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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 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 (

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.

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

BACKGROUND: Factors associated with red blood cell (RBC), plasma, and platelet transfusions in hospitalized neonates and children across the United States have not been well characterized. METHODS: Data from the Kids’ Inpatient Database (KID) 2016 were analyzed. KID is a random sample of 10% of all uncomplicated in-hospital births and 80% of remaining pediatric discharges from approximately 4200 US hospitals. Sampling weights were applied to generate nationally representative estimates. Primary outcome was one or more RBC transfusion procedures; plasma and platelet transfusions were assessed as secondary outcomes. Analysis was stratified by age: neonates (NEO; ≤28 d), and nonneonates (PED; >28 d and

Severe acute respiratory syndrome coronavirus 2 (SARS–CoV-2), the cause of coronavirus disease 2019 (COVID-19), has spurred a global health crisis. To date, there are no proven options for prophylaxis for those who have been exposed to SARS–CoV-2, nor therapy for those who develop COVID-19. Immune (i.e., “convalescent”) plasma refers to plasma that is collected from individuals following resolution of infection and development of antibodies. Passive antibody administration through transfusion of convalescent plasma may offer the only short-term strategy for conferring immediate immunity to susceptible individuals. There are numerous examples in which convalescent plasma has been used successfully as postexposure prophylaxis and/or treatment of infectious diseases, including other outbreaks of coronaviruses (e.g., SARS-1, Middle East respiratory syndrome [MERS]). Convalescent plasma has also been used in the COVID-19 pandemic; limited data from China suggest clinical benefit, including radiological resolution, reduction in viral loads, and improved survival. Globally, blood centers have robust infrastructure for undertaking collections and constructing inventories of convalescent plasma to meet the growing demand. Nonetheless, there are nuanced challenges, both regulatory and logistical, spanning donor eligibility, donor recruitment, collections, and transfusion itself. Data from rigorously controlled clinical trials of convalescent plasma are also few, underscoring the need to evaluate its use objectively for a range of indications (e.g., prevention vs. treatment) and patient populations (e.g., age, comorbid disease). We provide an overview of convalescent plasma, including evidence of benefit, regulatory considerations, logistical work flow, and proposed clinical trials, as scale-up is brought underway to mobilize this critical resource.

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.

Passive immunotherapy has been used since the late 19th century, and in 1901, the first Nobel Prize in Physiology or Medicine was awarded for serum therapy for patients with diphtheria. During the ...

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% (

Background The prevalence of iron depletion is high among premenopausal women who donate blood frequently. Studies in nondonor populations indicate that iron deficiency anemia is associated with an increased risk of low birth weight. This prompts concerns that iron deficiency induced by frequent blood donation might impair subsequent fetal development. Study design and methods The aim of this study was to assess whether prepregnancy donation intensity affects the birth weight of singletons born at term (gestational week 38 or later) to nulliparous female donors in Denmark. We identified 293,897 first live singleton births to Danish women between 1997 and 2012 with complete information on gestational age, birth weight, child sex, parental age, maternal smoking status during pregnancy, and parental education length and annual income. Linear regression analysis was applied, with birth weight as outcome, number of donations within the 3 years before pregnancy as the explanatory variable, and confounding variables as described. Results Birth weight among children of low-intensity donors (n = 22,120) was 12.6 g (95% confidence interval, 6.7-18.6) higher than nondonors (n = 268,253) after controlling for the above-mentioned factors. The higher birth weight among low-intensity donors can be explained by the healthy donor effect. In fully adjusted analyses, birth weight among children of high-intensity donors (n = 3,524) was 20.2 g (95% confidence interval, 5.1-35.3 g) lower compared with low-intensity donors. This reduced birth weight among high-intensity donors compared to low-intensity donors may reflect blood donation-induced iron deficiency. Conclusions Our results show that high prepregnancy donation intensity is inversely associated with birth weight of singletons born at term to nulliparous women.

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 healthcare 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 healthcare providers including physicians (critical care, infectious disease, transfusion medicine), nurses, pharmacists, laboratorians, and information technology specialists were required to make the program a success. RESULTS The CCP implementation team initially consisted of 4 members but quickly grew to a group of nearly 20 participants based on different issues related to program implementation. Overall, 6 major implementation “themes” were addressed: (1) registration of individual hospitals and principle investigators with a national investigational new drug research protocol, (2) collaboration with a regional blood donor center, (3) targeted recruitment of convalesced donors, (4) information technology issues related to all aspects of CCP ordering, distribution, and transfusion, (5) prioritization of patients to receive CCP, and (6) 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 healthcare 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.

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.

KEY IDEAS Oral swabs, sputum, and blood samples from 18 asymptomatic and symptomatic patients with SARS‐CoV‐2 infection were examined using RT‐PCR testing in order to assess the risk of transfusion‐related transmission.In asymptomatic patients as well as patients with flu‐like symptoms and fever, no SARS‐CoV‐2 RNA could be detected in the blood or serum despite a clearly positive result in all throat swabs.As patients with symptoms of infectious disease will not be admitted to blood donation, the risk for transfusion transmission of SARS‐CoV‐2 seems to be negligible.

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.

On March 24, 2017, more than 90 experts in blood safety and international development from blood centers, industry, government, and international and nongovernmental organizations gathered in Arlington, Virginia, for the Third International Blood Safety Forum, cosponsored by America's Blood Centers and Global Healing. This report summarizes presentations and major conclusions. The meeting explored ways to increase access to affordable, safe blood for low- and lower-middle-income countries (LMICs) in an era when funding from the US President's Emergency Plan for AIDS Relief (PEPFAR) and the Global Fund has been redirected from preventing the spread of human immunodeficiency virus (HIV) to diagnosing and treating the 25 million-plus people living with HIV in LMICs. More effective management systems must be developed to improve cost recovery for blood. While blood systems become more sustainable, continued investment is required to keep them operating. The traditional model of large grants from bilateral and multilateral donors will need to be supplemented (or replaced) with public-private partnerships and nongovernmental investment. A continued emphasis on quality is fundamental. Blood systems must build quality programs, based on accepted standards, including hospitals, clinics, and rural health care providers to ensure proper and safe use of blood. Proposals to resolve health care inequities between LMICs and high-income countries (HICs) must include helping LMICs to define sustainable national policies and practices for blood availability and utilization to suit local contexts. The blood safety lexicon should be revised to include availability, accessibility, and affordability of safe blood and blood products as the goal of all blood safety initiatives.

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.

Background Effective and financially viable mitigation approaches are needed to reduce bacterial contamination of platelets in the US. Expected costs of large-volume delayed sampling (LVDS), which would be performed by a blood center prior to shipment to a hospital, were compared to those of pathogen reduction (PR), point-of-release testing (PORt), and secondary bacterial culture (SBC). Methods Using a Markov-based decision-tree model, the financial and clinical impact of implementing all variants of LVDS, PR, PORt, and SBC described in FDA guidance were evaluated from a hospital perspective. Hospitals were assumed to acquire leukoreduced apheresis platelets, with LVDS adding $30 per unit. Monte Carlo simulations were run to estimate the direct medical costs for platelet acquisition, testing, transfusion, and possible complications associated with each approach. Input parameters, including test sensitivity and specificity, were drawn from existing literature and costs (2018US$) were based on a hospital perspective. A one-way sensitivity analysis varied the assumed additional cost of LVDS. Results Under an approach of LVDS (7-day), the total cost per transfused unit is $735.78, which falls between estimates for SBC (7-day) and PORt. Assuming 20,000 transfusions each year, LVDS would cost $14.72 million annually. Per-unit LVDS costs would need to be less than $22.32 to be cheaper per transfusion than all other strategies, less than $32.02 to be cheaper than SBC (7-day), and less than $196.19 to be cheaper than PR (5-day). Conclusions LVDS is an effective and cost-competitive approach, assuming additional costs to blood centers and associated charges to hospitals are modest.

BACKGROUND Women who donate blood on a regular basis are at high risk of becoming iron depleted. Iron deficiency anemia has been shown to increase the risk of low birthweight and possibly preterm birth. Therefore, there is a concern that regular blood donation by female donors might adversely impact the well-being of their offspring. This retrospective cohort study examined the association between blood donation and the occurrence of adverse pregnancy outcomes. STUDY DESIGN AND METHODS The study sample included 18,483 female blood donors in their childbearing years (age 18 to 45 years) who delivered during the period 2001 to 2011 in the province of Quebec (Canada). The occurrence of low birthweight (

In 2014, the College of American Pathologists (CAP) Transfusion Medicine Resource Committee (TMRC) reported the results of a survey of more than 3100 laboratories concerning their policies and procedures for testing serological weak D phenotypes and administration of Rh immune globulin (RhIG).1 Among the findings of this survey is the observation that there is a lack of standard practice in the United States for interpreting the RhD type when a serological weak D phenotype is detected. In some laboratories, an individual with a serological weak D phenotype, especially if a blood donor, is interpreted to be RhD-positive. In the same or other laboratories, especially if a serological weak D phenotype is detected in a female of child-bearing potential, the individual is likely to be managed as RhD-negative for transfusions and, if pregnant, considered a candidate for RhIG. Also, the performance characteristics of serological typing methods for RhD vary. For patients, including pregnant women, the majority of laboratories have policies and procedures that do not use the indirect antiglobulin (weak D) test, thereby avoiding detection of a serological weak D phenotype so that the RhD type will be interpreted to be RhD-negative. Other laboratories typically perform a weak D test for the same category of patients. For blood donors and newborns, it is standard practice for laboratories to have policies and procedures for RhD typing to ensure that serological weak D phenotypes are detected and interpreted as RhD-positive.1 The goal of these RhD typing practices is to protect RhD-negative persons from inadvertent alloimmunization to the D antigen by exposure to RhD-positive RBCs, including RBCs expressing a serological weak D phenotype. Although there has not been a recent prospective study in the United States, it is estimated that current RhD typing practice, together with contemporary obstetrical practices for administration of antepartum and postpartum RhIG, is 98.4 to 99 percent successful in preventing RhD alloimmunization and RhD hemolytic disease of the fetus/newborn.2 However, there are unwarranted consequences associated with the practice of not determining the RHD genotype of persons with a serological weak D phenotype, including unnecessary injections of RhIG and transfusion of RhD-negative RBCs -- always in short supply -- when RhD-positive RBCs could be transfused safely. CAP’s TMRC reviewed the current status of RHD genotyping and proposed that selective integration of RHD genotyping in laboratory practices could improve the accuracy of RhD typing results, reduce unnecessary administration of RhIG in women with a serological weak D phenotype, and decrease unnecessary transfusion of RhD-negative RBCs to recipients with a serological weak D phenotype.1 In response to the findings of the CAP TMRC survey, AABB and CAP convened a Work Group on RHD Genotyping and charged it with developing recommendations to clarify clinical issues related to RhD typing in persons with a serological weak D phenotype. As an initial step for formulating recommendations, the Work Group reviewed the current state of molecular science of RHD, including more than 140 publications covering background;1-12 D variants with anti-D;13-29 molecular basis of serological weak D phenotypes;30-92 reviews, editorials and commentaries;93-129 technical resources;130-142 and standards and guidelines.143-149 This Commentary summarizes the proceedings and recommendations of the Work Group.

Molecular diagnostics is a key component of laboratory medicine. Here, the authors review key triggers of ever-increasing automation in nucleic acid amplification testing (NAAT) with a focus on specific automated Polymerase Chain Reaction (PCR) testing and platforms such as the recently launched cobas® 6800 and cobas® 8800 Systems. The benefits of such automation for different stakeholders including patients, clinicians, laboratory personnel, hospital administrators, payers, and manufacturers are described. Areas Covered: The authors describe how molecular diagnostics has achieved total laboratory automation over time, rivaling clinical chemistry to significantly improve testing efficiency. Finally, the authors discuss how advances in automation decrease the development time for new tests enabling clinicians to more readily provide test results. Expert Commentary: The advancements described enable complete diagnostic solutions whereby specific test results can be combined with relevant patient data sets to allow healthcare providers to deliver comprehensive clinical recommendations in multiple fields ranging from infectious disease to outbreak management and blood safety solutions.

As Ebola virus has infected thousands of individuals in West Africa, there is growing concern about the appropriate response of hospitals in developed nations caring for patients and handling laboratory specimens for patients suspected of Ebola virus disease (EVD). Guidelines for caring for EVD patients are proliferating rapidly from national and state public health authorities, professional societies, and individual hospitals. It is no surprise that they differ from one another, and some very conservative recommendations call for suspension of routine laboratory testing, including pretransfusion testing. EVD is transmitted by direct contact with blood, secretions, organs, and other body fluids and not by airborne routes. Based on experimental and observational data, the US Centers for Disease Control and Prevention (CDC) recommends that clinicians follow contact and droplet precautions. Laboratory personnel are required to follow the blood-borne pathogen standard, especially the use of appropriate barriers consisting of gloves, gown, goggles, mask to cover nose and mouth, and plexiglass shield, where splashes of potentially infectious materials may be generated. Their recommendations are permissive of clinically appropriate laboratory testing, including pretransfusion testing, using barrier isolation precautions. Most individuals with suspected EVD will have a fever of another etiology, such as Plasmodium falciparum malaria. We believe that forgoing all routine pretransfusion laboratory testing may result in a greater increase in poor clinical outcomes than any diminution in the risks to laboratory personnel will justify. It is imperative for all laboratory directors, working with institutional infection control and safety personnel, to evaluate their hospital policies for potentially infectious patients and provide a safe environment for their patients and employees.

Background Testing of platelets (PLTs) for bacterial contamination is required by the AABB Standards but is not fully standardized. On January 31, 2011, a new AABB Standard, 5.1.5.1.1, specified that bacterial detection methods for PLT components shall use assays either approved by the Food and Drug Administration (FDA) or validated to provide sensitivity equivalent to these FDA-approved methods. Methods An Internet-based survey of AABB member institutions was conducted from May to June 2012, to document current practices used in 2011 for bacterial detection in different PLT products and to assess the impact of the new standard. Results Of 1053 AABB member institutions surveyed, 40 of 99 blood centers (40.4%) and 184 of 954 hospital blood banks or transfusion services (19.3%) responded. Sixty-four respondents manufactured PLTs. Apheresis PLTs (APs) were predominantly screened with the BacT/ALERT system (89.5%); the majority (95.2%) were cultured with at least 8 mL of product. There was substantial variation in the minimum incubation time of cultures before release of PLTs (range, 0 to >24 hr). Recalls of released AP for possible bacterial contamination were largely successful (67.3%); successful interdiction before transfusion was associated with incubation for more than 12 hours before release (p

Zika virus can be transmitted by transfusion, but the harm caused to recipients is not clear in most cases. It is very likely that the virus could also be transmitted by transplanted organs. Sensitivity to the risk from transfusion is elevated by consideration of possible severe neurologic damage in fetuses. Strategies for dealing with transfusion risk vary with the presence of Zika in the region. In nonendemic areas, risks can be reduced by excluding donors who have exposure through travel or sexual contact with someone at risk. In both endemic and nonendemic areas, the risk can be further reduced by nucleic acid testing of donors, or pathogen reduction of platelet and plasma products. The real risk to the population depends on the frequency of infection as well as the efficacy of these interventions. The interventions chosen will depend on the risk assessment for any situation; in the United States at this time, a combination of travel deferrals, testing, and, to a lesser extent, pathogen reduction is being used, but universal testing of US blood donors under investigational use has been mandated by the US Food and Drug Administration, beginning with states most at risk of local transmission. Canada is largely using travel deferrals. A precautionary approach may be taken; however, a formal decision-making framework has been suggested. The situation globally is clearly very fluid, as the epidemic continues to spread and we continue to learn how to best protect recipients of blood and transplants.

International survey on NAT testing of blood donations : expanding implementation and yield from 1999 to 2009.

The alternative pathway of the complement cascade plays a role in the pathogenesis of dense deposit disease (DDD). Deficiency of complement factor H and mutations in CFH associate with the development of DDD, but it is unknown whether allelic variants in other complement genes also associate with this disease. We studied patients with DDD and identified previously unreported sequence alterations in several genes in addition to allelic variants and haplotypes common to patients with DDD. We found that the likelihood of developing DDD increases with the presence of two or more risk alleles in CFH and C3. To determine the functional consequence of this finding, we measured the activity of the alternative pathway in serum samples from phenotypically normal controls genotyped for variants in CFH and C3. Alternative pathway activity was higher in the presence of variants associated with DDD. Taken together, these data confirm that DDD is a complex genetic disease and may provide targets for the development of disease-specific therapies.

BACKGROUND: As part of its risk management process, Canadian Blood Services (CBS) constructed mathematical models of how newly emerging pathogens might affect blood transfusion recipients. STUDY DESIGN AND METHODS: CBS convened an expert panel including medical, health economics, analytical, risk management, and insurance professionals to examine multiple data sources. The model for emerging pathogen risk included separate modules to calculate the frequency and severity of infections from transfusion-transmitted agents that could cause either acute transient or chronic persistent infection. Important model input variables were annual number of components transfused, the presumed incidence and prevalence of a new agent, the time interval of recipient risk, recipient age and sex, projected recipient survival, rate of secondary infection, pathogen-induced morbidity, and the associated medical costs of such morbidity. RESULTS: In the 5-year time frame considered in the model, it was estimated that approximately 3500 recipient infections (two-SD range of 0 to 11,370 infections) could occur from an emerging pathogen that establishes a chronic infection in donors, with 60% of these due to red blood cell transfusion. The medical costs associated with recipient outcomes due to a catastrophic emerging pathogen could be lowered by 20% if an effective pathogen reduction method for either platelets or plasma were in place. CONCLUSION: This modeling exercise offers a framework for other blood services to construct similar models. It also provides a useful way to model the implementation of new blood safety interventions (e.g., pathogen reduction) on emerging pathogen risk.

BACKGROUND: Emerging infections have been identified as a continuing threat to human health. Many such infections are known to be transmissible by blood transfusion, while others have properties indicating this potential. There has been no comprehensive review of such infectious agents and their threat to transfusion recipient safety to date. STUDY DESIGN AND METHODS: The members of AABB's Transfusion Transmitted Diseases Committee reviewed a large number of information sources in order to identify infectious agents with actual or potential risk of transfusion transmission now or in the future in the US or Canada; with few exceptions, these agents do not have available interventions to reduce the risk of such transmission. Using a group discussion and writing process, key characteristics of each agent were identified, researched, recorded and documented in standardized format. A group process was used to prioritize each agent on the basis of scientific/epidemiologic data and a subjective assessment of public perception and/or concern expressed by regulatory agencies. RESULTS: Sixty-eight infectious agents were identified and are described in detail in a single Supplement to TRANSFUSION. Key information will also be provided in web-based form and updated as necessary. The highest priorities were assigned to Babesia species, Dengue virus, and vCJD. CONCLUSION: The information is expected to support the needs of clinicians and transfusion medicine experts in the recognition and management of emerging infections among blood donors and blood recipients.

HIV was present in 1.1% of transfused blood during the early 1980s in some communities [1]. Perceived shortcomings in the response of the blood community, regulators, and public health authorities led to an exceptionally precautionary approach to transfusion-transmitted infections [2]. In return for unprecedented protection of transfusion recipients, blood donors have since been subjected to behavioral interrogation and testing, which uses 9 assays for 6 transfusion-transmissible infections, with great success. Behavioral deferrals (blood donor deferrals for high-risk behaviors) are surrogates, usually developed in the absence of acceptable laboratory tests, and they are blunt instruments. Still, for HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV), donor recruitment and interviewing reduce the prevalence of infection in donations from first time blood donors by ~80% [3], compared with the US population. Behavioral deferrals are retained after test deployment as a layer of

Purpose of review To describe new developments in blood-bank screening and management of patients with chronic Trypanosoma cruzi infection in the United States. Recent findings The first US Food and Drug Administration licensed serological test for T. cruzi blood screening went into widespread usage in January 2007. More than 500 confirmed T. cruzi-infected donations were detected by mid-June 2008. Until recently, drug therapy was recommended for acute and congenital infections, but seldom for chronic infections, which were believed to respond poorly. However, in the 1990s, efficacy was demonstrated in two placebo-controlled trials of benznidazole in children with chronic T. cruzi infection. In 2006, a nonrandomized, nonblinded trial demonstrated that benznidazole treatment may slow progression of cardiomyopathy and decrease mortality risk in infected adults. Summary Blood-bank screening will continue to detect T. cruzi-infected donors. Based on recent data, antitrypanosomal treatment is recommended for all acute and congenital T. cruzi infections, reactivated infection, and chronically infected children. In adults aged 19–50 years without advanced heart disease, treatment should generally be offered; management should be individualized for older adults. Less toxic, more effective drugs, a sensitive, specific assay for response to treatment, and improved healthcare access would promote more effective management.

There is a substantial literature suggesting that computer-assisted interviewing has advantages over face-to-face and written self-administration of interviews in venues eliciting sensitive information similar to that sought in blood donor history screening. We review some of the recent developments in blood donor history screening, the evidence suggesting that automated interviews should be useful, and the experience to date using computer interviews for blood donation. These data suggest that automated computer-assisted interviewing increases the elicitation of behaviors associated with the risk of transfusion-transmissible infection in donors, improves donor and staff satisfaction, and reduces errors and omissions that frequently accompany traditional interviewing methods. Food and Drug Administration-cleared systems for computer-assisted self-interview of blood donors are briefly described.

the major source of the residual risk of transfusion-transmitted infections. The rates and characteristics of these infections inform decisions about further safety interventions. These data can also validate and supplement public health surveillance; for example, the real-time tracking of largely asymptomatic donor West Nile virus infections, with coverage of the entire country, often provides the earliest evidence of human activity in a region. In this issue of the Journal of Infectious Diseases, 2 articles add to the body of information generated through analysis of sample repositories from blood donors. These studies suggest that we may be underusing the resource that donors represent for the study of infectious diseases in the United States and globally. Even before the recent H1N1 pan

Remarkable progress has been made in transfusion safety from infection over the past three decades. Donor deferrals for at-risk behaviors, the introduction of more-sensitive viral-screening assays and the recent introduction of nucleic-acid amplification technology have nearly eliminated transmission of HIV and hepatitis C virus (HCV) by blood transfusion in North America. Nevertheless, risks of other infectious agents for which such robust screening tools have not been developed, such as bacteria and parasites, still remain. As a result of these successes, the non-infectious risks such as misidentification of patients and inadequate and inappropriate transfusion have become the primary sources of transfusion risk.

Purpose of review In this short review, several emerging agents are described to demonstrate potential responses of the blood community to emerging and potentially emerging infections. Recent findings Critical questions are raised as we consider appropriate approaches to these agents. Can we identify risk thresholds below which interventions are not required, that is, are there tolerable infectious risks of transfusion? Who are the stakeholders responsible for that determination? What is the role of health economic analysis for informing those decisions? If we decide that cost-utility thresholds for transfusion medicine are appropriately several fold higher than for the rest of clinical medicine, who has responsibility for being certain whether those priorities are funded? Summary Four agents will be discussed to highlight the evolving considerations in response to these considerations.

We (the blood community and the regulators) are unable to articulate an answer to the question "how safe is safe enough?" for the set of blood safety measures we have already implemented.We must address this fundamental policy issue to establish priorities for our menu of potential future threats and interventions and to move solutions through development and deploy them with the urgency their importance demands. The experience of four decades with no recognized transfusion-transmitted syphilis during which we have implemented a manylayered approach to blood safety addressing a substantial proportion of the risk of T. pallidum infection in the donor base suggests that the time is ripe to reconsider the use of STS. (excerpt)

B y way of background for the study linking blood and hospital revenue, it is important to know that in the United States, blood helps save more than four million patient lives each year. According to a 1998 study by the U.S. General Accounting Office, about half of all transfusions are considered urgent and life-saving. In 2005, U.S. hospitals’ blood bill was approximately $5 billion; that is what hospitals paid America’s Blood Centers (ABC) members, Red Cross centers, and the smaller number of centers that are not affiliated with either of those two organizations. In the United States, blood represents—and I am sure this is true in most countries of the world—less than 1 percent of total hospital expenses. In the United States, this is approximately $5 billion out of around $600 billion in hospital expenses. On the other hand, our study found that transfusion-related costs are far higher within the hospital when you add all the crossmatching and costs to administer the transfusion. Anything related to a transfusion comes up to about 4.2 percent of total hospital expenses. According to our estimates, U.S. hospitals’ blood bills nearly doubled between 1999 and 2005 and blood use has increased more than 10 percent in that same period. This is, of course, in contrast to Europe, where they have seen declines in use of almost 10 percent in the last few years. These cost increases from 1999 to 2005 are in contrast to earlier periods. Figure 1 shows the price of red blood cells (RBCs) charged by members of ABC in the United States from 1985 to 2005. From about 1985 until about 1994, cost increases generally reflect the cost of medical inflation. From about 1994 until 1999, the curve flattens out considerably. This period in the United States we call “the marketshare wars” between the Red Cross and ABC members during which all blood centers lost money and used up their reserves. During that period Red Cross reported losses in excess of $400 million, and losses among ABC members were likely similar. About 1999, someone started waving the white flag and there was subsequently a jump shift in the cost of blood over the next few years. During that same period, most blood centers also switched to leukoreduced blood, which alone cost hospitals about 15 to 20 percent more. So, there were multiple factors leading to the big price increases in U.S. hospital blood bills in the early part of this century: the need to stop losing money and to rebuild infrastructure; the switch from 20 percent leukoreduced to now over 70 percent; the introduction of nucleic acid donor testing for HIV and hepatitis C; the need to replace up to 9 percent of donors or donations lost as a result of “mad cow” deferrals; and inflationary pressures. This huge increase in blood cost, plus a 10 percent increase in blood usage, is why blood costs have gotten onto hospital radar screens. Figure 2 shows the same blood cost data in a very different way by comparing them with the consumer price index for medical care and the producer price index for the general surgical hospitals, which were fairly consistent, ranging from about 3 to 5 percent from 1997 to 2005. In contrast, the median price for RBCs rose more than 25 percent in 1 year. Figure 3 shows hospital versus blood center margins from 1999 to 2005. The 1.3 percent blood center margin for 1999 marks the beginning of when blood centers stopped losing money. Blood margins were still below 5 percent even during those years of double-digit price increases. In contrast, hospitals have consistently had total annual margins of around 4 to 5 percent. It is important to point out that U.S. hospitals actually lose money or break-even on patient care reimbursements, but they make money on their investments. The same could be said for blood centers in the United States. Many lose money on their core business of providing blood components to hospitals, but are profitable overall on the total market basket of services that they provide. ABBREVIATIONS: ABC = America’s Blood Centers; DRG = diagnosis-related group.

Transfusion-transmitted diseases are caused by viruses, bacteria, protozoa, and prions. Examples of the broad spectrum of infections of current interest in the transfusion medicine community are Babesia , malaria and dengue, together with well-established transfusion-transmitted agents such as HIV, HCV and HBV.

Importance More than 100 million units of blood are collected worldwide each year, yet the indication for red blood cell (RBC) transfusion and the optimal length of RBC storage prior to transfusion are uncertain. Objective To provide recommendations for the target hemoglobin level for RBC transfusion among hospitalized adult patients who are hemodynamically stable and the length of time RBCs should be stored prior to transfusion. Evidence Review Reference librarians conducted a literature search for randomized clinical trials (RCTs) evaluating hemoglobin thresholds for RBC transfusion (1950-May 2016) and RBC storage duration (1948-May 2016) without language restrictions. The results were summarized using the Grading of Recommendations Assessment, Development and Evaluation method. For RBC transfusion thresholds, 31 RCTs included 12 587 participants and compared restrictive thresholds (transfusion not indicated until the hemoglobin level is 7-8 g/dL) with liberal thresholds (transfusion not indicated until the hemoglobin level is 9-10 g/dL). The summary estimates across trials demonstrated that restrictive RBC transfusion thresholds were not associated with higher rates of adverse clinical outcomes, including 30-day mortality, myocardial infarction, cerebrovascular accident, rebleeding, pneumonia, or thromboembolism. For RBC storage duration, 13 RCTs included 5515 participants randomly allocated to receive fresher blood or standard-issue blood. These RCTs demonstrated that fresher blood did not improve clinical outcomes. Findings It is good practice to consider the hemoglobin level, the overall clinical context, patient preferences, and alternative therapies when making transfusion decisions regarding an individual patient. Recommendation 1: a restrictive RBC transfusion threshold in which the transfusion is not indicated until the hemoglobin level is 7 g/dL is recommended for hospitalized adult patients who are hemodynamically stable, including critically ill patients, rather than when the hemoglobin level is 10 g/dL (strong recommendation, moderate quality evidence). A restrictive RBC transfusion threshold of 8 g/dL is recommended for patients undergoing orthopedic surgery, cardiac surgery, and those with preexisting cardiovascular disease (strong recommendation, moderate quality evidence). The restrictive transfusion threshold of 7 g/dL is likely comparable with 8 g/dL, but RCT evidence is not available for all patient categories. These recommendations do not apply to patients with acute coronary syndrome, severe thrombocytopenia (patients treated for hematological or oncological reasons who are at risk of bleeding), and chronic transfusion–dependent anemia (not recommended due to insufficient evidence). Recommendation 2: patients, including neonates, should receive RBC units selected at any point within their licensed dating period (standard issue) rather than limiting patients to transfusion of only fresh (storage length: Conclusions and Relevance Research in RBC transfusion medicine has significantly advanced the science in recent years and provides high-quality evidence to inform guidelines. A restrictive transfusion threshold is safe in most clinical settings and the current blood banking practices of using standard-issue blood should be continued.

Description: Although approximately 85 million units of red blood cells (RBCs) are transfused annually worldwide, transfusion practices vary widely. The AABB (formerly, the American Association of Blood Banks) developed this guideline to provide clinical recommendations about hemoglobin concentration thresholds and other clinical variables that trigger RBC transfusions in hemodynamically stable adults and children. Methods: These guidelines are based on a systematic review of randomized clinical trials evaluating transfusion thresholds. We performed a literature search from 1950 to February 2011 with no language restrictions. We examined the proportion of patients who received any RBC transfusion and the number of RBC units transfused to describe the effect of restrictive transfusion strategies on RBC use. To determine the clinical consequences of restrictive transfusion strategies, we examined overall mortality, nonfatal myocardial infarction, cardiac events, pulmonary edema, stroke, thromboembolism, renal failure, infection, hemorrhage, mental confusion, functional recovery, and length of hospital stay. Recommendation 1: The AABB recommends adhering to a restrictive transfusion strategy (7 to 8 g/dL) in hospitalized, stable patients (Grade: strong recommendation; high-quality evidence). Recommendation 2: The AABB suggests adhering to a restrictive strategy in hospitalized patients with preexisting cardiovascular disease and considering transfusion for patients with symptoms or a hemoglobin level of 8 g/dL or less (Grade: weak recommendation; moderate-quality evidence). Recommendation 3: The AABB cannot recommend for or against a liberal or restrictive transfusion threshold for hospitalized, hemodynamically stable patients with the acute coronary syndrome (Grade: uncertain recommendation; very low-quality evidence). Recommendation 4: The AABB suggests that transfusion decisions be influenced by symptoms as well as hemoglobin concentration (Grade: weak recommendation; low-quality evidence).

In the early 1990s, the Department of Health and Human Services (DHHS) asked the Institute of Medicine (IOM) to assess how the government, the private sector, and other stakeholders had responded to the human immunodeficiency virus (HIV) epidemic and its impact on blood safety. In its executive summary published in TRANSFUSION,1 the IOM Committee to Study HIV Transmission Through Blood and Blood Products noted that although stakes were high, decisions had to be made under a cloud of uncertainty and that responses were slowed by imprecise and incomplete knowledge, personal and institutional biases, and ultimately by failures in leadership. Emphasizing that blood safety is a shared responsibility, the IOM Committee issued 14 recommendations related to structure and policy including the designation of a Blood Secretary Director by DHHS, the establishment of a Blood Safety Council by the US Public Health Service (PHS), and several recommendations to the Federal agencies involved in the evaluation of an infectious threat, in particular, the Food and Drug Administration (FDA). Since then, these recommendations have been implemented and the blood safety community (blood collectors, blood safety experts, and relevant Federal agencies) has responded to other emerging infectious disease (EID) threats, such as West Nile virus (WNV) and most recently the xenotropic murine leukemia virus–related virus (XMRV). Responding to any new threat entails assessing the risk to the blood supply and recipients’ health; evaluating how best to manage and/or control each potential risk; and communicating this information to blood donors, recipients, physicians, and the general public. Although the FDA has the regulatory authority to develop guidance documents and new regulations in response to EID threats based on available data, the challenge of generating that data and responding to potential risks requires concerted and coordinated actions by the multiple PHS agencies (Centers for Disease Control and Prevention [CDC], FDA, National Institutes of Health [NIH]) and by the broader transfusion medicine community (AABB and blood providers). It is therefore incumbent upon the transfusion medicine professionals to collect and provide robust data in a timely manner to policymakers to inform their decision process, as well as take an active role in risk communication. All stakeholders must recognize what they can do and provide leadership and timely research and risk assessments. In so doing, they must take a hard look at their responses and learn lessons from history. Such a process does not involve a confirmation or criticism of what has been done in previous responses to potential threats to the blood supply, but an assessment of how responses can be improved for future threats. In the aftermath of the recent XMRV investigation and the inevitable occurrence of future infectious threats, the National Heart, Lung, and Blood Institute (NHLBI) convened an expert task force charged with evaluating how lessons from previous EID blood safety threat assessments could be used to optimize future response strategies. The task force was asked to review and discuss responses to past epidemics and recent EIDs and to consider: What worked? What could have worked better? What data are necessary to assess blood safety risk? Who needs to be engaged in the evaluation of risk; that is, who are the stakeholders? What methods and/or processes need to be in place and when? What resources, infrastructure, and capacity are needed? How best to train future experts? And how can a scientific culture be encouraged that encourages cooperation? In a first session, responses to earlier epidemics were examined, followed by a discussion on responses to recent agents of concern, including an in-depth look at the latest potential threat, XMRV. A general overview of other agents of potential concerns (the horizon) ensued followed by a general discussion on lessons learned and consideration of future strategies. This report summarizes the results of these discussions.

Summary Background and objectives This study was designed to investigate the causes of alternative pathway dysregulation in a cohort of patients with dense deposit disease (DDD). Design, setting, participants, & measurements Thirty-two patients with biopsy-proven DDD underwent screening for C3 nephritic factors (C3Nefs), factor H autoantibodies (FHAAs), factor B autoantibodies (FBAAs), andgeneticvariantsinCFH.C3Nefsweredetectedby:ELISA,C3convertasesurfaceassay(C3CSA),C3CSAwith properdin (C3CSAP), two-dimensional immunoelectrophoresis (2DIEP), and immunofixation electrophoresis (IFE). FHAAs and FBAAs were detected by ELISA, and CFH variants were identified by Sanger sequencing. ResultsTwenty-fivepatients(78%)werepositiveforC3Nefs.ThreeC3Nef-positivepatientswerealsopositivefor FBAAs and one of these patients additionally carried two novel missense variants in CFH .O f the seven C3Nefnegativepatients,onepatientwaspositiveforFHAAsandtwopatientscarriedCFHvariantsthatmaybecausally related to their DDD phenotype. C3CASP was the most sensitive C3Nef-detection assay. C3CASP and IFE are complementary because C3CSAP measures the stabilizing properties of C3Nefs, whereas IFE measures their expected consequence—breakdown of C3b. Conclusions A test panel that includes C3CSAP, IFE, FHAAs, FBAAs, and genetic testing for CFH variants will identify a probable cause for alternative pathway dysregulation in approximately 90% of DDD patients. Dysregulation is most frequently due to C3Nefs, although some patients test positive for FHAAs, FBAAs, and CFH mutations. Defining the pathophysiology of DDD should facilitate the development of mechanism-directed therapies. Clin J Am Soc Nephrol 7: 265–274, 2012. doi: 10.2215/CJN.07900811

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