Interdonation Interval Research Articles

Two‐year follow‐up of donors in a large national study of ferritin testing

We assessed donor return rates, donation frequency, and factors related to the evolution of ferritin levels 2 years after entering donors into a large operational study of ferritin testing. Ferritin testing was done on donors from representative clinics (n = 12,595). Low-ferritin donors (<25 μg/L) were informed and not called for 6 months to book a donation. Approximately 37% of donors had ferritin retested on a return donation. Return rate and donation frequency were monitored, and a logistic regression model was constructed. The return rate was lower in low-ferritin donors (67% vs. 78%), particularly in women who were first-time donors (36% vs. 61%). Returning low-ferritin donors made fewer donations in the 2 years after notification compared to the 2 years prenotification (4.5 vs. 7.5 for men, 3.0 vs. 5.0 for women), while donation frequency was lower and increased slightly for normal-ferritin donors (4.7 vs. 4.4 for men, 3.6 vs. 3.1 for women). An increased number of donations, shorter interdonation intervals, female sex, and younger age are associated with low ferritin levels on initial and repeat testing. Some recovery of ferritin occurred, but most low-ferritin donors continued to have low or borderline levels on retesting. Informing donors of low ferritin results had a long-lasting impact on return rates and donation frequency, requiring recruitment efforts to maintain adequacy of supply. Increasing the interdonation interval leads to some improvement in ferritin levels; more sustained efforts to encourage donors to improve iron intake are needed to achieve long-term benefit.

Iron deficiency among blood donors: experience from the Danish Blood Donor Study and from the Copenhagen ferritin monitoring scheme.

Blood components collected from blood donors are an invaluable part of modern-day medicine. A healthy blood donor population is therefore of paramount importance. The results from the Danish Blood Donor Study (DBDS) indicate that gender, number of previous donations, time since last donation and menopausal status are the strongest predictors of iron deficiency. Only little information on the health effects of iron deficiency in blood donors exits. Possibly, after a standard full blood donation, a temporarily reduced physical performance for women is observed. However, iron deficiency among blood donors is not reflected in a reduced self-perceived mental and physical health. In general, the high proportion of iron-deficient donors can be alleviated either by extending the inter-donation intervals or by guided iron supplementation. The experience from Copenhagen, the Capital Region of Denmark, is that routine ferritin measurements and iron supplementation are feasible and effective ways of reducing the proportion of donors with low haemoglobin levels.

Efficiency and safety of varying the frequency of whole blood donation (INTERVAL): a randomised trial of 45 000 donors

SummaryBackgroundLimits on the frequency of whole blood donation exist primarily to safeguard donor health. However, there is substantial variation across blood services in the maximum frequency of donations allowed. We compared standard practice in the UK with shorter inter-donation intervals used in other countries.MethodsIn this parallel group, pragmatic, randomised trial, we recruited whole blood donors aged 18 years or older from 25 centres across England, UK. By use of a computer-based algorithm, men were randomly assigned (1:1:1) to 12-week (standard) versus 10-week versus 8-week inter-donation intervals, and women were randomly assigned (1:1:1) to 16-week (standard) versus 14-week versus 12-week intervals. Participants were not masked to their allocated intervention group. The primary outcome was the number of donations over 2 years. Secondary outcomes related to safety were quality of life, symptoms potentially related to donation, physical activity, cognitive function, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin. This trial is registered with ISRCTN, number ISRCTN24760606, and is ongoing but no longer recruiting participants.Findings45 263 whole blood donors (22 466 men, 22 797 women) were recruited between June 11, 2012, and June 15, 2014. Data were analysed for 45 042 (99·5%) participants. Men were randomly assigned to the 12-week (n=7452) versus 10-week (n=7449) versus 8-week (n=7456) groups; and women to the 16-week (n=7550) versus 14-week (n=7567) versus 12-week (n=7568) groups. In men, compared with the 12-week group, the mean amount of blood collected per donor over 2 years increased by 1·69 units (95% CI 1·59–1·80; approximately 795 mL) in the 8-week group and by 0·79 units (0·69–0·88; approximately 370 mL) in the 10-week group (p<0·0001 for both). In women, compared with the 16-week group, it increased by 0·84 units (95% CI 0·76–0·91; approximately 395 mL) in the 12-week group and by 0·46 units (0·39–0·53; approximately 215 mL) in the 14-week group (p<0·0001 for both). No significant differences were observed in quality of life, physical activity, or cognitive function across randomised groups. However, more frequent donation resulted in more donation-related symptoms (eg, tiredness, breathlessness, feeling faint, dizziness, and restless legs, especially among men [for all listed symptoms]), lower mean haemoglobin and ferritin concentrations, and more deferrals for low haemoglobin (p<0·0001 for each) than those observed in the standard frequency groups.InterpretationOver 2 years, more frequent donation than is standard practice in the UK collected substantially more blood without having a major effect on donors' quality of life, physical activity, or cognitive function, but resulted in more donation-related symptoms, deferrals, and iron deficiency.FundingNHS Blood and Transplant, National Institute for Health Research, UK Medical Research Council, and British Heart Foundation.

Changes in hematological indices and lymphocyte subsets in response to whole blood donation in healthy male donors

Whole blood donation has immunomodulatory effects, and most of these have been observed at short intervals following blood donation. This study aimed to investigate the impact of whole blood donation on lymphocyte subsets over a typical inter-donation interval. Healthy male subjects were recruited to study changes in complete blood count (CBC) (n = 42) and lymphocyte subsets (n = 16) before and at four intervals up to 106 days following blood donation. Repeated measures ANOVA were used to compare quantitative variables between different visits. Following blood donation, changes in CBC and erythropoietin were as expected. The neutrophil count increased by 11.3% at 8 days (p < .001). Novel changes were observed in lymphocyte subsets as the CD4/CD8 ratio increased by 9.2% (p < .05) at 8 days and 13.7% (p < .05) at 22 days. CD16-56 cells decreased by 16.2% (p < .05) at 8 days. All the subsets had returned to baseline by 106 days. Regression analysis showed that the changes in CD16-56 cells and CD4/CD8 ratio were not significant (Wilk’s lambda = 0.15 and 0.94, respectively) when adjusted for BMI. In conclusion, following whole blood donation, there are transient changes in lymphocyte subsets. The effect of BMI on lymphocyte subsets and the effect of this immunomodulation on the immune response merit further investigation.

A large national study of ferritin testing in Canadian blood donors.

We assessed risk groups for iron deficiency and the feasibility and efficacy of ferritin testing in a large blood center. Donors were informed of possible testing in the predonation pamphlet. Plasma ferritin was measured on retention samples (n = 12,595) from representative clinics. Low-ferritin donors (<25 µg/L) were sent a letter and information sheet and not called for 6 months. Ferritin testing was repeated on 25% of donors; donor return rate and frequency were monitored. Low-ferritin donors represented 2.9% of first-time and reactivated (no donation in past 12 months) male donors, 32.2% of first-time and reactivated female donors, 41.6% of repeat male donors, and 65.1% of repeat female donors. A mean of 11.7 months after index donation, the return rate was 76% for normal and 58% for low-ferritin donors; returning low-ferritin donors had made approximately one fewer donation. Ferritin increased by 16.3 and 12.1 µg/L in male and female low-ferritin donors and decreased by 17 µg/L in male and female normal-ferritin donors. The minimum hemoglobin level will be increased to 130 g/L for male donors and the minimum interdonation interval changed to 84 days (four donations yearly) for female donors based on iron deficiency risk groups. Large-scale ferritin testing was feasible. Donors informed of low-ferritin results had a lower return rate, donated less often, and had an increase in ferritin on return, approximately 1 year after initial testing, compared to donors with normal ferritin results.

Analysis of the Factors Affecting the Interval between Blood Donations Using Log-Normal Hazard Model with Gamma Correlated Frailties.

Time to donating blood plays a major role in a regular donor to becoming continues one. The aim of this study was to determine the effective factors on the interval between the blood donations. In a longitudinal study in 2008, 864 samples of first-time donors in Shahrekord Blood Transfusion Center, capital city of Chaharmahal and Bakhtiari Province, Iran were selected by a systematic sampling and were followed up for five years. Among these samples, a subset of 424 donors who had at least two successful blood donations were chosen for this study and the time intervals between their donations were measured as response variable. Sex, body weight, age, marital status, education, stay and job were recorded as independent variables. Data analysis was performed based on log-normal hazard model with gamma correlated frailty. In this model, the frailties are sum of two independent components assumed a gamma distribution. The analysis was done via Bayesian approach using Markov Chain Monte Carlo algorithm by OpenBUGS. Convergence was checked via Gelman-Rubin criteria using BOA program in R. Age, job and education were significant on chance to donate blood (P<0.05). The chances of blood donation for the higher-aged donors, clericals, workers, free job, students and educated donors were higher and in return, time intervals between their blood donations were shorter. Due to the significance effect of some variables in the log-normal correlated frailty model, it is necessary to plan educational and cultural program to encourage the people with longer inter-donation intervals to donate more frequently.

Potential impact on blood availability and donor iron status of changes to donor hemoglobin cutoff and interdonation intervals.

A minimum male hemoglobin (Hb) level of 13.0 g/dL becomes a Food and Drug Administration requirement effective May 2016. In addition, extending whole blood (WB) interdonation intervals (IDIs) beyond 8 weeks has been considered to reduce iron depletion in repeat blood donors. This study estimates the impact these changes might have on blood availability and donor iron status. Six blood centers participating in Retrovirus Epidemiology Donor Study-II (REDS-II) collected information on all donation visits from 2006 to 2009. Simulations were developed from these data using a multistage approach that first sought to adequately reproduce the patterns of donor return, Hb and ferritin levels, and outcomes of a donor's visit (successful single- or double-red blood cell donation, deferral for low Hb) observed in REDS-II data sets. Modified simulations were used to predict the potential impact on the blood supply and donor iron status under different Hb cutoff and IDI qualification criteria. More than 10% of WB donations might require replacement under many simulated scenarios. Longer IDIs would reduce the proportion of donors with iron depletion, but 80% of these donors may remain iron-depleted if minimal IDIs increased to 12 or 16 weeks. Higher Hb cutoffs and longer IDIs are predicted to have a potentially large impact on collections but only a modest impact on donor iron depletion. Efforts to address iron depletion should be targeted to at-risk donors, such as iron supplementation programs for frequent donors, and policy makers should try to avoid broadly restrictive donation requirements that could substantially reduce blood availability.

Estimating the residual risk for HIV, HCV and HBV in different types of platelet concentrates in Germany

We estimated and compared the residual risks due to window-period donations for pooled and apheresis platelets in Germany using a modification of a previously described statistical model. This model directly utilizes the reported interdonation intervals before a positive donation and reflects in this aspect the look-back procedures used in haemovigilance. Data from the German National Blood Donor Surveillance System for the years 2006-2012, including reports about donations from repeat donors with confirmed positive test results for HIV, HCV and HBV, were used to estimate the risk of undetected infectious units for both pooled and apheresis platelets. Demographics of whole-blood and apheresis donors differed in age, gender, catchment area and interdonation interval. These differences impact on the prevalence and incidence of transfusion relevant infections and consequently the residual risk. The estimates for the residual risks for pooled and apheresis platelets were comparable. For HIV, there was no significant difference, for HCV apheresis platelets had a lower residual risk, whereas pooled platelets had a lower risk for undetected HBV infections. These findings do not support calls for a shift to an apheresis platelets-only policy in Germany.

The INTERVAL trial to determine whether intervals between blood donations can be safely and acceptably decreased to optimise blood supply: study protocol for a randomised controlled trial.

BackgroundAgeing populations may demand more blood transfusions, but the blood supply could be limited by difficulties in attracting and retaining a decreasing pool of younger donors. One approach to increase blood supply is to collect blood more frequently from existing donors. If more donations could be safely collected in this manner at marginal cost, then it would be of considerable benefit to blood services. National Health Service (NHS) Blood and Transplant in England currently allows men to donate up to every 12 weeks and women to donate up to every 16 weeks. In contrast, some other European countries allow donations as frequently as every 8 weeks for men and every 10 weeks for women. The primary aim of the INTERVAL trial is to determine whether donation intervals can be safely and acceptably decreased to optimise blood supply whilst maintaining the health of donors.Methods/DesignINTERVAL is a randomised trial of whole blood donors enrolled from all 25 static centres of NHS Blood and Transplant. Recruitment of about 50,000 male and female donors started in June 2012 and was completed in June 2014. Men have been randomly assigned to standard 12-week versus 10-week versus 8-week inter-donation intervals, while women have been assigned to standard 16-week versus 14-week versus 12-week inter-donation intervals. Sex-specific comparisons will be made by intention-to-treat analysis of outcomes assessed after two years of intervention. The primary outcome is the number of blood donations made. A key secondary outcome is donor quality of life, assessed using the Short Form Health Survey. Additional secondary endpoints include the number of ‘deferrals’ due to low haemoglobin (and other factors), iron status, cognitive function, physical activity, and donor attitudes. A comprehensive health economic analysis will be undertaken.DiscussionThe INTERVAL trial should yield novel information about the effect of inter-donation intervals on blood supply, acceptability, and donors’ physical and mental well-being. The study will generate scientific evidence to help formulate blood collection policies in England and elsewhere.Trial registrationCurrent Controlled Trials ISRCTN24760606, 25 January 2012.

Concerning iron balance in blood donors.

Concerning iron balance in blood donors.

Predictors of hemoglobin recovery or deferral in blood donors with an initial successful donation

Donation eligibility is based on hemoglobin (Hb) level among other factors. This study assesses factors that influence Hb levels among first-time (FT) donors returning for a second donation. Allogeneic FT donors who successfully donated a red blood cell (RBC)-containing donation on their index presentation and returned to donate at least once more between August 1, 2009, and July 31, 2012, were included. Interdonation intervals and delta Hb (subsequent donation - index donation value) were calculated. Multivariable logistic regression and survival analysis methods were used to determine factors associated with 1) Hb recovery to preindex donation value or 2) deferral at the second presentation. During the study, 135,040 FT donors returned to donate. Overall, 44% of donors returned with a Hb level at or above their index value (defined as recovery for this study), 48.1% for males and 39.9% for females. Logistic regression revealed that the factor most strongly associated with Hb recovery was index Hb, with lower Hb having much higher odds of recovery. Shorter interdonation intervals were associated with decreased likelihood of recovery. Certain demographic characteristics were also associated with higher odds of recovery. Factors associated with deferral were similar to the factors associated with recovery, except for donor sex. As early as the second blood donation, allogeneic donors can be differentiated into two subpopulations: those who recover to index Hb levels and those who do not. Current data routinely collected by US blood centers cannot reliably distinguish between the two groups.

Low hemoglobin deferral in blood donors

Low hemoglobin deferral occurs in about 10% of attempted whole blood donations and commonly is a consequence of iron deficiency anemia. Pre-menopausal women often have iron deficiency anemia caused by menstruation and pregnancy and have low hemoglobin deferral on their first donation attempt. Frequent donors also develop iron deficiency and iron deficiency anemia because blood donation removes a large amount of iron from the donor and the 56-day minimum inter-donation interval for donors in the United States is not sufficient for recovery of hemoglobin and iron stores. Other causes for low hemoglobin deferral range from a medically insignificant deferral of a woman with hemoglobin between 12.0 and 12.4 g/dL, which is within the normal reference range but below the 12.5 g/dL needed to donate blood, to anemia caused by an unrecognized malignancy in a "healthy" individual attempting to donate blood. The diverse causes of anemia in blood donors make it difficult to provide accurate information to donors about the cause of their low hemoglobin deferral and complicate implementation of programs to prevent them by blood collecting agencies. This article reviews how hemoglobin is measured and the demographics and causes of low hemoglobin deferral in blood donors. It provides recommendations for how blood collection agencies can provide donors with accurate information about the cause of their deferral and discusses programs that can be implemented to decrease these deferrals in regular donors.

A systematic review of factors associated with the deferral of donors failing to meet low haemoglobin thresholds

Blood donors attending a donation session may be deemed ineligible to donate blood due to a failure to meet low haemoglobin (Hb) thresholds. Several studies have identified factors associated with a donor falling below these Hb thresholds. A review of these factors will inform future prospective studies and form the basis for predictive models of deferral due to low Hb. Studies were identified by searching MEDLINE, EMBASE, The Cochrane Library and the WHO International Clinical Trials Registry from 1980 to September 2012. Demographic data, donor history, haematological/biological factors and the primary outcome of deferral due to low Hb were extracted. Analyses were descriptive and quantitative; pooled odds ratios (ORs) were obtained by meta-analysis. Fifty-five studies met the inclusion criteria. A consistently higher rate of low Hb deferral was reported in females compared with males; meta-analysis showed a significantly greater risk of deferral due to low Hb in females compared with males in studies with universal Hb thresholds for males and females (OR 14.91, 95% confidence interval (CI) 12.82-17.34) and in studies with sex-specific Hb thresholds (OR 8.19, 95% CI 4.88-13.74). Greater rates of deferral due to low Hb were also associated with increasing age, higher ambient temperature, low body weight, shorter inter-donation interval and in donors of Hispanic or African descent. This work will help to define the criteria that should be considered in any large scale study of blood donor deferral, especially those that measure or aim to change failure to meet low Hb thresholds.

Window period donations during primary cytomegalovirus infection and risk of transfusion‐transmitted infections

Donors with short interdonation intervals (e.g., apheresis donors) have an increased risk of window period donations. The frequency of cytomegalovirus (CMV) window period donations is important information to decide whether selection of seronegative donors might be advantageous for patients at risk for transfusion-transmitted CMV infections (TT-CMV). CMV seroconversion in 93 donors with positive results in routine CMV antibody testing within at most 35 days after the last seronegative sample was evaluated by Western blot and/or a second antibody test. In donors with unconfirmed seroconversion, an additional later sample was tested. Concentration of CMV DNA was determined in pre- and postseroconversion samples. CMV seroconversion was confirmed in 12 donors (13%). Among these, the last seronegative sample was CMV DNA positive in three donors (25%, below 30 IU/mL). The first seropositive sample was CMV DNA positive in 10 donors (83%, maximum 1600 IU/mL). Both prevalence and median concentration of CMV DNA were higher in the first seropositive sample (p = 0.004 and p = 0.02), with maximum concentrations being reached about 2 weeks after seroconversion. No CMV DNA was detected in samples from donors with unconfirmed seroconversion. At least in donors with short interdonation intervals, most suspected CMV seroconversions are due to false-positive results of the screening test. As window period donations are rare and contain less CMV DNA than the first seropositive donation, avoidance of blood products from primarily seropositive donors is especially helpful to avoid TT-CMV if donors with short interdonation intervals are concerned.

Prevalence of serologic markers for hepatitis B and C viruses in Brazilian blood donors and incidence and residual risk of transfusion transmission of hepatitis C virus

We evaluate the current prevalence of serologic markers for hepatitis B virus (HBV) and hepatitis C virus (HCV) in blood donors and estimated HCV incidence and residual transfusion-transmitted risk at three large Brazilian blood centers. Data on whole blood and platelet donations were collected from January through December 2007, analyzed by center; donor type; age; sex; donation status; and serologic results for hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen (anti-HBc), and anti-HCV. HBV and HCV prevalence rates were calculated for all first-time donations. HCV incidence was derived including interdonation intervals that preceded first repeat donations given during the study, and HCV residual risk was estimated for transfusions derived from repeat donors. There were 307,354 donations in 2007. Overall prevalence of concordant HBsAg and anti-HBc reactivity was 289 per 100,000 donations and of anti-HCV confirmed reactivity 191 per 100,000 donations. There were significant associations between older age and hepatitis markers, especially for HCV. HCV incidence was 3.11 (95% confidence interval, 0.77-7.03) per 100,000 person-years, and residual risk of HCV window-phase infections was estimated at 5.0 per million units transfused. Improvement in donor selection, socioeconomic conditions, and preventive measures, implemented over time, may have helped to decrease prevalence of HBV and HCV, relative to previous reports. Incidence and residual risk of HCV are also diminishing. Ongoing monitoring of HBV and HCV markers among Brazilian blood donors should help guide improved recruitment procedures, donor selection, laboratory screening, and counseling strategies.

Reasons for blood donation deferral in sub‐Saharan Africa: experience in Ivory Coast

Blood donor selection is important to ensure the safety of both donors and recipients. There is a paucity of data on reasons for blood donor deferral in Ivory Coast. The aim of this study was to identify the reasons for predonation deferral at a blood collection site at General Hospital, Yopougon Attié in Abidjan. The investigators conducted a retrospective audit of data pertaining to donor deferral for blood donors that presented to the general hospital of Yopugon Attié from January 1, 2006 to December 31, 2008. A total of 10,694 prospective blood donors, presented over the study period, and 24,363 attempts to donate were registered. The majority were repeat blood donors (77.4%). A total of 2618 (10.8%) donors were deferred. The most frequent reason for deferral was a low hemoglobin level (42.5%), with females constituting the majority of those deferred. The second most frequent reason for deferral was a reported change of or new sexual partner (34.3%); male donors were predominant in this group. Additional reasons for deferral included short interdonation interval (4.6%) and reactivity for a screened biomarker (2.3%). Although the rates for permanent and temporary deferral rates are similar between the Ivory Coast and high-middle income countries, the causes and demographics differ. The reasons for exclusion are preventable through awareness and education of prospective blood donors.

Demographic, laboratory, and operational variables that influence short‐ and long‐term plateletpheresis yields

We studied the demographic, laboratory, and operational parameters that might influence individual, as well as average, plateletpheresis yields. Multivariate linear regression analyses showed that 25.4% and 11.6% of variability, among males and females, respectively, in individual yields was explained by the platelet count prior to that donation and 55% of the variation in mean platelet yields (PYs) was explained by the pre-first donation platelet count, the first donation PY and the body mass index (BMI). Logistic regression analysis showed that donors with first donation PYs higher, compared to those with lower yields, than the median of all mean PYs were more likely to be relatively high platelet yielders over the long term. A statistically significant, although clinically insignificant, decline in predonation platelet counts is seen in all donors regardless of the total number of donations or interdonation interval. Donors with high pre-first donation platelet counts, first donation yields, and BMI are likely to be consistent good platelet yielders.

Effect of increasing hemoglobin cutoff in male donors and increasing interdonation interval in whole blood donors at a hospital‐based blood donor center

The NHANES-III survey found hemoglobin (Hb) concentrations of more than 13.5 g/dL and more than 12.0 g/dL in normal Caucasian males and females. In the United States, a Hb of least 12.5 g/dL is required for blood donation, which allows "anemic" males to donate while excluding "normal" females. Low Hb is the major cause of deferral in donors and deferrals are associated with decreased donor return rates. Additionally, frequent blood donations are associated with depletion of body iron stores. Analysis of the effect of various Hb cutoffs and interdonation intervals on our center's blood supply is presented. Whole blood donor data for a 12-month period were studied. Potential effects on the blood supply by increasing male Hb eligibility levels and/or increasing the interdonation interval were analyzed. A total of 13,519 individuals (females, 56%) donated 30,678 units (mean frequency, male 2.7 and females 2.1) with the majority (42%) donating once. Increasing the male Hb eligibility to at least 13.5 g/dL will decrease collections by 1457 (5%) units. In addition, decreasing the female Hb eligibility to at least 12.0 g/dL will result in total gain of 307 (1%) units. Considering 12-week interdonation interval and Hb eligibility of at least 13.5 g/dL (male) and at least 12.5 g/dL (female) results in decrease of 11% (3352) units. Increasing the Hb cutoff for male donors and/or interdonation interval for all donors will decrease available blood, some of which may be reduced by decreasing the Hb cutoff for females to at least 12.0 g/dL. As a majority of the donors donate only once with mean donation frequency being 2.4, it may be possible to overcome this shortfall by targeted recruitment of donors donating once.

Blood donation, blood supply, iron deficiency and anemia - It is time to shift attention back to donor health

Since the 1980s blood collectors worldwide have focused on two central themes: blood product safety and an adequate blood supply. From the standpoint of safety, specifically the reduction of transfusion-transmitted diseases, the achievements over the past quarter century are remarkable. With respect to the adequacy of the blood supply, the past decade has witnessed major gains in some countries of Europe, Canada and the US and less than had been expected in others, including Brazil, where the challenge of having a more stable blood supply, in which supply and demand are in better balance remains an important issue(1). On the other hand, the aforementioned achievement has come at a price: iron depletion of the repeat blood donor. Blood centers have long recognized that it is more effective and less expensive to collect blood from existing donors than to recruit new donors. While first-time donors, particularly the young and minorities, have been more successfully recruited, 70% of US and 40-70% (depending on the region) of Brazilian donors are repeat donors(1,2). The only known significant disadvantage of blood donation is the potential risk of iron deficiency (ID). Iron is a vitally important element in the human metabolism. It plays a central role in erythropoiesis and is also involved in many other intracellular processes in all the tissues of the body. The potentiality of the individual donor to give blood without developing ID and iron deficiency anemia (IDA) varies widely, probably due to differences in nutritional iron intake, the differences in prevalences of ID in each study population, menstrual iron loss in females, the frequency of blood donation and the use of supplemental iron(2). The frequency of ID is high in blood donors (1.8% to 8.4% in males and 4.5% to 34.8% in females), and more dependent on the frequency of donations than on the cumulated number of donations(2,4). In addition to this, ID is a significant problem and its prevalence is increasing in many countries around the world. The prevalence has been reported to be 9-40% in women, depending on age and menstrual status and 2-5% in men(1,2). Because menstruating females begin their blood donation careers from a lower starting point, subsequent donations pose a risk for greater clinical harm. Females have much higher rates of both ID and IDA.The clinical implications of ID and IDA are not insignificant, including fatigue, reduced work performance and intellectual capacity, reduced endurance, restless leg syndrome, pica, and cognitive and immune function changes. The degree of symptomatology is proportionate to the severity of the anemia(1,2). Moreover, low hemoglobin (Hb) accounts for 4-10% of total deferrals, with the vast majority occurring in women. Therefore it seems reasonable to secure adequate iron reserves in the donor population in order to maintain an appropriate donation potentiality and to avoid possible hematological and non-hematological complications related to ID(1,2). The question that arises is whether this practice is in the best interest of donor health. In this issue of Revista Brasileira de Hematologia e Hemoterapia, Silva et al., representing the Hemocentro Regional de Uberaba, Minas Gerais, Brazil, have brought this issue to light(5). Given the findings in this and other studies, what measures can blood collectors pursue to address iron depletion? There is no single answer, but several approaches should be considered: 1) modifying the donor Hb requirements and measurement of Hb, 2) changing the interdonation interval, 3) testing for serum ferritin, and 4) iron supplementation.

Hepcidin in Male Double Red Blood Cell Donors - Relationship Between Parameters of Iron Metabolism and Erythropoiesis

Abstract 2109Hemoglobin (Hb) below 12.5g/dL accounts for more than 40% of all blood donor deferrals, and no standardized message is provided to these deferred donors. Furthermore, many donors who meet Hb standards are iron depleted. In light of this, the FDA requested comments on possibly changing the minimal acceptable Hb and/or the inter-donation interval. Here we explore several parameters of iron utilization after red blood cell (RBC) donation to understand its relationship to erythropoiesis.Hepcidin is the central regulator of iron absorption, suppressed by low iron stores. We hypothesize that hepcidin values would identify donors with normal Hb levels and low iron stores and thus identify those who would benefit from iron replacement to prevent future low Hb deferral.We enrolled eligible repeat male double RBC donors randomized to receive placebo (n=5) or iron supplementation (n=5) using 90 mg of elemental iron (feosol caplets). Donors were enrolled on day of donation and were invited to return at 2–4 day intervals during the 14 days following donation to compare with pre-donation markers of erythropoiesis and iron metabolism. In addition, buffy coats were collected on day 0 and again 7–10 days following donation (n=6) to quantify by flow cytometry circulating CD34+ cells as well as numbers of common myeloid progenitors (CMPs) and megakaryocyte erythroid progenitors (MEPs) in study donors.Comparing iron supplemented to placebo receiving volunteers, ferritin was higher at 14 days in iron supplemented donors (18.6±3.9 vs 12.0±1.6 ng/mL) and corresponds with 52% vs. 36% of levels prior to donation relative to placebo (P=0.05). Furthermore, serum hepcidin nadirs earlier and rebounds sooner relative to placebo (15.4±3.2 vs. 6.8±2.1 ng/mL, P=0.05). Serum iron (150±37.1 vs. 60±5.8 mg/dL, P=0.04) and transferrin saturation (39.8±9.8 vs. 16.2±2.1%, P=0.05) are also increased relative to placebo by day 10 following donation. Although we found no difference in recovery of RBC count, hemoglobin, or hematocrit following donation, a trend toward a more sustained elevation in reticulocyte count is present relative to placebo (158±12.1 vs. 118±17.3 × 109 cells/mL, P=0.07). CD34+ cells in circulation are increased following donation in all donors. Furthermore, only donors with baseline ferritin levels >20 ng/mL increased MEPs following donation. These later findings are consistent with expectations of iron regulatory mechanisms influencing erythropoiesis.Taken together, these data suggest that a complex interplay between iron regulatory and erythropoietic mechanisms occurs during recovery from blood donation. Although it is currently unclear how iron regulation affects erythropoiesis, a larger (double) sample size will aid in the generation of criteria for donor iron supplementation. Disclosures:Olbina:Intrinsic LifeSciences LLC: Employment, Equity Ownership; Hepcidin C-ELISA:. Westerman:Intrinsic LifeSciences LLC: Employment, Equity Ownership, Membership on an entity’s Board of Directors or advisory committees; Hepcidin C-ELISA: Patents & Royalties; Centocor-Ortho R&D, Inc.: Honoraria.