Transfusion of ABO-group identical red blood cells following uncrossmatched transfusion does not lead to higher mortality in civilian trauma patients.

BACKGROUND: Questions persist about the safety of switching non-group O recipients of group O uncrossmatched red blood cells (RBC) or low titer group O whole blood (LTOWB) to ABO-identical RBCs during their resuscitation. METHODS: The database of an earlier nine-center study of transfusing incompatible plasma to trauma patients was reanalyzed. The patients were divided into three groups based on 24-h RBC transfusion: (1) group O patients who received group O RBC/LTOWB units (control group, n = 1203), (2) non-group O recipients who received only group O units (n = 646), (3) non-group O recipients who received at least one unit of group O and non-group O units (n = 562). Fixed marginal effect of receipt of non-O RBC units on 6- and 24-h and 30-day mortality was calculated. RESULTS: The non-O patients who received only group O RBCs received fewer RBC/LTOWB units and had slightly but significantly lower injury severity score compared to control group; non-group O patients who received both group O and non-O units received significantly more RBC/LTOWB units and had a slightly but significantly higher injury severity score compared to control group. In the multivariate analysis, the non-O patients who received only group O RBCs had significantly higher mortality at 6-h compared to the controls; the non-group O recipients of O and non-O RBCs did not demonstrate higher mortality. At 24-h and 30-days, there were no differences in survival between the groups. CONCLUSION: Providing non-group O RBCs to non-group O trauma patients who also received group O RBC units is not associated with higher mortality.

Management and Follow-up of Massive Fetomaternal Hemorrhage Requiring High-Dose Rh Immune Globulin: A Case Report.

OBJECTIVES: Massive fetomaternal hemorrhage (FMH) is rare and reported to be the cause in approximately 3% of all fetal deaths. Maternal management of massive FMH includes prevention of Rh(D) alloimmunization in Rh(D)-negative mothers by administration of Rh(D) immune globulin (RhIG). METHODS: We describe a case of a 30-year-old O-negative, primigravida woman who presented at 38 weeks of gestation with decreased fetal movements. She underwent an emergency cesarean section and delivered an O-positive baby girl who died shortly after birth. RESULTS: The patient's FMH screen was positive, with a Kleihauer-Betke test demonstrating 10.7% fetal blood in maternal circulation. The calculated dose of 6,300 µg RhIG was given prior to discharge over 2 days using an intravenous (IV) preparation. Antibody screening a week after discharge showed anti-D and anti-C. The anti-C was attributed to acquired passive immunity from the large dose of RhIG. Anti-C reactivity waned and was negative at 6 months, but the anti-D pattern persisted at 9 months postdelivery. Negative antibody screens were noted at 12 and 14 months. CONCLUSIONS: This case highlights the immunohematology challenges of IV RhIG as well as the success in preventing alloimmunization with IV RhIG given the patient's complete resolution of anti-C and no anti-D formation, with a subsequent healthy pregnancy.

Serologic reactivity of unidentified specificity in antenatal testing and hemolytic disease of the fetus and newborn: The BEST collaborative study.

BACKGROUND: The clinical significance of serologic reactivity of unidentified specificity (SRUS) in pregnancy is not clear based on available literature. The aim of this study is to determine if SRUS is associated with hemolytic disease of the fetus and newborn (HDFN). STUDY DESIGN AND METHODS: Retrospective data were collected from eight institutions over an 11-year study period (2010-2020), when available (5/8 sites). The outcome of the pregnancies with SRUS-no, mild, moderate, or severe HDFN-was determined. RESULTS: SRUS was demonstrated in 589 pregnancies. After excluding those with incomplete data, a total of 284 pregnancies were included in the primary HDFN outcome analysis. SRUS was detected in 124 (44%) pregnancies in isolation, and none were affected by HDFN. Of 41 pregnancies with SRUS and ABO incompatibility, 37 (90%) were unaffected, and 4 (10%) were associated with mild HDFN. Of 98 pregnancies with SRUS and concurrent identifiable antibody reactivity(s), 80 (81%) were unaffected, and 19 (19%) were associated with mild to severe HDFN. There was 1 case of mild HDFN and 1 case of severe HDFN in the 21 pregnancies with SRUS, ABO incompatibility, and concurrent identifiable antibody reactivity(s), and 19 (90%) were unaffected by HDFN. Among all patients with repeat testing, newly identified alloantibodies or other antibodies were identified in 63 of 212 (30%) patients. Although most were not clinically significant, on occasion SRUS preceded clinically significant antibody(s) associated with HDFN (3%, 5/188). CONCLUSION: The antenatal serologic finding of SRUS in isolation is not associated with HDFN but may precede clinically significant antibodies.

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.

Hospital red blood cell and platelet supply and utilization from March to December of the first year of the COVID-19 pandemic: The BEST collaborative study.

BACKGROUND: At the start of the coronavirus disease 2019 (COVID-19) pandemic, widespread blood shortages were anticipated. We sought to determine how hospital blood supply and blood utilization were affected by the first wave of COVID-19. STUDY DESIGN AND METHODS: Weekly red blood cell (RBC) and platelet (PLT) inventory, transfusion, and outdate data were collected from 13 institutions in the United States, Brazil, Canada, and Denmark from March 1st to December 31st of 2020 and 2019. Data from the sites were aligned based on each site's local first peak of COVID-19 cases, and data from 2020 (pandemic year) were compared with data from the corresponding period in 2019 (pre-pandemic baseline). RESULTS: RBC inventories were 3% lower in 2020 than in 2019 (680 vs. 704, p < .001) and 5% fewer RBCs were transfused per week compared to 2019 (477 vs. 501, p < .001). However, during the first COVID-19 peak, RBC and PLT inventories were higher than normal, as reflected by deviation from par, days on hand, and percent outdated. At this time, 16% fewer inpatient beds were occupied, and 43% fewer surgeries were performed compared to 2019 (p < .001). In contrast to 2019 when there was no correlation, there was, in 2020, significant negative correlations between RBC and PLT days on hand and both percentage occupancy of inpatient beds and percentage of surgeries performed. CONCLUSION: During the COVID-19 pandemic in 2020, RBC and PLT inventories remained adequate. During the first wave of cases, significant decreases in patient care activities were associated with excess RBC and PLT supplies and increased product outdating.

Logistics of managing a trauma whole blood inventory in a civilian level 1 trauma center.

BACKGROUND: Institutional data on initiating and maintaining a low-titer O positive whole blood (LTOWB) inventory for the civilian trauma sector may help other institutions start a LTOWB program. This study from a level 1 trauma center with a hospital-based donor center highlights challenges faced during the collection, maintenance, and utilization of LTOWB. STUDY DESIGN AND METHODS: Male O positive donors with low (≤1:100) anti-A and anti-B antibody titers were recruited for LTOWB collection. The daily inventory goal of 4 LTOWB units was kept in the emergency department refrigerator and transfused to adult male trauma patients. Unused units older than 10 days were reprocessed into packed red blood cells. RESULTS: Of 900 donors screened, 61% qualified and 52% of eligible donors provided a collective total of 505 LTOWB units over 2.5 years. The number of collected units directly correlated with the availability of inventory; 42% of the units were transfused, 54% were reprocessed, and 4% were discarded. The inventory goal was maintained for 56% of the year 2018 and 83% of the year 2019. Over these 2 years, 52% of patients had their transfusion needs fully met, 41% had their needs partially met, and 6.5% did not have their needs met. DISCUSSION: Initial challenges to LTOWB implementation were inventory shortages, low utilization rates, and failure to meet clinical demand. Proposed solutions include allowing for a higher yet safe titer, extending shelf life, expanding the donor pool, identifying barriers to utilization, and permitting use in female trauma patients beyond childbearing age.

Rate of D-alloimmunization in trauma does not depend on the number of RhD-positive units transfused: The BEST collaborative study.

BACKGROUND: Evidence indicates the life-saving benefits of early blood product transfusion in severe trauma resuscitation. Many of these products will be RhD-positive, so understanding the D-alloimmunization rate is important. METHODS: This was a multicenter, retrospective study whereby injured RhD-negative patients between 18-50 years of age who received at least one unit of RhD-positive red blood cells (RBC) or low titer group O whole blood (LTOWB) during their resuscitation between 1 January, 2010 through 31 December, 2019 were identified. If an antibody detection test was performed ≥14 days after the index RhD-positive transfusion then basic demographic information was collected, including whether the patient became D-alloimmunized. The overall D-alloimmunization rate, and the rate stratified by the number of units transfused, were calculated. RESULTS: Data were collected from nine institutions. Five institutions reported fewer than 10 eligible patients each and were excluded. From the remaining four institutions, all from the USA, there were 235 eligible patients; 77 (random effects estimate: 32.7%; 95% CI: 19.1-50.1%) became D-alloimmunized. Three of the institutions reported D-alloimmunization rates ≥38.6%, while the remaining institution's rate was 12.2%. In both random and fixed-effects models, the rate of D-alloimmunization was not significantly different between those who received one RhD-positive unit and those who received multiple RhD-positive units. CONCLUSION: In this large, multicenter study of injured patients, the overall rate of D-alloimmunization fell within the range previously reported. The rate of D-alloimmunization did not increase as the number of transfused RhD-positive units increased. These data can help to inform RhD type selection decisions.

Displaying Cost and Completion Time for Reference Laboratory Test Orders-A Randomized Controlled Trial.

OBJECTIVES: Reduction in unnecessary services is one strategy for increasing the value of health care. Reference laboratory, or send-out, tests are associated with considerable costs. We investigated whether displaying cost and turnaround time (TAT), or time-to-result, for reference laboratory tests at the time of order entry in the electronic health record (EHR) system would impact provider ordering practices. METHODS: Reference laboratory test cost and TAT data were randomized prior to the study and only displayed for the intervention group. A 24-month dataset composed of 12 months each for baseline and study periods was extracted from the clinical data mart. A difference-in-differences (DID) analysis was conducted using a linear mixed-effects model to estimate the association between the intervention and changes in test-ordering patterns. RESULTS: In the inpatient setting, the DIDs of aggregate test-order costs and volume were not different among the control and intervention groups (p = 0.31 and p = 0.26, respectively). In the ambulatory setting, the DIDs of aggregate test-order costs and volume were not different among the control and intervention groups (p = 0.82 and p = 0.51, respectively). For both inpatient and ambulatory settings, no significant difference was observed in the DID of aggregate test-order costs and volumes calculated in respect to stratified relative cost and TAT groups (p > 0.05). CONCLUSION: Lack of alternative tests, test orders placed at a late step in patient management, and orders facilitated by trainees or mid-level providers may have limited the efficacy of the intervention. Our randomized study demonstrated no significant association between the display of cost or TAT display and ordering frequency.

Blood donor eligibility criteria for medical conditions: A BEST collaborative study.

BACKGROUND AND OBJECTIVES: Donor eligibility questions and criteria for medical conditions vary between blood centres, suggesting that they are based more on local regulations or experience, rather than on published data, which are limited. As the donor population ages, medical conditions become more common. We assessed donor health assessment criteria at blood centre members of the Biomedical Excellence for Safer Transfusion (BEST) Collaborative. Our aim was to compare eligibility criteria and determine their underlying basis. MATERIALS AND METHODS: A REDCap survey was sent to blood centre participants, based on medical conditions of greatest interest suggested by the Donor Studies Team of the BEST Collaborative. Participants were asked about current donor health assessment questions, deferral criteria and the basis for their deferral policy (donor risk, recipient risk or both) for 20 medical conditions. RESULTS: Complete responses were received from 26 blood donor centres (24 separate responses) representing a combination of hospital-based centres, large regional centres and community/national blood centres in 14 different countries. Most centres specifically ask about heart and lung conditions, whereas fewer than half inquire about kidney, gastrointestinal or neurological conditions. North American blood centres tended to be less restrictive, while regulatory restrictions are more prevalent in Europe. Most participants felt that the criteria were based on regulatory requirements or experience, rather than on published data. CONCLUSION: There is considerable variability in criteria by region. Ideally, criteria would be more evidence-based rather than based on regulatory requirements or experience. Deferral criteria must balance donor and recipient safety and maintain an adequate blood supply.

How do I implement an outpatient program for the administration of convalescent plasma for COVID-19?

Convalescent plasma, collected from donors who have recovered from a pathogen of interest, has been used to treat infectious diseases, particularly in times of outbreak, when alternative therapies were unavailable. The COVID-19 pandemic revived interest in the use of convalescent plasma. Large observational studies and clinical trials that were executed during the pandemic provided insight into how to use convalescent plasma, whereby high levels of antibodies against the pathogen of interest and administration early within the time course of the disease are critical for optimal therapeutic effect. Several studies have shown outpatient administration of COVID-19 convalescent plasma (CCP) to be both safe and effective, preventing clinical progression in patients when administered within the first week of COVID-19. The United States Food and Drug Administration expanded its emergency use authorization (EUA) to allow for the administration of CCP in an outpatient setting in December 2021, at least for immunocompromised patients or those on immunosuppressive therapy. Outpatient transfusion of CCP and infusion of monoclonal antibody therapies for a highly transmissible infectious disease introduces nuanced challenges related to infection prevention. Drawing on our experiences with the clinical and research use of CCP, we describe the logistical considerations and workflow spanning procurement of qualified products, infrastructure, staffing, transfusion, and associated management of adverse events. The purpose of this description is to facilitate the efforts of others intent on establishing outpatient transfusion programs for CCP and other antibody-based therapies.

Antibody profiles in COVID-19 convalescent plasma prepared with amotosalen/UVA pathogen reduction treatment.

BACKGROUND: COVID-19 convalescent plasma (CCP), from donors recovered from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, is one of the limited therapeutic options currently available for the treatment of critically ill patients with COVID-19. There is growing evidence that CCP may reduce viral loads and disease severity; and reduce mortality. However, concerns about the risk of transfusion-transmitted infections (TTI) and other complications associated with transfusion of plasma, remain. Amotosalen/UVA pathogen reduction treatment (A/UVA-PRT) of plasma offers a mitigation of TTI risk, and when combined with pooling has the potential to increase the diversity of the polyclonal SARS-CoV-2 neutralizing antibodies. STUDY DESIGN AND METHODS: This study assessed the impact of A/UVA-PRT on SARS-CoV-2 antibodies in 42 CCP using multiple complimentary assays including antigen binding, neutralizing, and epitope microarrays. Other mediators of CCP efficacy were also assessed. RESULTS: A/UVA-PRT did not negatively impact antibodies to SARS-CoV-2 and other viral epitopes, had no impact on neutralizing activity or other potential mediators of CCP efficacy. Finally, immune cross-reactivity with other coronavirus antigens was observed raising the potential for neutralizing activity against other emergent coronaviruses. CONCLUSION: The findings of this study support the selection of effective CCP combined with the use of A/UVA-PRT in the production of CCP for patients with COVID-19.

Who donates? Patterns of blood donation and donor characteristics at a university-affiliated hospital-based donor center.

BACKGROUND: Blood donors are a crucial element of the blood supply chain. Optimal recruitment strategies built upon the robust understanding of local donor behavior and demographics-specifically, the donor characteristics of our university-affiliated hospital-based donor center-improve outreach and retention of donors. STUDY DESIGN AND METHODS: This retrospective study analyzed blood donors' genders, ethnicities, and donation frequencies at a university-affiliated hospital-based donor center from 2014-2019, stratified into seven age cohorts. Donor ethnicity demographics were compared to the reported student, employee, and LA County population. RESULTS: Female donors outnumbered male donors in all age cohorts. The majority of donors self-identified (SI) as White (36.7%), Hispanic/Latino (21.6%), or Asian (19.1%). Older donors (age > 25) donated more frequently (4.1 vs. 2.3 donations per donor) than younger donors (age ≤ 25). Repeat donors who donated in multiple years during the study period were more likely to donate multiple times each year than those donors who only donated during 1 year. DISCUSSION: Our donor demographics more closely reflect the university student and employee demographics than LA County demographics, demonstrating the broad local efforts of recruitment by student groups and donor center recruitment staff. However, non-White populations continue to be underrepresented. The majority of donors only donated once during the study period. Recruitment strategies to increase donor engagement among underrepresented populations and increase the proportion of repeat donors are likely to prove most beneficial.

IgM Warm Autoantibodies Causing Autoimmune Hemolytic Anemia in a Pediatric Patient.

Most often, IgM-mediated autoimmune hemolytic anemia (AIHA) presents as cold agglutinin disease in the pediatric population. The IgM warm agglutinins are rare, with few reports in the literature. This case study describes a 5 year old girl with nausea, abdominal pain and jaundice, and a hemoglobin of 5.5 g/dL who was diagnosed with a warm reactive IgM AIHA. The laboratory workup revealed a pan-reactive antibody and a direct antiglobulin test negative for IgG and C3. A thermal amplitude assay revealed reactive IgM antibodies at 37°C, 30°C, 25°C, and 4°C and an antibody titer of 1:8. An adsorption for IgM-specific autoantibodies exposed underlying anti-E and anti-Cw alloantibodies. Transfusion of phenotypically matched red blood cell units supported ongoing hemolysis. The AIHA treatment included steroids followed by rituximab with complete resolution. A literature review shows variable outcomes for warm AIHA in the pediatric population and often describes the presence of warm reactive IgM-mediated AIHA as an indicator for poor prognosis.

To Reflex or Not to Reflex: A Time and Cost-Effectiveness Analysis of Autocontrol with Reflex DAT versus Direct DAT.

OBJECTIVE: Performing autocontrol with a reflex direct antiglobulin test (DAT) or directly performing IgG DAT only for alloantibody detection has been a matter of institutional preference. The aim of this study is to evaluate antibody identification (ABID), local cost, and staff time savings of both processes. METHODS: We retrospectively reviewed all positive indirect antiglobulin tests with corresponding ABID, DAT, autocontrol, and patients with newly identified antibodies in 2014 and 2016. The number of tests performed, ABID, and the cost differences between methods were compared. Cost analysis was estimated from direct material costs, labor costs, and time spent per ABID workup. RESULTS: Annual costs and time saved by performing direct IgG DAT only were $8460 and 180 hours, respectively. The percentage of new ABID in 2014 and 2016 was identical (3.3%). CONCLUSION: Removing autocontrol with reflex DATs at our center reduced costs and staff time while maintaining a comparable rate of positivity of ABID.

Educational cost-effective intervention to reduce pathologist's peripheral blood smears reviews with non-contributory findings: an academic institution experience.

Peripheral blood smear (PBS) review by a pathologist is a necessary and invaluable diagnostic tool. However, innovative highly sophisticated haematology analysers that flag peripheral blood abnormalities have decreased the need for a PBS review. Ordering practices including PBS reviews lumped as part of an 'order set' or with complete blood count (CBC) constituted most PBS requests at our institution. A retrospective review of all PBS review orders from 1 April 2016 to 31 January 2017 was performed to investigate the ordering practices at our institution. A total of 2864 PBS were ordered during the above study period. In many cases, the PBS report did not add any significant clinical information beyond that acquired by the CBC and differential count. These findings inspired policy changes within our institution for pathologist PBS reviews. Within the electronic order system, all PBS orders for inpatients were linked to a pop-up window with criteria for peripheral smear review and instructions on the approval policy. Outpatient orders required clinicians to request pathology approval. This implementation reduced total number of PBS orders by 42.5% with no adverse effect on patient management. Empowering pathologists and clinicians with guidelines on PBS review orders is a beneficial educational exercise of resource utilisation. Discussion with physicians regarding clinical indications reduces non-contributory PBS reviews, provides guidance to appropriate testing, and aptly allocates pathologist and laboratory staff time and resources.