Retrovirus Epidemiology Donor Study-II Research Articles

Physiologically based serum ferritin thresholds for iron deficiency in women of reproductive age who are blood donors

AbstractOur objective is to develop a physiologically based method to determine serum ferritin thresholds for iron deficiency in healthy individuals. The current World Health Organization threshold of <15 µg/L for iron deficiency in women is based on expert opinion. We examined the relationship between serum ferritin and 2 independently measured indicators of iron-deficient erythropoiesis, soluble transferrin receptor (sTfR) and hemoglobin, in baseline data from 286 women, 20 to 49 years, who were first-time or reactivated donors in the Retrovirus Epidemiology Donor Study-II Donor Iron Status Evaluation (REDS-RISE) study. At lower serum ferritin concentrations, median sTfR increased as hemoglobin decreased. Using restricted cubic spline regression analysis to determine thresholds for iron-deficient erythropoiesis, the thresholds identified by sTfR (serum ferritin < 25.4 µg/L) and hemoglobin (serum ferritin < 25.3 µg/L) did not differ significantly. The thresholds found in the REDS-RISE study do not differ from those identified by sTfR (serum ferritin < 25.5 µg/L) and hemoglobin (serum ferritin < 26.6 µg/L) in a previous study of 5442 women, 20 to 49 years, in the US National Health and Nutrition Examination Survey 2003 to 2018 (P = .98 and 0.83, respectively). Although international comparisons are needed, these results with US data provide additional evidence for the potential usefulness of a physiologically based method to identify serum ferritin thresholds for iron deficiency.

Deriving a parsimonious cardiac endpoint for use in epidemiological studies of Chagas disease: results from the Retrovirus Epidemiology Donor Study-II (REDS-II) cohort.

ABSTRACTChagas cardiomyopathy (ChCM) is a severe consequence of Trypanosoma cruzi infection and has a range of electrocardiographic (ECG) and echocardiographic (ECHO) manifestations. There is a need for a standard and parsimonious research cardiac end point that does not rely on expert panel adjudication, and it is not intended to change the ChCM definition. We use data from the REDS-II cohort to propose a simplified cardiac endpoint. A total of 499 T. cruzi-seropositive blood donors were included. All participants underwent a 12-lead ECG, echocardiogram and clinical examination, and those with abnormal findings were reviewed by a panel of cardiologists who classified cases as having Chagas cardiomyopathy or not. We created an exhaustive set of ECG and ECHO finding combinations and compared these with the panel’s classification. We selected the simplest combination that most accurately reproduced the panel’s results. Individual ECG and ECHO variables had low sensitivity for panel-defined cardiomyopathy. The best performing combination was right bundle branch block and/or ECHO evidence of left ventricular hypocontractility. This combination had 98% specificity and 85% sensitivity for panel-defined ChCM. It was not possible to improve the overall accuracy by addition of any other ECG or ECHO variable. Substituting right bundle branch block for the more inclusive finding of QRS interval > 120 ms produced similar results. The combination of prolonged QRS interval and/or left ventricular hypocontractility closely reproduced the REDS-II expert panel classification of Chagas ChCM. In conclusion, the simple and reproducible research endpoint proposed here captures most of the spectrum of cardiac abnormalities in Chagas disease.

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.

The TMPRSS6 Ala736 Val Polymorphism Is Associated With Decreased Hemoglobin and Iron Status In Females Undergoing Repeated Phlebotomy

BackgroundIron depletion and deferral for low hemoglobin occur rapidly in some donors while others can repeatedly donate without deferral. This variation may be partly explained by significant genetic differences that affect regulation of dietary iron absorption and/or hemoglobin level following blood donation. Previous studies have found that the C282Y and H63D hemochromatosis mutations do not improve dietary iron absorption following donation. TMPRSS6 is a membrane-associated serine protease that degrades hemojuvelin, thereby decreasing hepcidin production with consequent increase in dietary iron absorption. Its physiological importance is best demonstrated by the development of iron resistant iron deficiency anemia in those with TMPRSS6 mutations. A common TMPRSS6 polymorphism, A736V (rs855791), is associated with lower hemoglobin, MCV and transferrin saturation. Its correlation with iron status and hemoglobin production was examined in blood donors undergoing repeated phlebotomy. MethodsThree sample sets from blood donors with well-characterized demographics, blood donation history, hemoglobin and iron parameters enrolled in the approximately 2-year longitudinal Retrovirus Epidemiology Donor Study-II (REDS-II) Iron Status Evaluation Study (RISE) were selected from the NHLBI BioLINCC repository: (Set 1) a random sample of 200 male and 200 female first-time donors and donors reactivated at study enrollment (no donations for 2 years); (Set 2) 114 first-time females who became “frequent” donors by donating at least 4 times in a 2-year period; and (Set 3) 33 repeat male donors, who were deferred for low hemoglobin during the study. Genetic testing for the TMPRSS6 A736V polymorphism was performed on donors in all 3 sets. Variation of hemoglobin and iron status among genotypes, adjusted for donor age, weight, race/ethnicity, number of donations in the previous 12 months and length of time between donations, was assessed using linear models. ResultsGenotypic frequencies in Set 1 were 40% AA, 42% A/V and 18% VV. The prevalence was not statistically different in the other two sets of donors, although there was a trend for higher prevalence of VV (30%) in Set 3. Hemoglobin, log-transformed ferritin and body iron stores (calculated based on ferritin and soluble transferring receptor) varied among TMPRSS6 genotypes in females but not in males. For females, average hemoglobin was 0.75 and 0.53 g/dL higher in AA (p<0.0001) and A/V (p=0.0057) than in VV. Average ferritin was 75% and 53% higher in AA (p=0.0024) and A/V (p=0.022) than in VV. Average body iron stores were 2.2 mg/kg and 1.8 mg/kg higher in AA (p=0.0045) and AV (p=0.022) than in VV. For males, average hemoglobin was only 0.13 g/dL higher in AA (p=0.47) and 0.035 g/dL lower in A/V (p=0.83) than in VV. Average ferritin was only 15% higher in AA (p=0.46) and was 8% lower in A/V (p=0.83) than in VV. Average body iron stores were 0.84 mg/kg higher in AA (p=0.10) and 0.15 mg/kg lower in A/V (p=0.75) than in VV. Due to the differences found in females, the longitudinal models were repeated using Set 2 subjects, which confirmed a significant association of the TMPRSS6 polymorphism with hemoglobin in females; 0.50 and 0.35 g/dL higher in AA (p<0.0037) and A/V (p=0.0255) than in VV. However, trends for effects on ferritin and body iron stores did not reach significance. Plasma hepcidin values were also available for Set 2 subjects, but significant differences among TMPRSS6 genotypes were not found. ConclusionsThe A736V TMPRSS6 polymorphism is associated with significant differences in hemoglobin and iron status of first-time female blood donors after undergoing iron loss from repeated phlebotomy. The apparent difference between males and females in variation among genotypes may be the result of greater baseline iron depletion in females rather than a gender difference per se. This is the first demonstration of an association between a common polymorphism of iron metabolism and altered individual responses to blood donation. The findings are consistent with a model in which the TMPRSS6 genotypes differ in proteolytic activity towards hemojuvelin, thereby altering hepcidin production and dietary iron absorption in otherwise healthy, but iron depleted individuals. Disclosures:Mast:Novo Nordisk: Honoraria, Research Funding.

An analysis of risk factors for human immunodeficiency virus infection among Chinese blood donors.

Information regarding the risk factors for human immunodeficiency virus (HIV) infection among Chinese donors is important for understanding the trend of HIV transmission routes and for developing effective donor behavioral screening policies. In 2009 to 2011, a total of 77 HIV-positive and 649 HIV-negative consented donors who screened nonreactive for hepatitis B virus, hepatitis C virus, syphilis, and alanine aminotransferase in four Retrovirus Epidemiology Donor Study-II Chinese regions received and completed a questionnaire by mail regarding their recent and past medical procedures, drug use, and sexual behaviors, etc. Exploratory and confirmatory factor analyses grouped questions into three risk factors. Multivariable logistic regression analysis examined the relationship between risk factors and HIV status adjusting for center, age, sex, and education. The three risk factors were test-seeking tendency, medical-related risks, and behavioral risks. In multivariable logistic regression analysis, greater test-seeking tendency and behavioral risks were associated with HIV infection, with the adjusted odds ratios (ORs) being 2.2 (95% confidence interval [CI], 1.2-4.1) and 3.8 (95% CI, 1.8-7.9), respectively, but medical risks were not (OR, 1.2; 95% CI, 0.6-2.2). In comparison to less high school education, high school and more education was associated with lower risks for HIV infection, with the ORs being 0.35 (95% CI, 0.17-0.70) and 0.17 (95% CI, 0.09-0.33), respectively. Test-seeking tendency and high-risk sexual behaviors are important predictors of HIV infection in Chinese blood donors, suggesting that the health history inquiry used in donor selection process needs improvement to defer high-risk donors more effectively.

Laboratory variables for assessing iron deficiency in REDS-II Iron Status Evaluation (RISE) blood donors.

Iron deficiency is common in regular blood donors. We evaluated the diagnostic sensitivity and specificity of red blood cell (RBC) hematology analyzer indices to assess iron status as a part of donor management. A total of 1659 male and female donors from the Retrovirus Epidemiology Donor Study-II (REDS-II) Donor Iron Status Evaluation (RISE) study who were either first-time/reactivated (FT/RA; no donations for 2 years) or frequent donors were recruited into a longitudinal study of regular donation of RBCs. Of these, 1002 donors returned 15 to 24 months later for a final assessment. Absent iron stores (AIS) was defined as plasma ferritin level of less than 12 μg/L. Logarithm of the ratio of soluble transferrin receptor to ferritin of at least 2.07 (≥97.5% in FT/RA males) was used to define iron-deficient erythropoiesis (IDE). Receiver operating characteristics analysis was performed to assess selected RBC indices (e.g., percentage of hypochromic mature RBCs, proportion of hypochromic mature RBCs [HYPOm], and hemoglobin [Hb] content of reticulocytes [CHr]) in identifying AIS and IDE. HYPOm and CHr detected IDE with comparable sensitivity, 72% versus 69%, but differed in specificity: HYPOm 68% and CHr 53%. For detecting AIS, sensitivity was improved to 85% for HYPOm and 81% for CHr but specificity was reduced for both. Venous Hb had high specificity but poor sensitivity for IDE and AIS. A plasma ferritin level of less than 26.7 μg/L was a good surrogate for assessing IDE. RBC indices correlate with AIS and IDE and are more informative than Hb measurement, but lack sufficient sensitivity and specificity to be used as diagnostic tools in blood donors at risk for iron deficiency.

Difficult blood donor choices: dance, feast or donate blood?

Difficult blood donor choices: dance, feast or donate blood?

The National Heart, Lung, and Blood Institute retrovirus epidemiology donor studies (Retrovirus Epidemiology Donor Study and Retrovirus Epidemiology Donor Study-II): twenty years of research to advance blood product safety and availability.

The Retrovirus Epidemiology Donor Study (REDS), conducted from 1989 to 2001, and the REDS-II, conducted from 2004 to 2012, were National Heart, Lung, and Blood Institute-funded, multicenter programs focused on improving blood safety and availability in the United States. The REDS-II also included international study sites in Brazil and China. The 3 major research domains of REDS/REDS-II have been infectious disease risk evaluation, blood donation availability, and blood donor characterization. Both programs have made significant contributions to transfusion medicine research methodology by the use of mathematical modeling, large-scale donor surveys, innovative methods of repository sample storage, and establishing an infrastructure that responded to potential emerging blood safety threats such as xenotropic murine leukemia virus-related virus. Blood safety studies have included protocols evaluating epidemiologic and/or laboratory aspects of human immunodeficiency virus, human T-lymphotropic virus 1/2, hepatitis C virus, hepatitis B virus, West Nile virus, cytomegalovirus, human herpesvirus 8, parvovirus B19, malaria, Creutzfeldt-Jakob disease, influenza, and Trypanosoma cruzi infections. Other analyses have characterized blood donor demographics, motivations to donate, factors influencing donor return, behavioral risk factors, donors' perception of the blood donation screening process, and aspects of donor deferral. In REDS-II, 2 large-scale blood donor protocols examined iron deficiency in donors and the prevalence of leukocyte antibodies. This review describes the major study results from over 150 peer-reviewed articles published by these 2 REDS programs. In 2011, a new 7-year program, the Recipient Epidemiology and Donor Evaluation Study-III, was launched. The Recipient Epidemiology and Donor Evaluation Study-III expands beyond donor-based research to include studies of blood transfusion recipients in the hospital setting and adds a third country, South Africa, to the international program.

Anti-Trypanosoma cruzi inconclusive results in blood donor screening

The common occurrence of inconclusive results in blood donor screening for anti-Trypanosoma cruzi antibodies should be interpreted with caution. It is important to consider the fact that blood transfusion services in Brazil and some other Latin America countries simultaneously perform two tests that use different methodologies to detect anti-T. cruzi antibodies; this is determined by legislation currently in force in Brazil (Resolution 721 of August 9, 1989, and Resolution 1376 of November 19, 1993)(1-3). This issue of the Journal Brasileira de Hematologia e Hemoterapia includes a study from the Blood Bank in Uberaba that employed three tests: enzyme immunoassay (EIA), indirect hemagglutination and indirect immunofluorescence(4). Samples that presented discordantresults between tests were considered inconclusive, for example: positive in one or two tests and negative in the other(s) and for samples with optical density/cut-off limit (OD/CO) values of 0.8 to 1.2 (the gray zone) in the ELISA test. The high rates of inconclusive results reported are mostly a result of the sum of false results of the three tests. The diagnosis of Chagas disease is usually performed by the detection of anti-T. cruzi antibodies. Since Guerreiro and Machado developed the complement fixation method in 1913, the sensitivity and specificity of these tests have improved considerably(5). The first Brazilian legislation that mentioned serology screening for Chagas disease is a decree dated September 25, 1969, of the Comissao Nacional de Hemoterapia, that states in no 4, that serological screening for Chagas disease should be made prior to or subsequent to each donation and,when positive, the donor should be excluded and any collected blood discarded(6). The first generation of commercially available serological anti-T. cruzi tests employed purified or total antigenic fractions of the epimastigote form of T. cruzi with the high rate offalse positive as well as false negative results being unwanted characteristics of these tests. So,Decrees 721 of August 9, 1989 and 1376 of November 19, 1993 stipulate that serology screeningfor Chagas disease should be performed using two methods that apply different principles(1-3). With the advent of sequencing and cloning immunodominant antigens of T. cruzi came the development of tests using recombinant protein mixtures of the parasite and/or synthetic peptides which resulted in an increase in the sensitivity and specificity. Moreover, it was only with Resolution 343 of December 13, 2002, that highly sensitive blood donor screening for Chagas disease using an enzyme immunoassay (EIA) test was established as compulsory. At the same time, the blood transfusion services gradually implemented a set of quality control measures and introduced computer systems, which together, gradually reduced the number of erroneous and inconclusive results. In this study by Pereira et al.(4), the prevalence found in the group of inconclusive samples was 13.3%; Remesar et al.(7) reported a prevalence of 18% in Chaco province, Argentina, where the prevalence of the disease is high (24.5%), Otani et al.(8) found 17% in samplescollected from ten Latin America countries and Sabino et al. reported a prevalence of 20% for Brazil in the International Retrovirus Epidemiology Donor Study-II (REDS-II)(9). An understanding of the meaning of results with low reactivity in screening tests to detect anti- T. cruzi antibodies however has not been reached. Sabino et al. (in press) report that the drop in the S/CO index in ten patients with negative results for Chagas disease using a polymerase chain reactiontechnique may be an indication of seroreversion as a result of a spontaneous cure of the disease. The current work shows that the interpretation of the results of serology screening for anti- T. cruzi in association with the epidemiological data is strategically important for blood safety and for the diagnosis of Chagas disease(4).

Human immunodeficiency virus prevalence, incidence, and residual risk of transmission by transfusions at Retrovirus Epidemiology Donor Study-II blood centers in Brazil.

In Brazil nationally representative donor data are limited on human immunodeficiency virus (HIV) prevalence, incidence, and residual transfusion risk. The objective of this study was to analyze HIV data obtained over 24 months by the Retrovirus Epidemiology Donor Study-II program in Brazil. Donations reactive to third- and fourth-generation immunoassays (IAs) were further confirmed by a less-sensitive (LS) IA algorithm and Western blot (WB). Incidence was calculated for first-time (FT) donors using the LS-EIA results and for repeat donors with a model developed to include all donors with a previous negative donation. Residual risk was projected by multiplying composite FT and repeat donor incidence rates by HIV marker-negative infectious window periods. HIV prevalence among FT donors was 92.2/10(5) donations. FT and repeat donor and composite incidences were 38.5 (95% confidence interval [CI], 25.6-51.4), 22.5 (95% CI, 17.6-28.0), and 27.5 (95% CI, 22.0-33.0) per 100,000 person-years, respectively. Male and community donors had higher prevalence and incidence rates than female and replacement donors. The estimated residual risk of HIV transfusion transmission was 11.3 per 10(6) donations (95% CI, 8.4-14.2), which could be reduced to 4.2 per 10(6) donations (95% CI, 3.2-5.2) by use of individual-donation nucleic acid testing (NAT). The incidence and residual transfusion risk of HIV infection are relatively high in Brazil. Implementation of NAT will not be sufficient to decrease transmission rates to levels seen in the United States or Europe; therefore, other measures focused on decreasing donations by at-risk individuals are also necessary.

Donation return time at fixed and mobile donation sites

This study investigated the effect of blood donation environment, fixed or mobile with differing sponsor types, on donation return time. Data from 2006 through 2009 at six US blood centers participating in the Retrovirus Epidemiology Donor Study-II (REDS-II) were used for analysis. Descriptive statistics stratified by whole blood (WB), plateletpheresis (PP), and double red blood cell (R2) donations were obtained for fixed and mobile locations, including median number of donations and median interdonation interval. A survival analysis estimated median return time at fixed and mobile sites, while controlling for censored return times, demographics, blood center, and mandatory recovery times. Two-thirds (67.9%) of WB donations were made at mobile sites, 97.4% of PP donations were made at fixed sites, and R2 donations were equally distributed between fixed and mobile locations. For donations at fixed sites only or alternating between fixed and mobile sites, the highest median numbers of donations were nine and eight, respectively, and the shortest model-adjusted median return times (controlling for mandatory eligibility times of 56 and 112 days) were 36 and 30 days for WB and R2 donations, respectively. For PP donations, the shortest model-adjusted median return time was 23 days at a fixed location and the longest was 693 days at community locations. WB, PP, and R2 donors with the shortest time between donations were associated with fixed locations and those alternating between fixed and mobile locations, even after controlling for differing mandatory recovery times for the different blood donation procedures.

Iron deficiency in whole blood donors

Each year, 5 million regular donors meet almost half the transfusion needs of the United States by voluntarily giving their blood. In this issue of Transfusion, we learn how well the needs of these committed donors are being met from an analysis of enrollment data from the Retrovirus Epidemiology Donor Study-II (REDS-II) Donor Iron Status Evaluation (RISE) study of the National Heart, Lung, and Blood Institute.1 The RISE study is the largest and most comprehensive study yet conducted of iron deficiency in blood donors, with an enrollment of 2,425 women and men. The results are alarming. Among frequent donors, two-thirds (66%) of the women and almost half (49%) of the men were iron deficient.1 The true prevalence of iron deficiency among regular donors is surely higher; the RISE study enrolled only frequent donors who had been accepted for donation, excluding those deferred for a low hemoglobin concentration. Moreover, the enrolled, iron-deficient donors then each donated a unit of whole blood, further depleting their body iron by an additional 200 to 250 mg. Neither these loyal donors nor the national blood supply are well served by the collection practices and regulatory framework that have produced widespread iron deficiency among those who regularly give their blood.

Donation frequency of blood donors participating in a prospective cohort study of iron status

Blood centers are interested in understanding determinants of frequent blood donation. We hypothesized that participation in uncompensated research could result in higher donation rates. Donation rates for 2425 subjects from six US blood centers enrolled in the Retrovirus Epidemiology Donor Study-II Donor Iron Status Evaluation Study were compared to those of nonenrolled donors (n = 202,383). Over 15 months, we compared mean donation rates and adjusted rate ratios (RRs) between enrolled and nonenrolled for three subgroups, first-time, reactivated, and frequent donors, and donation rates before and after the study enrollment period for frequent donors only. Enrolled donors had higher 15-month mean donation rates than nonenrolled donors (first-time, 1.21 [RR = 1.91]; reactivated, 1.68 [RR = 1.83]; frequent, 3.40 [RR = 1.12]). However, frequent donors donated at approximately the same rate after enrollment as they did before enrollment in the study (3.62 per 15 months [RR = 1.12]). Donors enrolled in the study donated at a higher rate than nonenrolled donors, but frequent donors remained consistent in their donation frequency both before and after enrollment. Although increased donation rates could have been causally related to study enrollment, we cannot rule out an enrollment bias whereby more committed donors were more likely to enroll in the study.

Transfusion recipient epidemiology and outcomes research: possibilities for the future

The National Heart, Lung, and Blood Institute (NHLBI) supports major research programs related to the field of transfusion medicine, which encompass blood banking, the practice of transfusion medicine itself, and cellular therapies. Specific programmatic elements have included 1) the Transfusion Medicine/Hemostasis Clinical Trials Network (TMH CTN) charged with conducting clinical trials in transfusion medicine and hemostasis; 2) the Retrovirus Epidemiology Donor Study-II (REDS-II), which includes domestic and international efforts dedicated to blood donor safety and blood availability issues; 3) the Specialized Centers of Clinically Oriented Research (SCCOR) in Transfusion Biology and Medicine that include two major projects, the Biologic and Immunologic Aspects of Transfusion Medicine Program and the Transfusion and Lung Injury Program, and 4) the Transfusion Therapy Trial for Functional Outcomes in Cardiovascular Patients Undergoing Surgical Hip Fracture Repair (FOCUS), a Phase III clinical trial that has as its major goal to determine whether a more aggressive transfusion strategy in surgery patients with cardiovascular disease (or risk factors) is associated with improved functional recovery and decreased risk of adverse postoperative outcomes. Notably, none of these programs supports epidemiologic and clinical outcomes research focused on transfusion recipients. Thus, on October 31, 2007, a Working Group on Transfusion Recipient Epidemiology and Outcomes Research was convened by the NHLBI. This group was asked to discuss the current status of the field, identify critical research needs, and make recommendations to the NHLBI program staff.

Influenza viremia and the potential for blood‐borne transmission

I nfluenza is a major cause of morbidity and mortality in the United States and worldwide. The threat of pandemic influenza recently has gained prominent attention because of widespread infection of poultry with highly pathogenic avian influenza A (H5N1) and the potential for the virus to mutate into one capable of efficient human-to-human transmission. As of March 8, 2007, 277 human cases of H5N1 infection had been reported to WHO from Asia, Eastern Europe, and Africa, mostly as a result of close contact between humans and infected birds, although rare, unsustained human-to-human transmission has been documented. If a change in viral characteristics were to allow efficient human-to-human transmission, rapid spread and a worldwide pandemic could result. The global spread of H5N1, continuing outbreaks in birds, and sporadic infections in humans have increased concern that a pandemic virus may emerge and cause an influenza pandemic. The possibility of an influenza pandemic has focused attention on the epidemiology and pathophysiology of influenza, including its potential for transmission through the blood supply. An infectious agent which has a blood-borne phase and can be clinically asymptomatic has the potential to be transmitted by blood transfusion. Planning to ensure an adequate and safe national blood supply during a pandemic prompted consideration of the potential for transfusion-transmitted influenza. Notably, no cases of transfusion transmission of influenza have been documented to date. The risk of transfusion transmission has been assumed to be negligible based on the premise that viremia rarely occurs and does not occur without symptoms, allowing for deferral of potentially infectious blood donors. If these assumptions are incorrect, however, and influenza infection commonly involves a viremic phase, especially before the onset of symptoms, and if influenzainfected blood resulted in clinical illness, it would have implications for blood safety. To further examine this possibility, we surveyed the literature underlying these assumptions and propose methods of redressing gaps in our knowledge. If influenza were transmissible by transfusion, blood product recipients, who include a high proportion of immunocompromised patients, might suffer increased morbidity and mortality. In bone marrow transplant populations influenza infection appears to be associated with approximately 25 percent mortality. If influenza were deemed to represent a transfusion transmission risk, possible screening methods would likely rely on epidemiologic query or laboratory screening. With any screening there is a risk of impacting supply. Testing of the blood supply would also become particularly important if a pandemic were to be caused by a virus similar to the highly pathogenic influenza A (H5N1). Infection in humans has thus far resulted in approximately 60 percent case fatality ratio where the virus has been isolated outside of the respiratory tract, a factor not typically seen with seasonal influenza infections. Detection of influenza in the blood of H5N1 infected humans and in animal studies has occurred predominantly during symptomatic periods and at high viral titers. A positive test might result in discarding ABBREVIATION: CSF = cerebrospinal fluid.

A perspective on transfusion‐related acute lung injury two years after the Canadian Consensus Conference

A perspective on transfusion‐related acute lung injury two years after the Canadian Consensus Conference