Postdonation iron replacement for maintaining iron stores in female whole blood donors in routine donor practice: results of two feasibility studies in Australia.

BACKGROUND: Iron deficiency represents a risk to donor health and the blood supply. Efficacy trials indicate that postdonation iron replacement improves iron stores but they do not account for complexities of implementation in the routine collection context. We therefore conducted two prospective feasibility studies in Australian donor centers. STUDY DESIGN AND METHODS: In both studies we recruited female donors between 18 and 45 years who had made at least one donation in the previous 12 months. In READ (replacement advice), female donors were given a recommendation to self-procure postdonation iron. In DIRECT (donor iron replacement), donors were provided with a course of iron supplements. Donors could return to donate at their discretion and were surveyed after the recruitment visit and again toward the end of the 13-month follow-up. Donor uptake, adverse effects, effectiveness in maintaining iron stores, and workflow impact were assessed. RESULTS: We recruited 1404 (70.9% of invited) donors to READ and 768 (53.2% of invited) to DIRECT. READ and DIRECT extended predonation interviews by 1 and 5 minutes, respectively. Among participants, 44 and 88% took iron in READ and DIRECT, respectively. Adverse effects were common but usually mild. READ failed to maintain iron stores in the population, but was effective in donors who consumed more than 75% of the recommended dose. DIRECT was effective in preventing declines in ferritin concentration. CONCLUSION: Trade-offs between cost, complexity, uptake, and effectiveness must be considered in the implementation of postdonation iron supplementation.

The infectious disease blood safety risk of Australian hemochromatosis donations.

BACKGROUND: It has been suggested that blood donors with hereditary hemochromatosis may pose an increased infectious disease risk and adversely affect recipient outcomes. This study compares the infectious disease risk of whole blood (WB) donors enrolled as therapeutic (T) donors to voluntary WB donors to evaluate the safety of blood products provided by the T donors. STUDY DESIGN AND METHODS: This was a retrospective cohort study of all WB donations at the Australian Red Cross Blood Service who donated between January 1, 2011, and December 31, 2013, comparing a yearly mean of 11,789 T donors with 107,773 total donations and a yearly mean of 468,889 voluntary WB donors with 2,584,705 total donations. We compared postdonation notification of infectious illnesses, bacterial contamination screening results, and positive tests for blood borne viruses in T and WB donors. RESULTS: Rates of transfusion-transmissible infections in donations destined for component manufacture were significantly lower in therapeutic donations compared to voluntary donations (8.4 vs. 21.6 per 100,000 donations). Bacterial contamination (43.0 vs. 45.9 per 100,000 donations) and postdonation illness reporting (136.2 vs. 110.8 per 100,000 donations) were similar in both cohorts. CONCLUSIONS: The Australian therapeutic venisection program enables T donors to provide a safe and acceptable source of donated WB that has a low infectious disease risk profile.

Hepatitis E virus RNA in Australian blood donations.

BACKGROUND: Hepatitis E virus (HEV) poses a risk to transfusion safety. In Australia, locally acquired HEV is rare and cases are mainly reported in travelers returning from countries endemic for HEV. The risk posed by HEV to transfusion safety in Australia is unknown; therefore, we aimed to measure the rate of current HEV infection in Australian blood donations. STUDY DESIGN AND METHODS: A total of 14,799 blood donations were tested for HEV RNA by transcription-mediated amplification, with confirmatory testing by reverse transcription-polymerase chain reaction. Viral load quantification and phylogenetic analysis was performed on HEV RNA-positive samples. RESULTS: One (0.0068%; 95% confidence interval [CI], 0.0002%-0.0376%) sample was confirmed positive for HEV RNA, resulting in a risk of collecting a HEV-viremic donation of 1 in 14,799 (95% CI, 1 in 584,530 to 1 in 2,657). The viral load in this sample was approximately 15,000 IU/mL, and it was determined to be Genotype 3. DISCUSSION: Our finding of 1 in 14,799 Australian donations positive for HEV RNA is lower than that from many other developed countries; this is consistent with the relatively low seroprevalence in Australia. As this HEV RNA-positive sample was Genotype 3, it seems likely that this infection was acquired through zoonotic transmission, either within Australia or overseas in a developed nation. HEV has the potential to pose a risk to transfusion safety in Australia; however, additional, larger studies are required to quantify the magnitude of this risk.

An 8-week course of 45 mg of carbonyl iron daily reduces iron deficiency in female whole blood donors aged 18 to 45 years: results of a prospective randomized controlled trial.

BACKGROUND: Blood donation is known to contribute to iron deficiency in regular blood donors. This study investigated the safety and efficacy of postdonation iron replacement to mitigate iron deficiency in blood donors. STUDY DESIGN AND METHODS: A total of 282 female whole blood donors aged 18 to 45 were prospectively randomized in a double-blinded placebo controlled trial to receive an 8-week postdonation course of carbonyl iron (45 mg daily) or placebo. The primary endpoint was prevalence of iron deficiency (ferritin < 15 ng/mL) at 12 weeks postdonation. Secondary endpoints were eligibility to donate based on capillary hemoglobin (Hb) and incidence of gastrointestinal (GI) complaints. RESULTS: Ferritin levels at Week 12 were significantly higher in donors receiving carbonyl iron (17.0 ± 10.9 ng/mL) compared with those receiving placebo (10.6 ± 8.4 ng/mL; p < 0.001). The proportion of iron-deficient donors was significantly lower in the carbonyl iron group (51.9%) compared to the placebo (80.5%; p < 0.001). The mean Hb level in the carbonyl iron group (134.6 ± 8.7 g/L) was significantly higher than in the placebo arm (130.0 ± 9.9 g/L; p < 0.001), significantly improving eligibility to donate at Week 12. Significantly more donors receiving carbonyl iron had at least one GI side effect (p < 0.001). Importantly, 86.7% of donors receiving carbonyl iron indicated that they would take iron on an ongoing basis. CONCLUSION: An 8-week postdonation course of 45 mg of carbonyl iron significantly reduced iron deficiency and was well tolerated in female whole blood donors. Postdonation iron replacement may have a role in a broader strategy to optimize donor iron status.

Iron status and dietary iron intake of female blood donors.

BACKGROUND: The aim was to assess iron status and dietary iron intake in a sample of premenopausal female regular and new blood donors. STUDY DESIGN AND METHODS: Premenopausal women blood donors were invited to participate. Blood samples were analyzed for serum ferritin and hemoglobin. An iron checklist assessed dietary iron intake. Donors were classified as regular donors or new donors. RESULTS: Twenty-one new donors (mean [SD] age, 28.6 [6.0] years; body mass index [BMI], 25.6 [4.5] kg/m(2) ) and 172 regular donors (mean age, 29.4 [5.5] years; BMI, 24.7 [3.8] kg/m(2) ) participated. Fifty percent of regular donors and 24% of new donors had depleted iron stores (serum ferritin <15 µg/L; difference p = 0.036). Dietary iron intake was higher in regular donors (mean [SE], 12.6 [0.7] mg/day) compared to new donors (9.9 [0.4] mg/day; p = 0.006). Eighty-five percent of regular donors and 79% of new donors met the estimated average requirement for iron. CONCLUSIONS: Despite the fact that most of these donors had an adequate dietary iron intake, more than half of the blood donors had depleted iron stores. Increasing dietary iron intake through supplements and/or dietary means is expected to be necessary to maintain adequate iron status in this group.

A refined method for estimating the size of the potential blood donor pool in Australia.

BACKGROUND: To be eligible to donate blood, potential donors must meet certain eligibility criteria to ensure safety to the donor and to the blood supply. In Australia, there is no reliable estimate of the size of the donor-eligible population. This study uses a refinement to a published method to determine the population prevalence of donor-exclusion factors and subsequently estimates the size of the potential donor pool in Australia. STUDY DESIGN AND METHODS: A total of 70 donor-exclusion factors (in addition to age) were identified. The donor-eligible population was estimated by subtracting the prevalence of the exclusion factors from the total population. Prevalence of the donor-exclusion factors was adjusted for age, deferral period, and overlap of multiple conditions. Overlap was adjusted by extending a published random-probability model according to known association of epidemiologic data on overlapping conditions. RESULTS: The most prevalent (deferral period-adjusted) donor-exclusion factor among the 16- to 80-year-old Australian population was variant Creutzfeldt-Jakob disease-related travel risk (6.8%) followed by upper respiratory tract infections (6.4%). After exclusion of all factors, and accounting for overlapping factors, 62% of 16- to 80-year-olds or 47.3% of the total population were donor eligible in Australia. CONCLUSION: We developed a refined method for estimating the size of the donor-eligible population. Applying this method to Australia, we estimate that approximately 10.7 million people (62% of the 16- to 80-year-olds) were eligible to donate blood in Australia in 2012.

Understanding noncompliance with selective donor deferral criteria for high-risk behaviors in Australian blood donors.

BACKGROUND: Using a predonation screening questionnaire, potential blood donors are screened for medical or behavioral factors associated with an increased risk for transfusion-transmissible infection. After disclosure of these risks, potential donors are deferred from donating. Understanding the degree of failure to disclose full and truthful information (termed noncompliance) is important to determine and minimize residual risk. This study estimates the prevalence of, and likely reasons for, noncompliance among Australian donors with the deferrals for injecting drug use, sex with an injecting drug user, male-to-male sex, sex worker activity or contact, and sex with a partner from a high-HIV-prevalence country. STUDY DESIGN AND METHODS: An anonymous, online survey of a nationally representative sample of Australian blood donors was conducted. Prevalence of noncompliance with deferrable risk categories was estimated. Factors associated with noncompliance were determined using unadjusted and adjusted odds ratios. RESULTS: Of 98,044 invited donors, 30,790 donors completed the survey. The estimated prevalence of overall noncompliance (i.e., to at least one screening question) was 1.65% (95% confidence interval CI, 1.51%-1.8%). Noncompliance with individual deferrals ranged from 0.05% (sex work) to 0.54% (sex with an injecting drug user). The prevalences of the disclosed exclusionary risk behaviors were three to 14 times lower than their estimated prevalence in the general population. CONCLUSION: The prevalence of noncompliance is relatively low but our estimate is likely to be a lower bound. The selected high-risk behaviors were substantially less common in blood donors compared to the general population suggesting that self-deferral is effective. Nevertheless, a focus on further minimization should improve the blood safety.

Trends in transfusion-transmissible infections among Australian blood donors from 2005 to 2010.

BACKGROUND: Routine monitoring of trends in transfusion-transmissible infections (TTIs) is essential to maintaining and improving transfusion safety. Although periodic studies have been published there is no comprehensive trend analysis for TTIs in Australian donors. This study determined recent trends in TTIs for which testing is conducted in Australia and described key attributes of infected blood donors. STUDY DESIGN AND METHODS: This is a retrospective analysis using data on donation testing for TTIs (2005-2010) from the national blood service donor database and data on postdonation interviews with TTI-positive donors (2008-2010) from a risk factor database incorporating responses to standardized interview questions. The study measured the prevalence and incidence of TTIs in Australia and assessed their time trends. Multivariate analysis of time trends was conducted using Poisson regression models. RESULTS: Overall, the prevalence and incidence of TTIs in 2005 to 2010 remained low and steady. The prevalence of hepatitis C virus decreased (rate ratio [RR], 0.93; 95% confidence interval [CI], 0.89-0.97) and the prevalence of active syphilis increased (RR, 1.51; 95% CI, 1.15-1.99) significantly during the study period. Prevalence of TTIs among Australian blood donors was substantially lower than that in the general population and no unique risk factors were identified in test-positive blood donors when compared with the general population. CONCLUSION: Both the prevalence and the incidence of TTIs in Australian blood donors remained low, with a steady or declining trend for most infections except active syphilis. The lower prevalence of TTIs in blood donors compared with the general population reflects the effectiveness of donor education and donor selection measures in Australia.

A prospective trial assessing the safety and efficacy of collecting up to 840 mL of plasma in conjunction with saline infusion during plasmapheresis.

BACKGROUND: The demand for plasma for manufacturing intravenous immunoglobulin and other plasma derivatives is increasing. A prospective study was conducted to determine whether up to 840 mL of plasma could be safely and effectively collected in conjunction with saline infusion during plasmapheresis. STUDY DESIGN AND METHODS: Ninety-one plasma donors were enrolled in a modified 3 × 3 crossover study to assess the equivalence of three plasma collection methods: 750 mL of plasma with no saline (control, Method 1), 840 mL of plasma with a 250-mL saline infusion during and at the end of the donation (Method 2), and 800 mL of plasma with a 500-mL saline infusion at the end of the donation (Method 3). The primary efficacy endpoint was the total protein concentration of the collected plasma. Secondary efficacy endpoints were immunoglobulin (Ig)G and Factor (F)VIII plasma concentration and donors' acceptance of the new procedures. Safety was determined from the adverse event (AE) rate. RESULTS: The total protein, IgG, and FVIII concentrations in plasma collected under Methods 2 and 3 were significantly lower than those in plasma collected under Method 1 (p < 0.0001). These variables were also significantly lower in plasma collected under Method 2 compared to Method 3. During the study, 75 AEs were recorded, 73 of which were mild to moderate. Significantly more donors (31%) preferred Method 2 compared to Method 3 (p = 0.006). CONCLUSIONS: Saline infusion during plasmapheresis led to hemodilution of plasma proteins. However, the benefits to donor safety and satisfaction are compelling reasons to implement saline infusion during plasmapheresis.

Serum hepcidin as a diagnostic test of iron deficiency in premenopausal female blood donors.

BACKGROUND: Currently used indicators of iron status have limitations. Hepcidin, a key regulator of iron metabolism, is reduced in iron deficiency. We sought to determine the properties of hepcidin as a diagnostic test of iron deficiency. DESIGN AND METHODS: Sera from female, non-anemic, whole blood donors were analyzed for hepcidin (enzyme-linked immunosorbent assay), ferritin, soluble transferrin receptor and C-reactive protein. Iron deficiency was defined as (i) serum ferritin less than 15 ng/mL or (ii) soluble transferrin receptor /log(ferritin) index greater than 3.2 if the C-reactive protein concentration was less than 10 mg/L, or greater than 2.2 if the C-reactive protein concentration was greater than 10 mg/L). Receiver operating characteristic curves were plotted to determine the overall utility and identify optimal cut-points of hepcidin as a test of iron deficiency. RESULTS: In 261 blood donors the prevalence of iron deficiency defined by ferritin concentration was 59/261 [22.6% (17.5, 27.7)], whereas defined by soluble transferrin receptor/log(ferritin) index it was 53/261 [20.4% (15.4, 25.2)]. The 95% reference range of hepcidin concentration in the iron-replete population was 8.2-199.7 ng/mL. The area under the receiver operating characteristic curve for hepcidin compared with ferritin concentration less than 15 ng/mL was 0.87 (0.82, 0.92), while that compared with the soluble transferrin receptor /log(ferritin) index was 0.89 (95% CI 0.84, 0.93). For a diagnosis of iron deficiency defined by the soluble transferrin receptor/log(ferritin) index, hepcidin less than 8 ng/mL had a sensitivity of 41.5% and a specificity of 97.6%, while hepcidin less than 18 ng/mL had a sensitivity of 79.2% and a specificity of 85.6%. CONCLUSIONS: Serum hepcidin concentration may be a useful indicator of deficient iron stores. Further studies are required to evaluate the role of hepcidin in the diagnosis of iron deficiency in other groups of patients.

Hemoglobin and iron indices in nonanemic premenopausal blood donors predict future deferral from whole blood donation.

BACKGROUND: Iron deficiency anemia is an important reason for blood donor deferral. We prospectively determined whether screening donors with hemoglobin (Hb) and iron indices before donation can predict subsequent deferral due to anemia. STUDY DESIGN AND METHODS: We recruited premenopausal, eligible (nonanemic) female donors. Hb, ferritin, soluble transferrin receptor (sTfR), and hepcidin were measured, and the sTfR/(log)ferritin (sTfR-F) index was calculated. After 6 months, the donor database was reviewed and whether donors had returned and undergone successful donation was recorded. RESULTS: Of donors, 59 of 261(22.6%) were iron depleted (ferritin < 15 ng/mL). Iron-depleted donors had donated more often in the previous year, were younger, and had lower Hb. After a minimum of 6 months, 145 eligible donors had returned; of these 10 (6.9%) were deferred for anemia. Donors who developed anemia had significantly lower Hb, ferritin, and hepcidin and higher sTfR and sTfR-F at baseline. The area under the receiver operating characteristic curve for Hb as a predictor of deferral was 0.86, and for ferritin was 0.88. Hb of less than 130 g/L and ferritin of less than 10 ng/mL combined had sensitivity 80% and specificity 96% in predicting deferral. CONCLUSION: Screening with Hb and iron indices enables prediction of donors at risk of subsequent anemia and who would most benefit from prevention strategies.

No evidence of a significantly increased risk of transfusion-transmitted human immunodeficiency virus infection in Australia subsequent to implementing a 12-month deferral for men who have had sex with men.

BACKGROUND: Male-to-male sex is the predominant route of human immunodeficiency virus (HIV) transmission in Australia and since the early 1980s blood services in Australia have deferred donors for this practice for at least 5 years. This retrospective analysis assesses the impact on HIV prevalence of implementing an abridged 12-month deferral for male-to-male sex. STUDY DESIGN AND METHODS: The prevalence of HIV among blood donors for 5-year periods before (Period 1) and after (Period 2) implementing the revised 12-month deferral was compared. Using deidentified data from postdonation interviews with HIV-positive donors the proportion disclosing male-to-male sex as a risk factor was compared for the two periods. RESULTS: Twenty-four HIV-positive donations were identified among 4,025,571 donations in Period 1 compared with 24 among 4,964,628 donations in Period 2 (p=0.468). The proportion of HIV-positive donors with male-to-male sex as a risk factor in Period 1 was 2 in 15 (13.3%), which was not significantly different from the proportion in Period 2, 5 in 16 (31.25%; p=0.22). All five men who have sex with men risk HIV infections during Period 2 were from donors whose risk was within the 12-month criterion for acceptability, who would have been deferred had they provided a complete history. CONCLUSIONS: We found no evidence that the implementation of the 12-month deferral for male-to-male sex resulted in an increased recipient risk for HIV in Australia. The risk of noncompliance to the revised deferral rather than its duration appears to be the most important modifier of overall risk.

The risk of dengue transmission by blood during a 2004 outbreak in Cairns, Australia.

BACKGROUND: Dengue virus (DENV) is a Flavivirus transmitted by the Aedes mosquito. The related arbovirus, West Nile virus, has been shown to be transfusion transmitted, which, added to the four recorded dengue transfusion-associated cases, indicates that DENV is also transfusion transmitted. The purpose of this study was to assess the risk of transfusion-transmitted DENV during a 2004 outbreak in the Australian city of Cairns. STUDY DESIGN AND METHODS: A mathematical model was constructed to estimate the risk of transfusion-transmitted dengue. The model's central premise is that the transmission risk is proportional to the frequency of dengue-viremic donations and correlates with the incidence of asymptomatic dengue viremia among the population at large. RESULTS: The modeling predicted that the total number of DENV infections (clinical plus subclinical) among the population at large during the entire outbreak ranged from 156 to 569 with the epidemic peak occurring between February 8 and March 6, 2004. The overall transmission risk during the entire outbreak was estimated as 1 in 19,759 (range, 1 in 3404 to 75,486) peaking at 1 in 5968 (range 1 in 1028 to 22,800). CONCLUSION: By use of the most conservative estimates for key variables, the risk of collecting a viremic donation could have been as high as 1 in 1028 during the peak of the 2004 outbreak. The model can be used to determine transfusion transmission risk levels during DENV outbreaks and inform decisions as to when fresh component restriction measures are required to minimize transfusion transmission risk.

Emerging viral threats to the Australian blood supply.

OBJECTIVES: To assess the risk to the Australian blood supply posed by emerging or re-emerging viral infections. METHOD: A review was undertaken of the English-speaking literature on the potential for emerging viral threats to human health in Australia, the future implications of virus ecology, climate change and population movement and the implications for blood transfusion. RESULTS: Published data confirm that Australia's blood supply is among the safest in the world for currently screened viral pathogens as a result of rigorous surveillance, donor selection and state-of-the-art processing and laboratory testing. However, Australia has a number of other viral pathogens with the potential to threaten the safety of the blood supply such as the Ross River, Barmah Forrest, Kunjin, Japanese Encephalitis, Murray Valley Encephalitis and dengue viruses. Of these, dengue is currently of most concern to blood safety because; it can cause fatalities, there are regular seasonal outbreaks in Northern Australia and, in contrast to other viruses mentioned above an overseas case of transfusion transmission has already been documented. Notably, despite the lack of a suitable dengue screening test the ARCBS already implements supplementary measures to protect the blood supply during outbreaks. CONCLUSION: Current interventions have proven extremely effective in minimising transfusion transmission in Australia of recognised viral pathogens. The threat posed by emerging viral pathogens to the safety of blood transfusion emphasises the need for global collaboration and consideration of further intervention strategies on a country by country basis including options such as nucleic acid testing and pathogen reduction technologies.

Re-examining blood donor deferral criteria relating to injecting drug use.

BACKGROUND AND AIMS: Potential Australian blood donors are deferred indefinitely if they report a history of injecting drug use (IDU), or for 12 months if they report having engaged in sexual activity with someone who might have ever injected. Given incremental improvements in blood safety, this study sought to examine whether Australia's IDU-related eligibility criteria reflected current scientific evidence, were consistent with international best practice and, if current IDU-related policies were to be changed, how this should happen. METHODS: An expert committee was formed to review relevant literature with a focus on issues including: the epidemiology of IDU in Australia and key transfusion-transmissible infections (TTIs) among Australian people who inject drugs (PWID); and, 'non-compliance' among PWID regarding IDU-related blood donation guidelines. International policies relating to blood donation and IDU were also reviewed. Modelling with available data estimated the risk of TTIs remaining undetected if the Blood Service's IDU-related guidelines were changed. RESULTS: Very few (<1%) Australians engage in IDU, and IDU risk practices are reported by only a minority of PWID. However, the prevalence of HCV remains high among PWID, and IDU remains a key transmission route for various TTIs. Insufficient data were available to inform appropriate estimates of cessation and relapse among Australian PWID. Modelling findings indicated that the risk of not detecting HIV becomes greater than the reference group at a threshold of non-admission of being an active PWID of around 1.8% (0.5-5.1%). Excluding Japan, all Organisation for the Economic Co-operation and Development member countries permanently exclude individuals with a history of IDU from donating. CONCLUSION: Numerous research gaps meant that the study's expert Review Committee was unable to recommend altering Australia's current IDU-related blood donation guidelines. However, having identified critical knowledge gaps and future areas of research, the review made important steps toward changing the criteria.

Hepatitis E virus infections in travellers: assessing the threat to the Australian blood supply.

BACKGROUND: In many developed countries hepatitis E virus (HEV) infections have occurred predominantly in travellers to countries endemic for HEV. HEV is a potential threat to blood safety as the virus is transfusion-transmissible. To minimise this risk in Australia, individuals diagnosed with HEV are deferred. Malarialdeferrals, when donors are restricted from donating fresh blood components following travel toanareain which malaria is endemic, probably also decrease the HEV risk, by deferring donors who travel to many countries also endemic for HEV. The aim of this study is to describe overseas-acquired HEV cases in Australia, in order to determine whether infection in travellers poses a risk to Australian blood safety. MATERIALS AND METHODS: Details of all notified HEV cases in Australia from 2002 to 2014 were accessed, and importation rates estimated. Countries in which HEV was acquired were compared to those for which donations are restricted following travel because of a malaria risk. RESULTS: Three hundred and thirty-two cases of HEV were acquired overseas. Travel to India accounted for most of these infections, although the importation rate was highest for Nepal and Bangladesh. Countries for which donations are restricted following travel due to malaria risk accounted for 94% of overseas-acquired HEV cases. DISCUSSION: The vast majority of overseas-acquired HEV infections were in travellers returning from South Asian countries, which are subject to donation-related travel restrictions for malaria. This minimises the risk HEV poses to the Australian blood supply.