Acquired platelet storage container leaks and contamination with environmental bacteria: A preventable cause of bacterial sepsis.

BACKGROUND: Apheresis platelets (AP) may be contaminated by environmental bacteria via container defects acquired during processing, transport, storage, or transfusion, as highlighted by a recent series of septic reactions related to Acinetobacter spp. and other bacterial strains. STUDY DESIGN AND METHODS: The frequency and nature of acquired container defect reports to one manufacturer were evaluated from January 2019 to July 2020. The published incidence of contamination and sepsis due to environmental bacteria with culture screened AP in the United States was reviewed for the period of 2010-2019. RESULTS: Review of a manufacturers' records showed 23 US reports of leaks involving 24 containers attributed to postmanufacturing damage, at a rate of 44 per million distributed storage containers. Analysis of returned containers showed evidence of scratches, impressions, and/or piercings. Literature review of US hemovigilance data revealed that environmental bacteria comprised 7% of confirmed positive primary bacterial culture screens, were responsible for 14%-16% of reported septic, and 8 of 28 (29%) fatal reactions with bacterial-culture screened AP. Sepsis cases have been reported with culture screened, point-of-issue (POI) tested, or pathogen-reduced AP. DISCUSSION: Environmental contamination of AP is rare but can cause sepsis. Container damage provides a pathway for contamination after culture screening, POI bacteria testing, or pathogen reduction. Blood collectors and transfusion services should have procedures to ensure proper inspection, handling, storage, and transport of AP to avoid damage and should enhance efforts to detect defects prior to release and to eliminate bacteria from all contacting surfaces to minimize the risk of contamination.

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.

How do I create a partnership between a blood bank and a milk bank to provide safe, pasteurized human milk to infants?

The now 5-year collaboration between the Indiana Blood Center, now Versiti Blood Center of Indiana, and The Milk Bank has increased the number of human milk donors, improved the collection and processing of donor milk, and improved awareness of this lifesaving resource. The Indiana Blood Center provides greater visibility for The Milk Bank, creating more opportunities to reach potential donors, and can provide the screening blood test for potential donors to become approved human milk donors. The resources of the multiple locations of the Indiana Blood Center permitted the formation of new milk depots in five different cities and quicker transportation of donated milk through their active courier system. This partnership most importantly has improved awareness for both lifesaving missions to the communities they serve.

Evaluation and improvement of blood donor educational materials: results from a multicenter randomized controlled trial.

BACKGROUND: Blood collection centers are charged with creating donor educational materials (DnEM) that are easily understood across all prospective donor populations, while addressing mandates and recommendations from regulatory agencies and professional standard setting organizations. Donors must have sufficient information to understand the donation process with its risks and benefits, time to consider options before deciding, and opportunity to choose whether to proceed with or decline donating. The goal of this multisite randomized controlled trial was to evaluate knowledge acquired using standardized DnEM. America's Blood Centers' Working Group (WG) for Donor Education and Communication was formed to evaluate and suggest modifications of these documents. Based on pilot work, a randomized clinical trial was designed to test donor knowledge across a variety of populations. The WG identified several shortcomings in the current DnEM and proposed new DnEM. The new DnEM were tested against the same, current DnEM being used at all three sites (Blood Donor Educational Material, 2016 version 2.0, published in conjunction with the AABB uniform donor history questionnaire). METHODS AND MATERIALS: One-hundred sixty-five first time and returning donors were randomized in a 2x2 model to review either new DnEM or current DnEM. Every participant completed a pre- and post-quiz that tested their understanding of the DnEM. RESULTS: Returning donors had greater baseline knowledge compared to new donors, but new donors improved more versus returning donors. Donors using the new DnEM showed greater improvement in knowledge than those using current DnEM. CONCLUSION: Comprehension of DnEM can be improved. With this sample size the results suggest that the findings are independent of demographic characteristics, but a larger study would be necessary to confirm this.

Anti-Pr antibody induced cold autoimmune hemolytic anemia following pneumococcal vaccination.

While rare, vaccination-induced autoantibodies can occur outside of the pediatric population. This diagnosis should be considered after infectious and lymphoproliferative disorders are ruled out. Clinical management will depend on the individual case, but all patients should be monitored closely.

Evaluation of a new West Nile virus nucleic acid test for screening of blood donations.

BACKGROUND: West Nile virus (WNV) is transmitted to humans through mosquito bites and can be further transmitted to humans through transfusion or transplantation. Because most infected individuals are asymptomatic, blood donor screening is important in areas where WNV is endemic. These studies evaluated the performance of a new test for detection of WNV RNA in blood donations. STUDY DESIGN AND METHODS: Analytical performance evaluation included sensitivity, specificity, inclusivity, and correlation. A clinical specificity study was conducted at four blood donor testing laboratories in parallel with the cobas TaqScreen WNV Test (Roche Molecular Systems, Inc.). RESULTS: The 95% and 50% limit of detection for cobas WNV was 12.9 copies/mL (95% confidence interval [CI], 10.8-16.3) and 2.1 copies/mL (95% CI, 1.9-2.4) for WNV lineage 1, respectively, and 6.2 copies/mL (95% CI, 4.8-8.9) and 1.1 copies/mL (95% CI, 0.8-1.3) for WNV lineage 2, respectively. Clinical specificity was 100% in 10,823 donor samples tested individually (95% CI, 99.966%-100%) and 63,243 tested in pools of 6 (95% CI, 99.994%-100%). Samples of other members of the Japanese encephalitis virus serocomplex, including St Louis encephalitis, Japanese encephalitis, Murray Valley encephalitis, Usutu, and Kunjin viruses were detected by cobas WNV. CONCLUSION: The cobas WNV test for use on the cobas 6800/8800 System, a fully automated test system, demonstrated high sensitivity and specificity and is suitable for the detection of WNV in blood donors.

Sensitivity and specificity of a new automated system for the detection of hepatitis B virus, hepatitis C virus, and human immunodeficiency virus nucleic acid in blood and plasma donations.

BACKGROUND: Use of nucleic acid testing (NAT) in donor infectious disease screening improves transfusion safety. Advances in NAT technology include improvements in assay sensitivity and system automation, and real-time viral target discrimination in multiplex assays. This article describes the sensitivity and specificity of cobas MPX, a multiplex assay for detection of human immunodeficiency virus (HIV)-1 Group M, HIV-2 and HIV-1 Group O RNA, HCV RNA, and HBV DNA, for use on the cobas 6800/8800 Systems. STUDY DESIGN AND METHODS: The specificity of cobas MPX was evaluated in samples from donors of blood and source plasma in the United States. Analytic sensitivity was determined with reference standards. Infectious window periods (WPs) before NAT detectability were calculated for current donor screening assays. RESULTS: The specificity of cobas MPX was 99.946% (99.883%-99.980%) in 11,203 blood donor samples tested individually (IDT), 100% (99.994%-100%) in 63,012 donor samples tested in pools of 6, and 99.994% (99.988%-99.998%) in 108,306 source plasma donations tested in pools of 96. Seven HCV NAT-yield donations and one seronegative occult HBV infection were detected. Ninety-five percent and 50% detection limits in plasma (IU/mL) were 25.7 and 3.8 for HIV-1M, 7.0 and 1.3 for HCV, and 1.4 and 0.3 for HBV. The HBV WP was 1 to 4 days shorter than other donor screening assays by IDT. CONCLUSION: cobas MPX demonstrated high specificity in blood and source plasma donations tested individually and in pools. High sensitivity, in particular for HBV, shortens the WP and may enhance detection of occult HBV.

The Need for Education in Molecular Immunohematology: A Survey of Specialists in Blood Banking.

BACKGROUND: Within transfusion medicine, the education of molecular technologies lacks standardization. OBJECTIVE: To address this problem, we surveyed specialist in blood bank technology (SBBT) programs, immunohematology reference laboratories, and SBBT graduates to define its current state. METHODS: An anonymous online survey (SurveyMonkey) was emailed to the 15 American Association of Blood Banks (AABB) SBBT programs, 59 AABB IRLs, and 82 SBBT graduates. RESULTS: In the didactic portion of the SBBT curriculum, all programs incorporate knowledge base of blood groups, 13 incorporate molecular techniques, and 5 include case studies. Thirteen programs have intentions of expanding the knowledge base in molecular topics. Most IRLs (97%) think SBBT programs should continue to expand molecular knowledge base. Most graduates (94%) believe more molecular topics should be included in the SBBT curriculum; however, only 50% believe they currently apply their molecular knowledge in their post-graduate employment. CONCLUSION: We propose a more descriptive molecular diagnostics curriculum for SBBT programs to help standardize the education of molecular topics.

How do we design, implement, and manage an ongoing program to provide iron supplements to women blood donors?

Here we describe the design and management of Indiana Blood Center's 10-year Iron For Women program, an ongoing community blood center-based program with continual program and donor management providing iron supplements to healthy women blood donors. Donor iron supplementation has typically been limited to research study protocols, for a defined period, with the associated resources and funding. The results of studies have supported the utility of iron supplementation: iron supplementation will enhance dietary iron for increased gastrointestinal absorption triggered as a normal homeostatic response to blood loss, thereby providing a suitable dietary iron source in the event the donor's usual diet lacks sufficient iron. Despite proven results, blood centers have been reluctant to adopt the practice due to barriers such as donor selection, ensuring the appropriateness of iron supplementation relative to the health of the donor, supplement costs, provision logistics, and program management costs. We present here how we designed our program and why it is in the Blood Center's interest to help willing women participate in volunteer blood donation by attempting to mitigate associated iron loss.

Two case studies and a review of paroxysmal cold hemoglobinuria.

Paroxysmal cold hemoglobinuria (PCH) is an acquired hemolytic anemia caused by immunoglobulin G (IgG) antibodies that sensitize red blood cells (RBCs) at cold temperatures by fixing complement to the RBCs causing intravascular hemolysis on rewarming. PCH usually appears in young children as recurrent high fevers, chills, and passage of red-brown urine. The diagnostic test for PCH is the Donath-Landsteiner test, an in vitro assay for biphasic hemolysis. Herein, we present 2 cases of PCH that occurred within 12 months of each other. We quickly diagnosed the second case and treated the patient successfully, in part due to our recognition of its characteristics based on the first case. PCH is a hemolytic anemia for which there is a specific diagnostic test; the timely recognition of this entity by physicians and laboratory staff will allow prompt, supportive therapy and will raise the odds of quick resolution of hemolysis.

Pulmonary pathology of rapidly fatal transfusion-related acute lung injury reveals minimal evidence of diffuse alveolar damage or alveolar granulocyte infiltration.

BACKGROUND: Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-associated death in the United States. Its diagnosis is based on clinical and radiographic changes that are indistinguishable from acute lung injury/acute respiratory distress syndrome (ALI/ARDS). TRALI is presumed to be a form of ALI/ARDS; however, it differs in its triggering events and associated mortality. Two cases of rapidly fatal TRALI in which the postmortem pathology differed from that classically associated with ALI/ARDS are reported. CASE REPORT: Two men (aged 75 and 83 years) developed rapidly fatal TRALI after receiving single units of plasma for correction of elevated international normalized ratios. The donors were found to have white blood cell (WBC) antibodies that included specificities for WBC antigens expressed by the recipient (HLA Class I or Class II and/or HNA-3b [5a] antibody). Autopsy findings in both patients revealed bilateral pleural effusions and extensive patchy areas of alveoli filled with proteinaceous fluid. The pulmonary capillaries were congested with red blood cells and WBCs. Diffuse alveolar damage, including interstitial inflammation, intraalveolar granulocyte infiltration, and hyaline membrane formation, were not identified in either case. CONCLUSION: In both patients the clinical and radiographic findings were indicative of TRALI and indistinguishable from ALI/ARDS. However, diffuse alveolar damage, the classic autopsy finding in ARDS, was not identified, suggesting a different pathogenesis. Further studies are needed on the role of polymorphonuclear cells in the initiating events of TRALI that lead to ALI and the resulting breakdown of the permeability integrity of the alveolar walls.

David B. Pall, PhD (1914-2004).

In this edition of the Pioneers and Pathfinders Series, the contributions of David B. Pall, PhD, to transfusion medicine are discussed. With the aid of Dr Pall's unpublished personal history and assistance from family members and the company he founded, we are able to provide perspective to several remarkable scientific advances. For those of us in transfusion medicine, the discovery of the world's first leukoreduction filter prevails as his most significant invention. However, to the rest of the world, Dr Pall pioneered filtration with applications in aerospace, microelectronics, general industry, and most recently, contamination control. The almost 60-year-old Pall Corporation continues to preserve his legacy.

Multicomponent donor apheresis in the Americas.

Multicomponent donor apheresis utilizes apheresis technology to collect combinations of red blood cells, platelets and plasma units. The United States has embraced this technology to the greatest extent of the countries in the Americas. As whole blood and apheresis collection have increased, so have the donor deferrals based on potential exposure to infectious agents. However, hemoglobin/hematocrit deferrals still remain the largest upfront deferral for volunteer donors. As the technology is refined in future years, multicomponent donor apheresis may become the predominant method of collecting blood products from donors.

Volunteer donor apheresis.

Volunteer donor apheresis has evolved from early plasmapheresis procedures that collected single components into technically advanced multicomponent procedures that can produce combinations of red blood cells, platelets, and plasma units. Blood collection and utilization is increasing annually in the United States. The number of apheresis procedures is also increasing such that single donor platelet transfusions now exceed platelet concentrates from random donors. Donor qualifications for apheresis vary from those of whole blood. Depending on the procedure, the donor weight, donation interval, and platelet count must be taken into consideration. Adverse effects of apheresis are well known and fortunately occur in only a very small percentage of donors. The recruitment of volunteer donors is one of the most challenging aspects of a successful apheresis program. As multicomponent apheresis becomes more commonplace, it is important for collection centers to analyze the best methods to recruit and collect donors.