Transfusion-transmissible coinfections among US blood donors.

BACKGROUND: Transfusion-transmissible infection (TTI) prevalence among US blood donors has been widely documented. Here we estimate the prevalence of donors presenting with ≥2 TTIs (multiple infections past or present referred to as coinfections) and describe their demographics and associations. METHODS: Data from the Transfusion-Transmissible Infections Monitoring System were compiled for October 2020-September 2023 (3 years). Prevalence per million donations (pmd) was calculated for each TTI coinfection combination with demographic characteristics summarized. The odds of each TTI coinfection combination were estimated using logistic regression. Reactivity by NAT and/or serology (HIV, HBV, and HCV) defined donors as consensus positive (CP) for each infection while serology-based algorithms defined syphilis CP and the subset with active syphilis infections (ASIs). RESULTS: About 22 million donations were included, with 212 coinfections (9.7 pmd). Around 2% of donations positive for any TTI (n = 10,516) were coinfections. Coinfection prevalence per TTI combination ranged from 0.3 pmd for HIV CP and HCV CP, to 4.3 pmd for HIV CP and syphilis CP. There were high proportions of coinfections from donors who were male, aged 25-54 years, white or black, first time, and residing in the southern US Census Region. The odds of a second TTI occurring in an individual donor with a TTI ranged from 23 (95% CI: 13, 41) times more likely for HBV CP and ASI to 395 (95% CI: 298, 524) times more likely for HIV CP and ASI. CONCLUSIONS: Coinfections are relatively uncommon among blood donors in the United States; however, associations exist among HIV, HBV, HCV, and syphilis infections.

Modeling US blood donor deferrals under a policy of individual risk assessment for HIV risk sexual behavior.

BACKGROUND: In May 2023, the Food and Drug Administration (FDA) released final guidance for blood donor eligibility that recommended the elimination of 3-month deferral for men who have sex with men (MSM) and the related deferral for women who have sex with MSM. In its place, FDA introduced an individual risk assessment policy of asking all presenting blood donors, regardless of sex or gender, if they have had a new partner or more than one sexual partner in the last 3 months and deferring those who also report anal sex (penile-anal intercourse) during this period. We modeled the possible impact of this policy on the US blood donor base. STUDY DESIGN AND METHODS: We developed a computational model to estimate the percentage of blood donors who would be deferred under a policy of individual HIV risk assessment. The model incorporated demographic information about donors and national survey data on HIV risk behaviors and included age and sex distributions and dependencies. RESULTS: Our model estimates that approximately 1.2% of US blood donors would be deferred under the individual HIV risk assessment paradigm. DISCUSSION: The model predicts a relatively minor effect of replacing the time-based deferral for MSM with individual risk-based deferral for sexual behavior. As US blood centers implement this new policy, the effect may be mitigated by donor gains, which warrant further study. The new policy is unlikely to adversely affect the availability of blood and blood components.

Changes in transfusion-transmissible infection prevalence and demographics among US blood donors during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic impacted the US blood supply. We compared blood donor demography and infectious disease prevalence before and during the pandemic using a large multicenter database. METHODS: Data were categorized as "Before COVID-19" (March 2018-February 2020) or "During COVID-19" (March 2020-February 2022). Donor demographics, donation frequency, and infectious marker prevalence of HIV, HBV, and HCV were compared for the two time periods. The odds of a donor testing positive for these infections among the two time periods were calculated using multivariable logistic regression. RESULTS: Our study assessed a total of 26,672,213 donations including 13,430,380 before and 13,241,833 during COVID-19. There were significantly more donations from donors who were female, aged 40 and older, white, and repeat, during COVID-19. Donation frequency comparison quantified the increase in donations from donors who were white, female, older, and repeat during the pandemic. The prevalence of HIV and HCV decreased significantly during COVID-19 compared to before, but not for HBV. For HIV, the adjusted odds of infection during the pandemic did not differ but for HBV, the odds were significantly more likely during the pandemic and were significantly lower for HCV. DISCUSSION: Demographics and infectious disease marker prevalence changed during the COVID-19 pandemic in the United States. Prevalence of each infection in the donor population will continue to be monitored to determine if changes were specific to the pandemic period.

Haemovigilance resources available for everyone: A report from the International Haemovigilance Tools Collaborative Project.

BACKGROUND AND OBJECTIVES: Haemovigilance systems are intended to collect and analyse data, and report findings relating to transfusion complications, such as blood product safety, procedural incidents, and adverse reactions in donors and patients. A common problem among developing haemovigilance programs is the lack of resources and tools available to countries striving to establish or enhance their haemovigilance system. MATERIALS AND METHODS: World Health Organization, in collaboration with International Society for Blood Transfusion (ISBT), International Haemovigilance Network and other haemovigilance experts embarked on a Haemovigilance Tools Project to collect and provide materials and resources to assist with the stepwise implementation of haemovigilance. RESULTS AND CONCLUSIONS: Resources are housed as a virtual compendium on the ISBT website under the Haemovigilance Working Party. These are managed by a subcommittee of the Working Party and are freely available and downloadable to all without requiring ISBT membership.

HIV risk behavior profiles among men who have sex with men interested in donating blood: Findings from the Assessing Donor Variability and New Concepts in Eligibility study.

BACKGROUND: Individual risk assessment allows donors to be evaluated based on their own behaviors. Study objectives were to assess human immunodeficiency virus (HIV) risk behaviors in men who have sex with men (MSM) and estimate the proportion of the study population who would not be deferred for higher risk HIV sexual behaviors. STUDY DESIGN AND METHODS: Cross-sectional survey and biomarker assessment were conducted in eight U.S. cities. Participants were sexually active MSM interested in blood donation aged 18-39 years, assigned male sex at birth. Participants completed surveys during two study visits to define eligibility, and self-reported sexual and HIV prevention behaviors. Blood was drawn at study visit 1 and tested for HIV and the presence of tenofovir, one of the drugs in oral HIV pre-exposure prophylaxis (PrEP). Associations were assessed between HIV infection status or HIV PrEP use and behaviors, including sex partners, new partners, and anal sex. RESULTS: A total of 1566 MSM completed the visit 1 questionnaire and blood draw and 1197 completed the visit 2 questionnaire. Among 1562 persons without HIV, 789 (50.4%) were not taking PrEP. Of those not taking PrEP, 66.2% reported one sexual partner or no anal sex and 69% reported no new sexual partners or no anal sex with a new partner in the past 3 months. CONCLUSION: The study found that questions were able to identify sexually active, HIV-negative MSM who report lower risk sexual behaviors. About a quarter of enrolled study participants would be potentially eligible blood donors using individual risk assessment questions.

Early administration of COVID-19 convalescent plasma with high titer antibody content by live viral neutralization assay is associated with modest clinical efficacy.

The efficacy of COVID-19 convalescent plasma (CCP) as a treatment for hospitalized patients with COVID-19 remains somewhat controversial; however, many studies have not evaluated CCP documented to have high neutralizing antibody titer by a highly accurate assay. To evaluate the correlation of the administration of CCP with titer determined by a live viral neutralization assay with 7- and 28-day death rates during hospitalization, a total of 23 118 patients receiving a single unit of CCP were stratified into two groups: those receiving high titer CCP (>250 50% inhibitory dilution, ID50; n = 13 636) or low titer CCP (≤250 ID50; n = 9482). Multivariable Cox regression was performed to assess risk factors. Non-intubated patients who were transfused with high titer CCP showed 1.1% and 1.7% absolute reductions in overall 7- and 28-day death rates, respectively, compared to those non-intubated patients receiving low titer CCP. No benefit of CCP was observed in intubated patients. The relative benefit of high titer CCP was confirmed in multivariable Cox regression. Administration of CCP with high titer antibody content determined by live viral neutralization assay to non-intubated patients is associated with modest clinical efficacy. Although shown to be only of modest clinical benefit, CCP may play a role in the future should viral variants develop that are not neutralized by other available therapeutics.

Neonatal and pediatric blood bank practice in the United States: Results from the AABB pediatric transfusion medicine subsection survey.

BACKGROUND: There are limited standards guiding the selection and processing of blood components specific for neonatal and pediatric transfusions. Therefore, blood banks (BBs) and transfusion services must create their own policies and procedures. STUDY DESIGN AND METHODS: The American Association of Blood Banks (AABB) Pediatric Transfusion Medicine Subsection Committee developed a 74-question survey to capture neonatal and pediatric BB practices in the United States. RESULTS: Thirty-five centers completed the survey: a response rate 15.8%. Responses indicated that most carry a mixed inventory of red blood cells (RBCs); 94.2% allow more than one type of RBC product for small-volume (SV) and large-volume (LV) transfusions to neonatal and pediatric patients. Many had storage age thresholds for RBCs transfused to neonates (SV = 60%, LV = 67.7%) but not older pediatric patients. The use of Group O for nonurgent RBC transfusion in neonates was common (74.2%). Responses related to special processing of RBCs and platelets indicated that 100% RBC and platelets are leukocyte-reduced (LR) for neonates and 97% for non-neonates. Irradiation of RBCs and platelets was commonly performed for neonatal transfusion (88.6%). Providing cytomegalovirus (CMV) seronegative products, volume reduction, and washing were variable. All centers transfused single-donor apheresis platelets; 20% allowed pathogen reduction (PR). The majority of centers have strategies limiting the amount of incompatible plasma transfused; however, few titrate ABO isoagglutinins in plasma-containing products (20% for platelets and 9.1% for plasma). CONCLUSIONS: Variability exists in BB practice for neonatal and pediatric transfusion. Future studies are needed to understand and define best BB practices in these patient populations.

Use of a rapid electronic survey methodology to estimate blood donors' potential exposure to emerging infectious diseases: Application of a statistically representative sampling methodology to assess risk in US blood centers.

Risk assessments of transfusion-transmitted emerging infectious diseases (EIDs) are complicated by the fact that blood donors' demographics and behaviors can be different from the general population. Therefore, when assessing potential blood donor exposure to EIDs, the use of general population characteristics, such as U.S. travel statistics, may invoke uncertainties that result in inaccurate estimates of blood donor exposure. This may, in turn, lead to the creation of donor deferral policies that do not match actual risk. STUDY DESIGN AND METHODS: This article reports on the development of a system to rapidly assess EID risks for a nationally representative portion of the U.S. blood donor population. To assess the effectiveness of this system, a test survey was developed and deployed to a statistically representative sample frame of blood donors from five blood collecting organizations. Donors were directed to an online survey to ascertain their recent travel and potential exposure to Middle East respiratory syndrome coronavirus (MERS-CoV). RESULTS: A total of 7128 responses were received from 54 256 invitations. The age-adjusted estimated total number of blood donors potentially exposed to MERS-CoV was approximately 15 640 blood donors compared to a lower U.S. general population-based estimate of 9610 blood donors. CONCLUSION: The structured donor demographic sample-based data provided an assessment of blood donors' potential exposure to an emerging pathogen that was 63% larger than the U.S. population-based estimate. This illustrates the need for tailored blood donor-based EID risk assessments that provide more specific demographic risk intelligence and can inform appropriate regulatory decision making.

Safety incident reports associated with blood transfusions.

BACKGROUND: Patient safety remains a critical issue in health care. Adverse events related to blood transfusion constitute a threat to patient safety. The aim of this study is to compare and contrast reporting trends of patient safety events that occur during the transfusion of blood components in pediatric and adult hospital care settings. STUDY DESIGN AND METHODS: This is a multicenter analysis of reported patient safety incidents occurring during the administration of blood components for four children's and 21 adult hospitals from January 2010 through September 2017. Denominators were pediatric or adult transfusions per year for a subset of two pediatric and two adult hospitals able to provide denominators for the complete reporting period. Rates were calculated on the subset of four hospitals per 100,000 components transfused with Pearson's chi square for comparison (p < 0.05 as significant). RESULTS: There were 1902 reports for an estimated 1.1 million transfusions: 358 reports from pediatric hospitals and 1544 reports from adult hospitals. From hospitals able to provide denominator data; there were 192 reports for 128,560 pediatric transfusions and 183 reports for 377,563 adult transfusions. The reporting rate per 100,000 components from these four hospitals was 149 for pediatric and 48 for adult reports (p < 0.01). CONCLUSION: This analysis demonstrates the continued need for transfusion safety practices. The type of incident reports differed in the pediatric setting compared to the adult setting. Understanding patient safety event reporting trends related to blood transfusion will help target hemovigilance education and interventions to the appropriate patient populations.

Analysis of pediatric adverse reactions to transfusions.

BACKGROUND: Children are known to be physiologically and biochemically different from adults. However, there are no multi-institutional studies examining the differences in the frequency, type, and severity of transfusion reactions in pediatric versus adult patients. This study aims to characterize differences between pediatric and adult patients regarding adverse responses to transfusions. STUDY DESIGN AND METHODS: This is a retrospective data analysis of nine children's hospitals and 35 adult hospitals from January 2009 through December 2015. Included were pediatric and adult patients who had a reported reaction to transfusion of any blood component. Rates are reported as per 100,000 transfusions for comparison between pediatric and adult patients. RESULTS: Pediatric patients had an overall higher reaction rate compared to adults: 538 versus 252 per 100,000 transfusions, notably higher for red blood cell (577 vs. 278 per 100,000; p < 0.001) and platelet (833 vs. 358 per 100,000; p < 0.001) transfusions. Statistically higher rates of allergic reactions, febrile nonhemolytic reactions, and acute hemolytic reactions were observed in pediatric patients. Adults had a higher rate of delayed serologic transfusion reactions, delayed hemolytic transfusion reactions, and transfusion-associated circulatory overload. CONCLUSION: Pediatric patients had double the rate of transfusion reactions compared to adults. The nationally reported data on reaction rates are consistent with this study's findings in adults but much lower than the observed rates for pediatric patients. Future studies are needed to address the differences in reaction rates, particularly in allergic and febrile reactions, and to further address blood transfusion practices in the pediatric patient population.

Impact of changes to donor hemoglobin criteria on the rate of donor deferral.

BACKGROUND: The Food and Drug Administration's requirements for "Blood and Blood Components Intended for Transfusion or Further Manufacturing Use" (Final Rule) effective May 2016 changed eligibility criteria for blood donors. A multivariate analysis was performed to measure its impact on donor deferral rates. STUDY DESIGN AND METHODS: Four blood centers submitted data for similar 6-month periods before and after implementation of the Final Rule. Data included presenting donors, units collected, deferrals, intended products from deferred donors, deferral reasons, presenting donor demographics, donor hemoglobin (Hgb), hematocrit (HCT), pulse, blood pressure (BP), temperature, and other reasons for deferral. Data were aggregated and periods compared. RESULTS: After Final Rule implementation, successful donations decreased by 1.3% (83.1%-81.9%), despite a 0.2% increase in presenting donors. The rate of Hgb/HCT, pulse, and deferrals increased, while deferrals for other reasons decreased. Male Hgb/HCT deferral rates increased 1.2% (4213 total). Black male donors' Hgb/HCT deferral rate increased (2.7%-5.2%) but was counterbalanced by an overall 3.7% decrease in black female Hgb/HCT deferrals. While Hgb/HCT deferrals of black donors remained stable overall (17.0% vs. 16.2%), this trend was not observed by all centers. Deferrals for pulse increased (0.2%), as did BP deferrals (0.2%). CONCLUSION: Although there was a small increase in presenting donors after implementation of the Final Rule, there was a decrease in successful donations. While it appeared that deferral in black donors was unchanged, this trend was not observed across all centers. Pulse and BP deferrals rose dissimilarly among centers, according to individual procedures.

International validation of harmonized definitions for complications of blood donations.

BACKGROUND: In December 2014, a multinational collaboration of hemovigilance experts from the International Society of Blood Transfusion (ISBT), the International Hemovigilance Network, and AABB published harmonized definitions of complications related to blood donation titled "Standard for Surveillance of Complications Related to Blood Donation." Both mandatory and optional terms were included. The definitions are endorsed by the Alliance of Blood Operators and the European Blood Alliance. STUDY DESIGN AND METHODS: The objective of this study was to validate harmonized donor hemovigilance definitions with potential users. In June 2016, 30 real-world cases were sent to potential users around the world along with the definitions, an answer sheet, and instructions on how to complete the validation exercise. RESULTS: Overall, 54 responses from 25 countries were received, including over 400 comments. The results were presented for feedback at both ISBT and AABB meetings. Case diagnoses were consistent across most responders. Exceptions were rare adverse events, nonstandard presentations, or incomplete information. In general, the application of optional definitions, including severity grading and imputability, had the most variability. CONCLUSION: The use of standardized terms in the donor setting serves to increase focus on donor safety, facilitate conversation, foster exchange of information, and frame questions for future research. Overall, the definitions provide adequate coverage of donor reactions; however, some terms require clarification. Severity grading and imputability and other optional terms need clear and objective definitions and instructions on when and how to use them. Additional feedback and final recommendations are summarized in this report.

A brief overview of clinical significance of blood group antibodies.

CONCLUSIONS: This review was derived from a presentation made on September 2, 2016 for the first Academy Day presented by the Working Party on Immunohematology at the International Society of Blood Transfusion (ISBT) Congress in Dubai. The focus of this review is to provide a brief overview of the clinical significance of blood group antibodies. Blood group antibodies can be naturally occurring (e.g., anti-A and anti-B through exposure to naturally occurring red blood cell [RBC] antigen-like substances) or can occur via exposure to foreign (donor) RBC antigens through previous transfusions, transplants, or exposure to fetal RBCs during or after pregnancy. However, not all blood group antibodies are clinically significant. Clinically significant blood group antibodies can cause adverse events after blood component transfusion or transplantation and/or can cause hemolytic disease of the fetus and newborn.

Hemovigilance and the Notify Library.

CONCLUSIONS: Hemovigilance systems allow reporting of adverse occurrences associated with blood transfusion to a central database where events can be reviewed and analyzed for the benefit of patients and donors. Hemolytic and serologic transfusion reactions are among the many types of reactions reported to these systems. The Notify Library, a database of adverse events associated with medical products of human origin, has incorporated hemovigilance into its didactic resources. Students and practitioners are encouraged to use the electronic library and to further enhance this resource through review and recommendation of additional publications in the area of immunohematology.

Changes in hospital human tissue oversight in the United States between 2005 and 2011: results of a follow-up AABB survey.

BACKGROUND: In 2005, The Joint Commission (TJC) implemented tissue storage and issuance standards for hospital oversight, which AABB assessed by survey. This follow-up survey of AABB's membership, 6 years later, ascertained changes after TJC implementation of tissue standards. STUDY DESIGN AND METHODS: AABB's Biovigilance Tissue Working Group conducted a Web-based survey, distributed to 1069 hospital institutional members in June 2011. Human tissue types used, departmental responsibilities, and views of AABB involvement were queried. RESULTS: Of the 336 (31%) total respondents, 84% use allogeneic and/or autologous human tissue. Sixty-one percent have stored tissue on consignment. As in 2005, the department of surgery most often had responsibility for tissue use, followed by the blood bank or transfusion service (BBTS). Overall, the BBTS had a smaller role in oversight of autologous tissue acquisition in 2011 versus 2005, but no change in level of responsibility for storage or issue of tissues. Hospitals reported the BBTS and combined blood and tissue services (CBTS) added responsibilities for storing and monitoring eye tissue and heart valves (p < 0.05) since 2005. The BBTS/CBTS increased their degree of responsibility for reporting suspected postimplant infection and other adverse reactions for musculoskeletal allografts (p < 0.01), eye tissue (p < 0.005), and eye tissue recipients recall notification (p < 0.05). The BBTS/CBTS have more responsibility than any other department for stem cell and cord blood management. CONCLUSIONS: In this survey, AABB institutional members reported that BBTS are more involved than previously in the regulatory aspects of human tissue oversight and remain involved in many operational aspects of hospital tissue management.

How we forecast tomorrow's haemovigilance.

The field of haemovigilance continues to develop, building on more than forty years of international experience. This review considers the current scope and activities of haemovigilance around the world and explores aspects of preparation for the advent of new blood products and alternative therapies to transfusion; new tools for data acquisition (including patient- and donor-reported outcomes, and data from 'wearables') and the analysis and communication of haemovigilance results.

Modeling the Risk of HIV Transfusion Transmission.

BACKGROUND: Blood donations are routinely screened for HIV to prevent an infectious unit from being released to the blood supply. Despite improvements to blood screening assays, donations from infected donors remain undetectable during the window period (WP), when the virus has not yet replicated above the lower limit of detection (LOD) of a screening assay. To aid in the quantitative risk assessments of WP donations, a dose-response model describing the probability of transfusion-transmission of HIV over a range of viral RNA copies was developed. METHODS: An exponential model was chosen based on data fit and parsimony. A data set from a HIV challenge study using a nonhuman primate model and another data set from reported human blood transfusions associated with HIV infected donors were separately fit to the model to generate parameter estimates. A Bayesian framework using No-U-Turn Sampling (NUTS) and Monte Carlo simulations was performed to generate posterior distributions quantifying uncertainty in parameter estimation and model predictions. RESULTS: The parameters of the exponential model for both nonhuman primate and human data were estimated with a mean (95% credible intervals) of 2.70 × 10 -2 (7.74 × 10 -3 , 6.06 × 10 -2 ) and 7.56 × 10 -4 (3.68 × 10 -4 , 1.31 × 10 -3 ), respectively. The predicted ID 50 for the animal and human models was 26 (12, 90) and 918 (529, 1886) RNA copies transfused, respectively. CONCLUSION: This dose-response model can be used in a quantitative framework to estimate the probability of transfusion-transmission of HIV through WP donations. These models can be especially informative when assessing risk from blood components with low viral load.