the donor, including whether to provide iron supplementation or, on rare occasions, a referral to the donor's general practitioner. STUDY DESIGN AND METHODS: The change in Hb for repeat donors was followed during the first 2 years of the intervention strategy, which included measurements of F and offering intermittent iron supplementation to some of the donors. RESULTS: In 2 years, 62,663 blood donors donated 193,288 units of blood and 318 donors gave 754 complete blood count blood samples. Over time in the repeat donors, the Hb increased from 15.39 to 15.60 g/dL and 13.85 to 14.06 g/dL in male and female donors, respectively, and the proportion of donors with low Hb decreased from 0.9% to 0.3% and 3.9% to 2.7% for the male and female donors, respectively. CONCLUSION: The program with goal-directed iron supplementation only to those that would benefit has led to an increase in Hb concentration and a reduction in the proportion of donors with low Hb concentration.

Viable bacteria associated with red blood cells and plasma in freshly drawn blood donations.

OBJECTIVES: Infection remains a leading cause of post-transfusion mortality and morbidity. Bacterial contamination is, however, detected in less than 0.1% of blood units tested. The aim of the study was to identify viable bacteria in standard blood-pack units, with particular focus on bacteria from the oral cavity, and to determine the distribution of bacteria revealed in plasma and in the red blood cell (RBC)-fraction. DESIGN: Cross-sectional study. Blood were separated into plasma and RBC-suspensions, which were incubated anaerobically or aerobically for 7 days on trypticase soy blood agar (TSA) or blue lactose plates. For identification colony PCR was performed using primers targeting 16S rDNA. SETTING: Blood donors attending Capital Region Blood Bank, Copenhagen University Hospital, Rigshospitalet, Hvidovre, Denmark, October 29th to December 10th 2013. PARTICIPANTS: 60 donors (≥50 years old), self-reported medically healthy. RESULTS: Bacterial growth was observed on plates inoculated with plasma or RBCs from 62% of the blood donations. Growth was evident in 21 (35%) of 60 RBC-fractions and in 32 (53%) of 60 plasma-fractions versus 8 of 60 negative controls (p = 0.005 and p = 2.6x10-6, respectively). Propionibacterium acnes was found in 23% of the donations, and Staphylococcus epidermidis in 38%. The majority of bacteria identified in the present study were either facultative anaerobic (59.5%) or anaerobic (27.8%) species, which are not likely to be detected during current routine screening. CONCLUSIONS: Viable bacteria are present in blood from donors self-reported as medically healthy, indicating that conventional test systems employed by blood banks insufficiently detect bacteria in plasma. Further investigation is needed to determine whether routine testing for anaerobic bacteria and testing of RBC-fractions for adherent bacteria should be recommended.

Time course for the recovery of physical performance, blood hemoglobin, and ferritin content after blood donation.

BACKGROUND: It is widely accepted that blood donation negatively affects endurance performance, but data on physical recovery after a standard blood donation are scarce. This study aimed to elucidate the temporary impact of blood donation on endurance performance, measured as peak oxygen uptake (VO2peak ) and time trial (TT) performance. STUDY DESIGN AND METHODS: VO2peak , TT performance, blood, iron, and anthropometric variables were determined before (baseline) and 3, 7, 14, and 28 days after blood donation in 19 healthy men. RESULTS: VO2peak was reduced by 6.5% from 49.7 ± 2 mL/kg/min at baseline to 46.3 ± 2 mL/kg/min on Day 3 (p < 0.001), and TT performance was reduced by 5.2% from 13:31 ± 00:42 to 14:13 ± 00:50 min:sec (p < 0.001). Both VO2peak and TT performance were back to baseline 14 days after blood donation. Blood hemoglobin (Hb) concentration declined 7.9% from 9.3 ± 0.11 mmol/L at baseline to 8.6 ± 0.1 mmol/L on Day 3 (p < 0.001) and was not different from baseline 28 days after blood donation. The hematocrit (Hct) was reduced from 43.8 ± 0.5% at baseline to 40.6 ± 0.6% on Day 3 (p < 0.001). On Day 28 Hct was 42.8 ± 0.5% and still reduced below baseline (p = 0.028). Ferritin concentration was reduced 46% from 113 ± 23 µg/L at baseline to a minimum of 61 ± 14 µg/L on Day 14 (p = 0.008). CONCLUSION: The individual recovery was variable, but physical performance was recovered 14 days after a standard blood donation, despite blood Hb concentration remaining lower than at baseline.

Predictors of iron levels in 14,737 Danish blood donors: results from the Danish Blood Donor Study.

BACKGROUND: Dietary studies show a relationship between the intake of iron enhancers and inhibitors and iron stores in the general population. However, the impact of dietary factors on the iron stores of blood donors, whose iron status is affected by blood donations, is incompletely understood. STUDY DESIGN AND METHODS: In the Danish Blood Donor Study, we assessed the effect of blood donation frequency, physiologic factors, lifestyle and supplemental factors, and dietary factors on ferritin levels. We used multiple linear and logistic regression analyses stratified by sex and menopausal status. RESULTS: Among high-frequency donors (more than nine donations in the past 3 years), we found iron deficiency (ferritin below 15 ng/mL) in 9, 39, and 22% of men, premenopausal women, and postmenopausal women, respectively. The strongest predictors of iron deficiency were sex, menopausal status, the number of blood donations in a 3-year period, and the time since last donation. Other significant factors included weight, age, intensity of menstruation, iron tablets, vitamin pills, and consumption of meat and wine. CONCLUSION: The study confirms iron deficiency as an important problem, especially among menstruating women donating frequently. The risk of iron depletion was largely explained by sex, menopausal status, and donation frequency. Other factors, including dietary and supplemental iron intake, had a much weaker effect on the risk of iron depletion.

A genetic risk factor for low serum ferritin levels in Danish blood donors.

BACKGROUND: Iron deficiency is a frequent side effect of blood donation. In recent years, several studies have described genetic variants associated with iron concentrations. However, the impact of these variants on iron levels is unknown in blood donors. Knowledge of genetic variants that predispose donors to iron deficiency would allow bleeding frequency and iron supplementation to be tailored to the individual donor. STUDY DESIGN AND METHODS: The genotypes of five specific single-nucleotide polymorphisms (SNPs) in three genes that have been previously associated with iron status and/or restless leg syndrome (RLS) were investigated in two groups of female blood donors. The first group had low iron stores (serum ferritin ≤ 12 µg/L, n = 657), and the second group had normal to high iron stores (serum ferritin > 30 µg/L, n = 645). Genotype distribution for each of the SNPs was compared between the two groups. RESULTS: Homozygosity for the T-allele of BTBD9 rs9296249 was associated with lower serum ferritin. The odds ratio for low serum ferritin was 1.35 (95% confidence interval, 1.02-1.77; p = 0.03) when comparing donors with the TT genotype with donors with the CT genotype. CONCLUSION: A frequent polymorphism in BTBD9 was significantly associated with serum ferritin. This polymorphism has previously been associated with RLS, but not low iron stores in blood donors.

Storage-induced increase in biomarkers of oxidative stress and inflammation in red blood cell components.

BACKGROUND: Transfusion of blood components may increase the risk of complications in relation to surgery. During storage, red blood cells (RBCs) undergo structural and functional changes that may reduce function and viability after transfusion. The aim of the study was to evaluate the quality of buffy-coat reduced red cells in SAG-M additive solution, by assessing biomarkers of oxidative and inflammatory stress during a storage period of 35 days. STUDY DESIGN AND METHODS: Ten units of RBCs were stored for 35 days. Samples were collected from the units at storage days 1, 3, 7, 14, 21, 28 and 35, respectively. The samples were analysed for various biomarkers expressing the oxidative stress and inflammation, including malondialdehyde (MDA), α-tocopherol (AT), dehydroascorbic acid (DHA), ascorbate (ASC), YKL-40 and interleukin-6 (IL-6). RESULTS: The levels ofMDA, ASC, DHA, IL-6 and YKL-40 changed significantly during the storage period (p < 0.001, p < 0.001, p < 0.001, p = 0.004 and p < 0.001 respectively). A significant change in AT levels could not be shown (p = 0.087). CONCLUSIONS: RBCs displayed significant changes in all measured indices of oxidative and inflammatory stress during a storage period of 35 days except for AT. The data suggest a possible rationale behind the observation that aging blood products may increase the risk of complications following surgery and blood transfusion.

The effect of a standardized protocol for iron supplementation to blood donors low in hemoglobin concentration.

BACKGROUND: Iron deficiency leading to low hemoglobin concentration (cHb) is a common problem for blood donors as well as for blood banks. A standardized protocol offering iron supplementation based on P-ferritin determination may help to reduce the problem and retain donors. STUDY DESIGN AND METHODS: This was a prospective study where 879 blood donors, presenting with cHb at or below the limit of acceptance for donation, were included. The predonation cHb result was read after donation. The donors received 50 iron tablets (JernC or Ferrochel, 100 or 25 mg elemental iron, respectively), and samples for P-ferritin, mean corpuscular volume, and control of cHb were secured. Based on a P-ferritin level of less than 60 microg per L, 20 iron tablets were offered after all following donations. RESULTS: Mean cHb was 7.6 mmol per L (122 g/L) and 8.2 mmol per L (132 g/L) in women and men, respectively. In 80 percent of the women and 48 percent of the men, iron stores were low (P-ferritin < or = 30 microg/L). In the donors returning once or twice, an increase in cHb and P-ferritin was seen. Fifteen donors were permanently deferred due to disease and 36 due to low cHb, but 2 years after the start of the study, 79 percent of the women and 85 percent of the men were still active donors. CONCLUSION: A standardized protocol offering iron supplementation and simple oral and written advice based on P-ferritin measurements is effective in normalizing cHb and retaining donors presenting with cHb at or below the limit of acceptance for donation.