Establishment of human post-vaccination SARS-CoV-2 standard reference sera.

There is a critical need to understand the effectiveness of serum elicited by different SARS-CoV-2 vaccines against SARS-CoV-2 variants. We describe the generation of reference reagents comprised of post-vaccination sera from recipients of different primary vaccines with or without different vaccine booster regimens in order to allow standardized characterization of SARS-CoV-2 neutralization in vitro. We prepared and pooled serum obtained from donors who received a either primary vaccine series alone, or a vaccination strategy that included primary and boosted immunization using available SARS-CoV-2 mRNA vaccines (BNT162b2, Pfizer and mRNA-1273, Moderna), replication-incompetent adenovirus type 26 vaccine (Ad26.COV2·S, Johnson and Johnson), or recombinant baculovirus-expressed spike protein in a nanoparticle vaccine plus Matrix-M adjuvant (NVX-CoV2373, Novavax). No subjects had a history of clinical SARS-CoV-2 infection, and sera were screened with confirmation that there were no nucleocapsid antibodies detected to suggest natural infection. Twice frozen sera were aliquoted, and serum antibodies were characterized for SARS-CoV-2 spike protein binding (estimated WHO antibody binding units/ml), spike protein competition for ACE-2 binding, and SARS-CoV-2 spike protein pseudotyped lentivirus transduction. These reagents are available for distribution to the research community (BEI Resources), and should allow the direct comparison of antibody neutralization results between different laboratories. Further, these sera are an important tool to evaluate the functional neutralization activity of vaccine-induced antibodies against emerging SARS-CoV-2 variants of concern. IMPORTANCE: The explosion of COVID-19 demonstrated how novel coronaviruses can rapidly spread and evolve following introduction into human hosts. The extent of vaccine- and infection-induced protection against infection and disease severity is reduced over time due to the fall in concentration, and due to emerging variants that have altered antibody binding regions on the viral envelope spike protein. Here, we pooled sera obtained from individuals who were immunized with different SARS-CoV-2 vaccines and who did not have clinical or serologic evidence of prior infection. The sera pools were characterized for direct spike protein binding, blockade of virus-receptor binding, and neutralization of spike protein pseudotyped lentiviruses. These sera pools were aliquoted and are available to allow inter-laboratory comparison of results and to provide a tool to determine the effectiveness of prior vaccines in recognizing and neutralizing emerging variants of concern.

Leveraging Donor Populations to Study the Epidemiology and Pathogenesis of Transfusion-Transmitted and Emerging Infectious Diseases.

The tragedy of transfusion-associated hepatitis and HIV spurred a decades-long overhaul of the regulatory oversight and practice of blood transfusion. Consequent to improved donor selection, testing, process control, clinical transfusion practice and post-transfusion surveillance, transfusion in the United States and other high-income countries is now a very safe medical procedure. Nonetheless, pathogens continue to emerge and threaten the blood supply, highlighting the need for a proactive approach to blood transfusion safety. Blood donor populations and the global transfusion infrastructure are under-utilized resources for the study of infectious diseases. Blood donors are large, demographically diverse subsets of general populations for whom cross-sectional and longitudinal samples are readily accessible for serological and molecular testing. Blood donor collection networks span diverse geographies, including in low- and middle-income countries, where agents, especially zoonotic pathogens, are able to emerge and spread, given limited tools for recognition, surveillance and control. Routine laboratory storage and transportation, coupled with data capture, afford access to rich epidemiological data to assess the epidemiology and pathogenesis of established and emerging infections. Subsequent to the State of the Science in Transfusion Medicine symposium in 2022, our working group (WG), "Emerging Infections: Impact on Blood Science, the Blood Supply, Blood Safety, and Public Health" elected to focus on "leveraging donor populations to study the epidemiology and pathogenesis of transfusion-transmitted and emerging infectious diseases." The 5 landmark studies span (1) the implication of hepatitis C virus in post-transfusion hepatitis, (2) longitudinal evaluation of plasma donors with incident infections, thus informing the development of a widely used staging system for acute HIV infection, (3) explication of the dynamics of early West Nile Virus infection, (4) the deployment of combined molecular and serological donor screening for Babesia microti, to characterize its epidemiology and infectivity and facilitate routine donor screening, and (5) national serosurveillance for SARS-CoV-2 during the COVID-19 pandemic. The studies highlight the interplay between infectious diseases and transfusion medicine, including the imperative to ensure blood transfusion safety and the broader application of blood donor populations to the study of infectious diseases.

Proceedings of the 2022 NHLBI and OASH state of the science in transfusion medicine symposium.

BACKGROUND: State of the Science (SoS) meetings are used to define and highlight important unanswered scientific questions. The National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health, and the Office of the Assistant Secretary for Health (OASH), Department of Health and Human Services held a virtual SoS in transfusion medicine (TM) symposium. STUDY DESIGN AND METHODS: In advance of the symposium, six multidisciplinary working groups (WG) convened to define research priorities in the areas of: blood donors and the supply, optimizing transfusion outcomes for recipients, emerging infections, mechanistic aspects of components and transfusion, new computational methods in transfusion science, and impact of health disparities on donors and recipients. The overall objective was to identify key basic, translational, and clinical research questions that will help to increase and diversify the volunteer donor pool, ensure safe and effective transfusion strategies for recipients, and identify which blood products from which donors best meet the clinical needs of specific recipient populations. RESULTS: On August 29-30, 2022, over 400 researchers, clinicians, industry experts, government officials, community members, and patient advocates discussed the research priorities presented by each WG. Dialogue focused on the five highest priority research areas identified by each WG and included the rationale, proposed methodological approaches, feasibility, and barriers for success. DISCUSSION: This report summarizes the key ideas and research priorities identified during the NHLBI/OASH SoS in TM symposium. The report highlights major gaps in our current knowledge and provides a road map for TM research.

Demographics of first-time donors returning for donation during the pandemic: COVID-19 convalescent plasma versus standard blood product donors.

BACKGROUND: Previous studies have demonstrated low first-time donor return rates (DRR) following catastrophic events. Little is known, however, about the influence of demographic factors on the DRR of first-time donors during the COVID-19 pandemic, including the unique motivation of COVID-19 convalescent plasma (CCP) donors as compared to non-CCP donors. STUDY DESIGN AND METHODS: Thirteen blood collection organizations submitted deidentified data from first-time CCP and non-CCP donors returning for regular (non-CCP) donations during the pandemic. DRR was calculated as frequencies. Demographic factors associated with returning donors: race/ethnicity, gender, and generation (Gen Z: 19-24, Millennial: 25-40, Gen X: 41-56, and Boomer: ≥57 years old), within the CCP and non-CCP first-time cohorts were compared using chi-square test at p < .05 statistical significance. RESULTS: From March 2020 through December 2021, there were a total of 44,274 first-time CCP and 980,201 first-time non-CCP donors. DRR were 14.6% (range 11.9%-43.3%) and 46.6% (range 10.0%-76.9%) for CCP and non-CCP cohorts, respectively. Age over 40 years (Gen X and Boomers), female gender, and White race were each associated with higher return in both donor cohorts (p < .001). For the non-CCP return donor cohort, the Millennial and Boomers were comparable. CONCLUSION: The findings demonstrate differences in returning donor trends between the two donor cohorts. The motivation of a first-time CCP donor may be different than that of a non-CCP donor. Further study to improve first-time donor engagement would be worthwhile to expand the donor base with a focus on blood donor diversity emphasizing engagement of underrepresented minorities and younger donors.

Beyond COVID-19 and lessons learned in the United States.

The COVID-19 pandemic severely tested the resilience of the US blood supply with wild fluctuations in blood donation and utilisation rates as community donation opportunities ebbed and hospitals post-poned elective surgery. Key stakeholders in transfusion services, blood centres, supply chains and manufacturers reviewed their experiences during the SARS-CoV-2 pandemic as well as available literature to describe successes, opportunities for improvement and lessons learned. The blood community found itself in uncharted territory responding to restriction of its access to donors (approximately 20% decrease) and some supplies; environmental adjustments to address staff and donor concerns about coronavirus transmission; and the development of a new product (COVID-19 convalescent plasma [CCP]). In assuring that the needs of the patients were paramount, the donation process was safe, that clinicians had access to CCP, and vendor relationships aligned, the blood banking community relearned its primary focus: improving patient outcomes.

Access to and safety of COVID-19 convalescent plasma in the United States Expanded Access Program: A national registry study.

BACKGROUND: The United States (US) Expanded Access Program (EAP) to coronavirus disease 2019 (COVID-19) convalescent plasma was initiated in response to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. While randomized clinical trials were in various stages of development and enrollment, there was an urgent need for widespread access to potential therapeutic agents. The objective of this study is to report on the demographic, geographical, and chronological characteristics of patients in the EAP, and key safety metrics following transfusion of COVID-19 convalescent plasma. METHODS AND FINDINGS: Mayo Clinic served as the central institutional review board for all participating facilities, and any US physician could participate as a local physician-principal investigator. Eligible patients were hospitalized, were aged 18 years or older, and had-or were at risk of progression to-severe or life-threatening COVID-19; eligible patients were enrolled through the EAP central website. Blood collection facilities rapidly implemented programs to collect convalescent plasma for hospitalized patients with COVID-19. Demographic and clinical characteristics of all enrolled patients in the EAP were summarized. Temporal patterns in access to COVID-19 convalescent plasma were investigated by comparing daily and weekly changes in EAP enrollment in response to changes in infection rate at the state level. Geographical analyses on access to convalescent plasma included assessing EAP enrollment in all national hospital referral regions, as well as assessing enrollment in metropolitan areas and less populated areas that did not have access to COVID-19 clinical trials. From April 3 to August 23, 2020, 105,717 hospitalized patients with severe or life-threatening COVID-19 were enrolled in the EAP. The majority of patients were 60 years of age or older (57.8%), were male (58.4%), and had overweight or obesity (83.8%). There was substantial inclusion of minorities and underserved populations: 46.4% of patients were of a race other than white, and 37.2% of patients were of Hispanic ethnicity. Chronologically and geographically, increases in the number of both enrollments and transfusions in the EAP closely followed confirmed infections across all 50 states. Nearly all national hospital referral regions enrolled and transfused patients in the EAP, including both in metropolitan and in less populated areas. The incidence of serious adverse events was objectively low (<1%), and the overall crude 30-day mortality rate was 25.2% (95% CI, 25.0% to 25.5%). This registry study was limited by the observational and pragmatic study design that did not include a control or comparator group; thus, the data should not be used to infer definitive treatment effects. CONCLUSIONS: These results suggest that the EAP provided widespread access to COVID-19 convalescent plasma in all 50 states, including for underserved racial and ethnic minority populations. The study design of the EAP may serve as a model for future efforts when broad access to a treatment is needed in response to an emerging infectious disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT#: NCT04338360.

Powassan virus: What is the risk to the blood supply?

Powassan virus (POWV) is an emerging tick-borne arbovirus that is found widely in Canada, the Northeastern and Northcentral United States, and the Russian Far East. While still rare, there has been an increase in reported cases of POWV disease over the last decade; most (>90%) cases have been neuroinvasive and the associated fatality rate is high (>10%). Transfusion-associated risk of POWV remains uncertain; while no intervention is likely indicated, one probable case of transfusion-transmitted POWV in the context of an increase in the incidence of POWV and other tick-borne infections, merits vigilance.

Blood Product (Donor) Noninfectious and Infectious Testing and Modification.

Blood transfusion begins with safe donor selection and testing. In the United States, the blood supply and transfusion are highly regulated. Blood transfusion safety is multifaceted, whereby each of the elements of the blood safety value chain, spanning donor recruitment and qualification, to collection, blood processing, testing, transfusion practice, and posttransfusion surveillance, must be optimized to minimize risk. Pathogen inactivation is a promising approach to decrease bacterial contamination of platelets, inactivate parasites and viruses, and decrease risks associated with emerging and unidentified pathogens. This article offers an overview of blood donor infectious and noninfectious testing in the United States.

Blood transfusion trends in the United States: national inpatient sample, 2015 to 2018.

Blood transfusions are among the most common therapeutic procedures performed in hospitalized patients. This study evaluates contemporary national trends in red blood cell (RBC), plasma, platelet, and cryoprecipitate transfusions. National Inpatient Sample, the largest all-payer inpatient database representing 94% to 97% of the US population, was evaluated from the fourth quarter (Q4) of 2015 through 2018. Quarterly trends for the percentage of hospitalizations with a transfusion procedure were separately examined for each blood product using log binomial regression and reported as quarterly percent change (QPC). The percentage of hospitalizations with an RBC transfusion decreased from 4.22% (2015Q4) to 3.79% (2018Q4) (QPC = -0.72; 95% confidence interval [CI], -1.26 to -0.19; Ptrend = .008). Although plasma transfusions also decreased, QPC = -1.33 (95% CI, -2.00 to -0.65; Ptrend < .001), platelet transfusions remained stable QPC = -0.13 (95% CI, -0.99 to 0.73; Ptrend = .766). In contrast, hospitalizations with cryoprecipitate utilization significantly increased QPC = 2.01 (95% CI, 0.57 to 3.44; Ptrend = .006). Significant quarterly reductions in RBC transfusions were also seen among many, but not all, strata of sex, race/ethnicity, patient risk severity, and admission type (elective vs nonelective). Despite significant declines in RBC transfusions among older adults, there were no significant changes among pediatric age-group (<18 years) and those 18 to 49 years. The decline in RBC and plasma transfusions suggests steady incorporation of robust evidence base showing safety of restrictive transfusions. Increased cryoprecipitate use may be reflective of wider adoption of hypofibrinogenemia management and hemostasis testing for coagulopathic patients.

A survey of US hospitals on platelet inventory management, transfusion practice, and platelet availability.

BACKGROUND: A survey of US hospitals was conducted to increase our understanding of the current state of platelet (PLT) practice and supply. The survey captures information on transfusion practice and inventory management, including stock levels, outdate rates, ability to return or transfer PLTs, and low dose PLTs. Notably, the survey also elucidates PLT availability challenges and impact to patient care. STUDY DESIGN AND METHODS: A 27 question online survey was distributed directly to over 995 US hospitals and indirectly through blood centers to many more between September 27 and October 25, 2019. Descriptive statistics were used for respondent characteristics. Bivariate analysis was performed and correlation coefficients, chi square tests, and p values determined statistical significance of relationships between variables. RESULTS: Four hundred and eighty-one hospitals completed the survey of which 21.6%, 53.2%, and 25.2% were characterized as small, medium, and large hospitals, respectively. Some key observations from this survey include: (1) there is an opportunity for greater adherence to evidence-based guidelines; (2) higher outdate rates occur in hospitals stocking less than five PLTs and the ability to return or transfer PLTs lowers outdates; (3) use of low dose apheresis PLTs varies; and (4) decreased PLT availability is commonly reported, especially in hospitals with high usage, and can lead to delays in transfusions or surgeries. CONCLUSION: This survey represents a comprehensive national assessment of inventory management practices and PLT availability challenges in US hospitals. Findings from this survey can be used to guide further research, help shape future guidance for industry, and assist with policy decisions.

Sequential dosing of convalescent COVID-19 plasma with significant temporal clinical improvements in a persistently SARS-COV-2 positive patient.

The current global pandemic, SARS-CoV-2 infection, is still extending across the world affecting millions of lives to the date. While new successful vaccines are available with promising outcomes to minimize the spread and to reduce the severity of the disease, optimal therapeutic options still remain elusive. COVID-19 convalescent plasma (CCP) is an investigational treatment option which studies suggesting signals of efficacy and favorable outcomes only for patients treated very early in course of the disease. Benefits of the use of CCP later in the disease remain highly debated and therefore are not common practice. We hereby report a case of severe SARS-CoV-2 infection in a young male patient with prolonged COVID-19 positivity who received repeat doses of CCP treatments later in the disease with temporal clinical improvement. This patient's case highlights the need of further studies evaluating efficacy of repeated dosing of CCP. This also suggests a potential of successful use of CCP later in the disease in selected COVID-19 patients.

Blood transfusions in gunshot-wound-related emergency department visits and hospitalizations in the United States.

BACKGROUND: The United States (US) leads all high-income countries in gunshot wound (GSW) deaths. However, previous US studies have not evaluated the national blood transfusion utilization patterns in hospitalized GSW patients. METHODS: Data from 2016 to 2017 were analyzed from the Nationwide Emergency Department Sample (NEDS) and Nationwide Inpatient Sample (NIS), the largest all-payer emergency department (ED) and inpatient databases, respectively. Using stratified probability sampling, weights were applied to generate nationally representative estimates. Multivariable Poisson-regression models were used to estimate prevalence ratios (PR) of blood transfusion. RESULTS: There were 168,315 ED visits and 58,815 hospitalizations (age = 18-90 years) following a GSW. The majority of hospitalizations were men (88.5%), age 18-24 years (31.8%), and assault-related GSW (51.3%). Blacks had the largest proportion (48.7%) overall of all GSW hospitalizations; Whites accounted for the highest proportion of intentional self-harm injuries (72.4%). Blood transfusions occurred in 12.7% of hospitalizations (12.0% red blood cell [RBC], 4.9% plasma, and 2.5% platelet transfusions). Only 1.9% of cases were associated with transfusion of all three blood components. Hospitalizations with major/extreme severity of illness had significantly higher prevalence of transfusion versus those with mild/moderate severity [crude PR = 4.79 (95%CI:4.15-5.33, p < .001)]. Overall, 8.2% of hospitalizations with GSW died, of whom 26.8% required blood transfusions, which was significantly higher than survivors [crude PR = 2.34 (95%CI:2.10-2.61, p < .001)]. The vast majority (95%) of the transfusions among those who died were within 48 h since admission. CONCLUSIONS: Gun-related violence is a public health emergency in the US, and GSWs are a source of significant mortality, blood utilization, and health care costs.

Impact of the early coronavirus disease 2019 pandemic on blood utilization in the United States: A time-series analysis of data reported to the National Healthcare Safety Network Hemovigilance Module.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has disrupted healthcare services worldwide. However, little has been reported regarding the impact on blood utilization. We quantified the impact of COVID-19 on blood utilization and discards among facilities reporting to the National Healthcare Safety Network Hemovigilance Module. METHODS: Facilities continuously reporting data, during January 2016-June 2020, on transfused and discarded blood components, stratified by component type (red blood cells [RBC], platelets, and plasma), were included. Interrupted time-series analysis with generalized estimating equations, adjusting for facility surgical volume and seasonality, was used to quantify changes in blood utilization and discards relative to a Centers for Medicare & Medicaid Services notification delaying nonessential medical procedures (March 2020). RESULTS: Seventy-two facilities included in the analyses, on average, transfused 44,548 and discarded 2,202 blood components monthly. Following the March 2020 notification and after multivariable adjustment, RBC and platelet utilization declined, -9.9% (p < .001) and -13.6% (p = .014), respectively. Discards increased for RBCs (30.2%, p = .047) and platelets (60.4%, p = .002). No statistically significant change in plasma was found. Following these abrupt changes, blood utilization and discards rebounded toward baseline with RBC utilization increasing by 5.7% (p < .001), and platelet and RBC discards decreasing -16.4% (<0.001) and -12.7 (p = .001), respectively. CONCLUSION: Following notification delaying elective surgical procedures, blood utilization declined substantially while blood discards increased, resulting in substantial wastage of blood products. Ongoing and future pandemic response efforts should consider the impact of interventions on blood supply and demand to ensure blood availability.

Buffy coat platelets coming to America: Are we ready?

BACKGROUND: Buffy coat (BC) platelets (PLTs) have been used globally for many years. In 2004 Canadian Blood Services (CBS) made the decision to transition from PLT-rich plasma (PRP) to BC PLTs. We reviewed the benefits and manufacture process of BC and the implementation challenges involved. STUDY DESIGN AND METHODS: A literature review was performed in the following areas: BC efficacy, donor population shifts, production and good stewardship of PLTs, logistic considerations with overnight holds, advantages of the overnight hold, the CBS experience, licensure and standards, and changes needed to produce BC PLTs in the United States. The aim was to analyze current practice and identify possible actions for blood centers and hospitals. RESULTS: Implementation of BC would offer an additional source of PLTs to address the growing elderly population and the declining apheresis donor base. Substantial logistic, operational, and financial benefits were seen when CBS transitioned to BC with overnight hold. CONCLUSIONS: Buffy coat blood products are widely used throughout the world. Recent conversion from PRP to BC by CBS showed that conversion can be accomplished with planning, communication, and partnership from all stakeholders. In conclusion, BC PLTs are worth serious consideration in the United States, but regulatory barriers in the United States will need to be addressed.

Comparative changes of pre-operative autologous transfusions and peri-operative cell salvage in the United States.

BACKGROUND: With improved safety of allogeneic blood supply, the use of preoperative autologous donations (PADs) and perioperative autologous cell salvage (PACS) has evolved. This study evaluated temporal trends in PAD and PACS use in the United States. METHODS: The National Inpatient Sample database, a stratified probability sample of 20% of hospitalizations in the United States, was used to compare temporal trends in hospitalizations reporting use of PADs and PACS from 1995 to 2015. Factors associated with their use were examined between 2012 and 2015 with use of multivariable Poisson regression. Sampling weights were applied to generate nationally representative estimates. RESULTS: There was a steady decrease in hospitalizations reporting PAD transfusions from 27.90 per 100 000 in 1995 to 1.48 per 100 000 hospitalizations in 2015 (P-trend <.001). In contrast, PACS increased from a rate of 1.16 per 100 000 in 1995 to peak of 20.51 per 100 000 hospitalizations in 2008 and then steadily declined (P-trend<.001). Higher odds of PACS and PADs were observed in older patients, elective procedures (vs urgent), and urban teaching/nonteaching hospitals (vs rural hospitals) (P < .001). PACS was more common in hospitalizations in patients with higher levels of severity of illness as compared to those with minor severity (adjusted prevalence ratio [adjPR], 2.39; 95% confidence interval [CI], 2.08-2.73; P<.001), while PADs were performed less often in patients with higher underlying severity of illness (All Patient Refined Diagnosis Related Groups, 4 vs 1, adjPR, 0.61; 95% CI, [0.39-0.95]; P = .028). CONCLUSIONS: There was a significant decrease in PAD red blood cell transfusions, while PACS has increased and subsequently decreased; PACS plays an important role in surgical blood conservation. The subsequent decline in PACS likely reflects further optimization of transfusion practice through patient blood management programs and improvement of surgical interventions.

Rapid establishment of a COVID-19 convalescent plasma program in a regional health care delivery network.

BACKGROUND: COVID-19 convalescent plasma (CCP) represents an appealing approach to the treatment of patients with infections due to SARS-CoV-2. We endeavored to quickly establish a sustainable CCP transfusion program for a regional network of health care facilities. STUDY DESIGN AND METHODS: A regional collaborative group was activated to address the issues necessary to implementing a CCP transfusion program and making the program sustainable. A wide range of health care providers including physicians (critical care, infectious disease, transfusion medicine), nurses, pharmacists, laboratorians, and information technology (IT) specialists were required to make the program a success. RESULTS: The CCP implementation team initially consisted of four members but quickly grew to a group of nearly 20 participants based on different issues related to program implementation. Overall, six major implementation "themes" were addressed: (a) registration of individual hospitals and principal investigators with a national investigational new drug research protocol; (b) collaboration with a regional blood donor center; (c) targeted recruitment of convalesced donors; (d) IT issues related to all aspects of CCP ordering, distribution, and transfusion; (e) prioritization of patients to receive CCP; and (f) evaluation of CCP products including antibody characteristics and patient response to therapy. CONCLUSION: Within 4 weeks of initiation, CCP was successfully transfused at multiple hospitals in our regional health care delivery system. A program infrastructure was established that will make this program sustainable into the future. This approach has broader implications for the success of multi-institutional programs requiring rapid implementation.

Evaluation of donor informed consents and associated predonation educational materials in the United States and Canada: variability in elements of consent and measures of readability and reading burden.

BACKGROUND: Every day, approximately 30,000 donors present to blood collection establishments in the United States or Canada, where they are provided information about donation and asked to sign a consent before donating. We evaluated elements of informational and consent documents and measures of readability that may influence their comprehension. MATERIALS AND METHODS: Consents for whole blood (WB) and automated collections and predonation reading materials (PRMs) representing over 93% of WB collections in the United States and Canada were evaluated. Elements, including risks of donation, were cataloged. Word count, Flesch-Kinkaid (F-K) reading ease/grade level scores, Simple Measure of Gobbledygook grade, and percentage of complex words were measured. RESULTS: F-K grade levels ranged from 9.2 to 16.9 for WB consents, 7.8 to 16.0 for apheresis consents, and 6.7 to 10.9 for PRMs, above the recommended level of eighth grade or lower for general audiences. F-K reading ease scores were below the cutoff of 60 for readability. Reading burden was substantial, with word count ranging from 131 to 885, 131 to 996, and 649 to 2743 for WB and apheresis consents and PRMs, respectively. Use of jargon and the absence of consent elements such as confidentiality, voluntariness, ability to withdraw consent, and risks of deferral were common. CONCLUSIONS: Donor consent documents and associated materials vary widely, are written at challenging grade levels, present considerable reading burden, contain substantial jargon, and are missing key elements of consent. The authors recommend an organized effort, including blood donors, legal experts, and blood collection experts, to reach consensus on the minimal requirements for standardized clear and concise consent documents in an optimized format.