Results of clinical effectiveness of conventional versus Mirasol-treated Apheresis Platelets in Patients with Hypoproliferative Thrombocytopenia (MiPLATE) trial.

BACKGROUND: The Mirasol® Pathogen Reduction Technology System was developed to reduce transfusion-transmitted diseases in platelet (PLT) products. STUDY DESIGN AND METHODS: MiPLATE trial was a prospective, multicenter, controlled, randomized, non-inferiority (NI) study of the clinical effectiveness of conventional versus Mirasol-treated Apheresis PLTs in participants with hypoproliferative thrombocytopenia. The novel primary endpoint was days of ≥Grade 2 bleeding with an NI margin of 1.6. RESULTS: After 330 participants were randomized, a planned interim analysis of 297 participants (145 MIRASOL, 152 CONTROL) receiving ≥1 study transfusion found a 2.79-relative rate (RR) in the MIRASOL compared to the CONTROL in number of days with ≥Grade 2 bleeding (95% confidence interval [CI] 1.67-4.67). The proportion of subjects with ≥Grade 2 bleeding was 40.0% (n = 58) in MIRASOL and 30.3% (n = 46) in CONTROL (RR = 1.32, 95% CI 0.97-1.81, p = .08). Corrected count increments were lower (p < .01) and the number of PLT transfusion episodes per participant was higher (RR = 1.22, 95% CI 1.05-1.41) in MIRASOL. There was no difference in the days of PLT support (hazard ratio = 0.86, 95% CI 0.68-1.08) or total number of red blood cell transfusions (RR = 1.12, 95% CI 0.91-1.37) between MIRASOL versus CONTROL. Transfusion emergent adverse events were reported in 119 MIRASOL participants (84.4%) compared to 133 (82.6%) participants in CONTROL (p = NS). DISCUSSION: This study did not support that MIRASOL was non-inferior compared to conventional platelets using the novel endpoint number of days with ≥Grade 2 bleeding in MIRASOL when compared to CONTROL.

Confronting the challenge of gender nonconforming donors: A blood center's three-year experience.

BACKGROUND: Blood center organizations (BCOs) have traditionally offered two gender choices (male or female) on the donor history questionnaire (DHQ). Our BCO was one of the first in the United States to offer additional options on our DHQ to improve the experience for gender nonconforming donors. STUDY DESIGN AND METHODS: Three years of data were analyzed from all blood donation visits between March 2019 and March 2022. Donors were stratified by gender categories and generation as follows: Gen Z, Millennial, Gen X, Boomers, and Silent. First time donor status, donor deferrals and infectious disease rates were evaluated for each category. RESULTS: Donor gender makeup included 127,072 (99.78%) Male/Female (M/F) and 282 (0.22%) Trans/Other (T/O) donors. The return rate for first-time donors was 36.75% for M/F donors compared to 33.84% for T/O donors. The generational breakdown of our T/O donors is 71.28% Gen Z, 21.99% Millennial, 3.19% Gen X, 3.55% Boomers and none from the Silent Generation. Comparing high risk DHQ deferrals, there were 719 (0.57%) M/F deferrals and 18 (6.38%) T/O deferrals. Disease marker testing resulted in 2314 (0.56%) deferrals of M/F donors compared to 2 (0.41%) T/O deferrals. CONCLUSION: Increased gender options on the DHQ allowing gender diverse self-identification enhances inclusivity. Transgender and nonbinary individuals accounted for a minority of donors, most of whom are younger, and have a comparable return rate to M/F donors. Shifts in donor policies can ensure inclusivity of this diverse population and provide an opportunity to expand the base of eligible donors.

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.

Clinical Practice Guidelines From the Association for the Advancement of Blood and Biotherapies (AABB): COVID-19 Convalescent Plasma.

DESCRIPTION: Coronavirus disease 2019 convalescent plasma (CCP) has emerged as a potential treatment of COVID-19. However, meta-analysis data and recommendations are limited. The Association for the Advancement of Blood and Biotherapies (AABB) developed clinical practice guidelines for the appropriate use of CCP. METHODS: These guidelines are based on 2 living systematic reviews of randomized controlled trials (RCTs) evaluating CCP from 1 January 2019 to 26 January 2022. There were 33 RCTs assessing 21 916 participants. The results were summarized using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method. An expert panel reviewed the data using the GRADE framework to formulate recommendations. RECOMMENDATION 1 (OUTPATIENT): The AABB suggests CCP transfusion in addition to the usual standard of care for outpatients with COVID-19 who are at high risk for disease progression (weak recommendation, moderate-certainty evidence). RECOMMENDATION 2 (INPATIENT): The AABB recommends against CCP transfusion for unselected hospitalized persons with moderate or severe disease (strong recommendation, high-certainty evidence). This recommendation does not apply to immunosuppressed patients or those who lack antibodies against SARS-CoV-2. RECOMMENDATION 3 (INPATIENT): The AABB suggests CCP transfusion in addition to the usual standard of care for hospitalized patients with COVID-19 who do not have SARS-CoV-2 antibodies detected at admission (weak recommendation, low-certainty evidence). RECOMMENDATION 4 (INPATIENT): The AABB suggests CCP transfusion in addition to the usual standard of care for hospitalized patients with COVID-19 and preexisting immunosuppression (weak recommendation, low-certainty evidence). RECOMMENDATION 5 (PROPHYLAXIS): The AABB suggests against prophylactic CCP transfusion for uninfected persons with close contact exposure to a person with COVID-19 (weak recommendation, low-certainty evidence). GOOD CLINICAL PRACTICE STATEMENT: CCP is most effective when transfused with high neutralizing titers to infected patients early after symptom onset.

Ultrasensitive detection of salivary SARS-CoV-2 IgG antibodies in individuals with natural and COVID-19 vaccine-induced immunity.

We assessed the feasibility of a highly sensitive immunoassay method based on single molecule array (Simoa) technology to detect IgG and IgA antibodies against SARS-CoV-2 spike protein receptor binding domain (RBD) in saliva from individuals with natural or vaccine-induced COVID-19 immunity. The performance of the method was compared to a laboratory-developed SARS-CoV-2 RBD total antibody enzyme-linked immunosorbent assay (ELISA). Paired serum and saliva specimens were collected from individuals (n = 40) prior to and 2 weeks after receiving an initial prime COVID-19 vaccine dose (Pfizer/BioNTech BNT162b2 or Moderna mRNA-1273). Saliva was collected using a commercially available collection device (OraSure Inc.) and SARS-CoV-2 RBD IgG antibodies were measured by an indirect ELISA using concentrated saliva samples and a Simoa immunoassay using unconcentrated saliva samples. The IgG results were compared with paired serum specimens that were analyzed for total RBD antibodies using the ELISA method. The analytical sensitivity of the saliva-based Simoa immunoassay was five orders of magnitude higher than the ELISA assay: 0.24 pg/mL compared to 15 ng/mL. The diagnostic sensitivity of the saliva ELISA method was 90% (95% CI 76.3-97.2%) compared to 91.7% (95% CI 77.5-98.2%) for the Simoa immunoassay without total IgG-normalization and 100% (95% CI 90.3-100%) for the Simoa immunoassay after total IgG-normalization when compared to the serum ELISA assay. When analyzed using the SARS-CoV-2 RBD IgG antibody ELISA, the average relative increase in antibody index (AI) between the saliva of the post- and pre-vaccinated individuals was 8.7 (AIpost/pre). An average relative increase of 431 pg/mL was observed when the unconcentrated saliva specimens were analyzed using the Simoa immunoassay (SARS-CoV-2 RBD IgGpost/pre). These findings support the suitability of concentrated saliva specimens for the measurement of SARS-CoV-2 RBD IgG antibodies via ELISA, and unconcentrated saliva specimens for the measurement of SARS-CoV-2 RBD IgG and IgA using an ultrasensitive Simoa immunoassay.

Estimated US Infection- and Vaccine-Induced SARS-CoV-2 Seroprevalence Based on Blood Donations, July 2020-May 2021.

Importance: People who have been infected with or vaccinated against SARS-CoV-2 have reduced risk of subsequent infection, but the proportion of people in the US with SARS-CoV-2 antibodies from infection or vaccination is uncertain. Objective: To estimate trends in SARS-CoV-2 seroprevalence related to infection and vaccination in the US population. Design, Setting, and Participants: In a repeated cross-sectional study conducted each month during July 2020 through May 2021, 17 blood collection organizations with blood donations from all 50 US states; Washington, DC; and Puerto Rico were organized into 66 study-specific regions, representing a catchment of 74% of the US population. For each study region, specimens from a median of approximately 2000 blood donors were selected and tested each month; a total of 1 594 363 specimens were initially selected and tested. The final date of blood donation collection was May 31, 2021. Exposure: Calendar time. Main Outcomes and Measures: Proportion of persons with detectable SARS-CoV-2 spike and nucleocapsid antibodies. Seroprevalence was weighted for demographic differences between the blood donor sample and general population. Infection-induced seroprevalence was defined as the prevalence of the population with both spike and nucleocapsid antibodies. Combined infection- and vaccination-induced seroprevalence was defined as the prevalence of the population with spike antibodies. The seroprevalence estimates were compared with cumulative COVID-19 case report incidence rates. Results: Among 1 443 519 specimens included, 733 052 (50.8%) were from women, 174 842 (12.1%) were from persons aged 16 to 29 years, 292 258 (20.2%) were from persons aged 65 years and older, 36 654 (2.5%) were from non-Hispanic Black persons, and 88 773 (6.1%) were from Hispanic persons. The overall infection-induced SARS-CoV-2 seroprevalence estimate increased from 3.5% (95% CI, 3.2%-3.8%) in July 2020 to 20.2% (95% CI, 19.9%-20.6%) in May 2021; the combined infection- and vaccination-induced seroprevalence estimate in May 2021 was 83.3% (95% CI, 82.9%-83.7%). By May 2021, 2.1 SARS-CoV-2 infections (95% CI, 2.0-2.1) per reported COVID-19 case were estimated to have occurred. Conclusions and Relevance: Based on a sample of blood donations in the US from July 2020 through May 2021, vaccine- and infection-induced SARS-CoV-2 seroprevalence increased over time and varied by age, race and ethnicity, and geographic region. Despite weighting to adjust for demographic differences, these findings from a national sample of blood donors may not be representative of the entire US population.

Detection of Babesia RNA and DNA in whole blood samples from US blood donations.

BACKGROUND: Human babesiosis is a zoonotic infection caused by an intraerythrocytic parasite. The highest incidence of babesiosis is in the United States, although cases have been reported in other parts of the world. Due to concerns of transfusion-transmitted babesiosis, the US Food and Drug Administration (FDA) recommended year-round regional testing for Babesia by nucleic acid testing or use of an FDA-approved device for pathogen reduction. A new molecular test, cobas Babesia (Roche Molecular Systems, Inc.), was evaluated for the detection of the four species that cause human disease, Babesia microti, Babesia duncani, Babesia divergens, and Babesia venatorum. STUDY DESIGN AND METHODS: Analytical performance was evaluated followed by clinical studies on whole blood samples from US blood donations collected in a special tube containing a chaotropic reagent that lyses the red cells and preserves nucleic acid. Sensitivity and specificity of the test in individual samples (individual donation testing [IDT]) and in pools of six donations were determined. RESULTS: Based on analytical studies, the claimed limit of detection of cobas Babesia for B. microti is 6.1 infected red blood cells (iRBC)/mL (95% confidence interval [CI]: 5.0, 7.9); B. duncani was 50.2 iRBC/mL (95% CI: 44.2, 58.8); B. divergens was 26.1 (95% CI: 22.3, 31.8); and B. venatorum was 40.0 iRBC/mL (95% CI: 34.1, 48.7). The clinical specificity for IDT was 99.999% (95% CI: 99.996, 100) and 100% (95% CI: 99.987, 100) for pools of six donations. CONCLUSION: cobas Babesia enables donor screening for Babesia species with high sensitivity and specificity.

The effect of the SARS-CoV-2 pandemic and civil unrest on massive transfusion protocol activations in Minneapolis 2020.

BACKGROUND: The year 2020 presented the transfusion community with unprecedented events and challenges, including the ongoing SARS-CoV-2 (COVID-19) pandemic, and more recently by civil unrest, following the death of George Floyd in late May of 2020. As a level 1 trauma center located in Minneapolis, Minnesota, Hennepin Healthcare (HCMC) offers a unique perspective into the changes in massive transfusion protocol (MTP) activations and usage during this tumultuous period. This may provide insight for addressing similar future events. STUDY DESIGN AND METHODS: MTP logs from March 2020 to August 2020 were compared to logs from March to August 2019. The data were de-identified, and MTP activations and component usage were categorized by activation reason. These categories were compared across the 2-year period to examine the impact of COVID-19, including stay-at-home orders, and civil unrest. RESULTS: For the examined 6 months of the year 2020, there were a total of 140 MTP activations, compared to 143 in 2019. There were more activations for violent trauma (VT) in 2020 than 2019 (44 vs. 32). This increase in activations for VT was offset by a decrease in non-trauma activations (54 vs. 66). There was a significant increase in the number of components used in VT activations. DISCUSSION: During 2020, the initial mild decrease in MTP activations was followed by a dramatic increase in the number of activations and component usage for VT in June and July of that year.

Pediatric resident knowledge of transfusion medicine: Results from the BEST-TEST3 international education needs assessment.

BACKGROUND: Transfusions are a common intervention within pediatrics and require unique considerations to optimize patient care. Poor knowledge of evidence-based transfusion practice can lead to misuse of transfusion therapy and harm. While there have been assessments of transfusion medicine knowledge of physicians caring for adult patients, there is little data regarding pediatricians. STUDY DESIGN AND METHODS: Using a published transfusion medicine knowledge exam for internal medicine physicians as a backbone, pediatric transfusion medicine experts, using an iterative process, developed a pediatric-specific examination. Pilot testing and Rasch analysis, a method used in high-stakes testing, was used to validate the exam. The exam and a previously validated survey on transfusion medicine training, attitudes, and perceived ability were administered to pediatric residents. Analysis consisted of descriptive statistics as well as comparisons of exam scores based on survey responses. RESULTS: 330 pediatric residents from 19 sites in 6 countries participated in the study. The vast majority (91%) of residents had obtained blood product consent. The mean exam score was 37.1% (range 9.5%-71.4%) with no statistical differences based on amount or perceived quality of transfusion medicine education or perceived ability. DISCUSSION: A rigorously validated exam has now been developed that can be used to assess pediatric transfusion medicine knowledge. A large international group of pediatric residents performed poorly on the exam demonstrating a pressing need for improved transfusion medicine education to ensure safe and appropriate administration of blood components to infants and children.

A case study of 10 patients administered HBOC-201 in high doses over a prolonged period: outcomes during severe anemia when transfusion is not an option.

BACKGROUND: Hemoglobin-Based Oxygen Carriers (HBOCs) can act as an "oxygen bridge" in acute severe anemia when transfusion is indicated, but not possible. We present data on 10 Expanded Access (EA) patients treated with high cumulative doses of Hemopure (HBOC-201), to assess the ability of HBOC-201 to safely treat life threatening anemia in situations where high volumes of product were administered over an extended period of time. STUDY DESIGN AND METHODS: Inclusion in this study required that the patient receive at least 10 units of HBOC-201 between 2014 and 2017 under the FDA-sanctioned EA program. Depending on a patient's geographical location, treatment with HBOC-201 was obtained through either a single patient emergency Investigational New Drug (IND) application, or an intermediate size population IND. Of the 41 patients who were treated during this period, 10 patients received 10 or more units of the product. Data were obtained from medical records. RESULTS: Treatments with HBOC-201 started within 24 hours of signing consent and were administered at an average rate of 1.99 (SD 0.17) units per day over a mean of 8.2 days (SD 2.9), during which patients received on average 16.2 units (SD 5.7 units) of HBOC-201. The median pre-treatment nadir corpuscular hemoglobin (Hb) concentration was 3.3 (SD 0.9) g/dL and post-treatment Hemoglobin was 7.3 (SD 1.7) g/dL. Common side effects included methemoglobinemia, gastrointestinal symptoms, and hypertension. However, no product-related serious adverse events (SAEs) were noted. All patients survived. CONCLUSIONS: Administration of HBOC-201 over an extended period is a feasible and safe oxygen bridge for severely anemic patients who cannot be transfused with RBC.

Therapeutic Phlebotomy for Testosterone-Induced Polycythemia.

OBJECTIVES: To evaluate therapeutic phlebotomy (TP) requests for testosterone replacement therapy (TRT) and to highlight the impact to a blood center (BC) or service that provides TP for individuals on TRT. METHODS: Review of TP requests for individuals on TRT at our BC over a 3-year period from 2014 through 2016, as well as the total number of TP collections. RESULTS: Total TPs during 2014, 2015, and 2016 were 475, 500, and 569, respectively. Annual TP collections for patients on TRT were 193, 212, and 239, respectively. TRT patients with TP orders increased 71.4% during this period. After discontinuation of TP services for TRT at our BC, 32% continued to donate as volunteer blood donors at our BC. CONCLUSIONS: Our BC observed increased TP requests for patients on TRT from 2014 through 2016. Our findings suggest that individuals on TRT may be presenting to BCs as volunteer blood donors to avoid charges for TP.

Variations in hemoglobin measurement and eligibility criteria across blood donation services are associated with differing low-hemoglobin deferral rates: a BEST Collaborative study.

BACKGROUND: Determination of blood donor hemoglobin (Hb) levels is a pre-requisite to ensure donor safety and blood product quality. We aimed to identify Hb measurement practices across blood donation services and to what extent differences associate with low-Hb deferral rates. METHODS: An online survey was performed among Biomedical Excellence for Safer Transfusion (BEST) Collaborative members, extended with published data. Multivariable negative-binomial regression models were built to estimate adjusted associations of minimum donation intervals, Hb cut-offs (high, ≥13.5 g/dL in men or ≥ 12.5 g/dL in women, vs. lower values), iron monitoring (yes/no), providing or prescribing iron supplementation (yes/no), post-versus pre-donation Hb measurement and geographical location (Asian vs. rest), with low-Hb deferral rates. RESULTS: Data were included from 38 blood services. Low-Hb deferral rates varied from 0.11% to 8.81% among men and 0.84% to 31.85% among women. Services with longer minimum donation intervals had significantly lower deferral rates among both women (rate ratio, RR 0.53, 95%CI 0.33-0.84) and men (RR 0.53, 95%CI 0.31-0.90). In women, iron supplementation was associated with lower Hb deferral rates (RR 0.47, 95%CI 0.23-0.94). Finally, being located in Asia was associated with higher low-Hb deferral rates; RR 9.10 (95%CI 3.89-21.27) for women and 6.76 (95%CI 2.45-18.68) for men. CONCLUSION: Differences in Hb measurement and eligibility criteria, particularly longer donation intervals and iron supplementation in women, are associated with variations in low-Hb deferral rates. These insights could help improve both blood donation service efficiency and donor care.

How do I incorporate red cell genotyping to improve chronic transfusion therapy?

BACKGROUND: Children with transfusion dependent anemia, such as sickle cell disease (SCD) and thalassemia, are at an increased risk for developing red blood cell (RBC) alloantibodies due to their lifelong need for transfusion therapy. With the advent of genotyping, extended RBC antigen typing can be incorporated into chronic transfusion therapy programs (CTTPs) to improve patient care and provide antigen matched blood for this population of patients. STUDY DESIGN AND METHODS: The hospital, blood center (BC), and hematology clinic caring for children requiring long-term transfusion support developed a CTTP. Genotyping was performed at entry to determine patient RBC antigen type. Limited versus extended antigen matching of transfusions was provided based on known RBC antibodies. RESULTS: Fifty patients with the following disorders were enrolled: 20 with SCD, 23 with thalassemia, and 7 with other disorders. At enrollment, nine (18%) had RBC alloantibodies, including six (30%) of patients with SCD and three (13%) with thalassemia. Two children developed antibodies after enrollment; one warm autoantibody following limited "CEK" matched RBCs and one patient with a hemizygous variant RHD allele developed anti-D. Six (30%) patients with SCD had variant RHCE alleles; two had homozygous variant alleles and four had a variant present along with a wild type allele. CONCLUSION: We demonstrate how a CTTP can be developed in a community hospital through collaboration with the blood supplier, hospital, and clinical care team. A model of incorporating RBC genotyping informs risk for alloimmunization and allows consideration of transfusion strategy for providing prophylactic antigen matched blood.