The safety of COVID-19 convalescent plasma donation: A multi-institutional donor hemovigilance study.

BACKGROUND: Although the safety and therapeutic efficacy of COVID-19 convalescent plasma (CCP) has been extensively evaluated, the safety of CCP donation has not been explored in a multi-institutional context. STUDY DESIGN AND METHODS: Nine blood collection organizations (BCOs) participated in a multi-institutional donor hemovigilance effort to assess the safety of CCP donation. Donor adverse events (DAEs) were defined according to the Standard for Surveillance of Complications Related to Blood Donation, and severity was assessed using the severity grading tool. Multivariate analysis was performed to determine attributes associated with DAE severity. RESULTS: The overall DAE rate was 37.7 per 1000 donations. Repeat apheresis and apheresis-naïve donors experienced adverse event rates of 19.9 and 49.8 per 1000 donations, respectively. Female donors contributed 51.9% of CCP donations with a DAE rate of 49.4 per 1000 donations. The DAE rate for male donors was 27.4 per 1000 donations. Vasovagal reactions accounted for over half of all reported DAEs (51.1%). After adjustment, volume of CCP donated was associated with vasovagal reaction severity (odds ratio [OR] 6.5, 95% confidence interval [CI] 2.5-17.1). Donor age and donation history were also associated with DAE severity. Considerable differences in DAE types and rates were observed across the participating BCOs despite the use of standardized hemovigilance definitions. CONCLUSION: The safety of CCP donation appears comparable to that of conventional apheresis plasma donation with similar associated risk factors for DAE types and severity.

Apheresis technology correlates with bacterial contamination of platelets and reported septic transfusion reactions.

BACKGROUND: Apheresis technology to collect platelet (PLT) components differs among devices. We evaluated the relationship of the plateletpheresis device with bacterial contamination and reported septic transfusion reactions. STUDY DESIGN AND METHODS: Plateletpheresis was performed using Amicus (Fenwal, a Fresenius Kabi Company) or Trima (Trima Accel, TerumoBCT) from 2010 to 2014. All donations used inlet-line sample diversion and were tested by quality control (QC; Day 1) aerobic culture. Rates of bacterial contamination and septic reactions to PLTs were calculated for both devices. RESULTS: During the 5-year study period, plateletpheresis collections using Amicus and Trima devices totaled 1,486,888 and 671,955 donations, respectively. The rate of confirmed-positive bacterial cultures of apheresis PLT donations was significantly higher with Amicus than with Trima (252 vs. 112 per 106 donations [odds ratio {OR}, 2.3; 95% confidence interval {CI}, 1.8-2.9]). Septic transfusion reactions were caused by 30 apheresis PLT units from 25 contaminated Amicus procedures and three apheresis PLT units from three contaminated Trima procedures. The overall rate of septic reactions was significantly higher with apheresis PLT components collected with Amicus than with Trima (16.8 vs. 4.5 per 106 donations [OR, 3.8; 95% CI, 1.1-12.5]). All apheresis PLT components implicated in septic transfusion reactions had negative QC culture results incubated through Day 5 (i.e., false negatives). CONCLUSION: Apheresis technology affects bacterial contamination of plateletpheresis collections. The device-specific, higher rate of confirmed-positive bacterial culture results also correlated with a significantly higher rate of reported septic transfusion reactions to apheresis PLTs.

Predicted effect of selectively testing female donors for HLA antibodies to mitigate transfusion-related acute lung injury risk from apheresis platelets.

BACKGROUND: The use of male-donor-predominant plasma has reduced the risk of transfusion-related acute lung injury (TRALI), but the possible benefit of different mitigation strategies for other components is unknown. We evaluated the risk of TRALI from apheresis platelets (PLTs) to predict the effect of selectively testing female plateletpheresis donors who have been pregnant for HLA antibodies. STUDY DESIGN AND METHODS: The American Red Cross hemovigilance program classified TRALI cases from apheresis PLTs or red blood cells (RBCs) in 2006 to 2013 or from predominantly male-donor (>95%) plasma in 2008 to 2013 and compared the component-specific TRALI rates. RESULTS: The overall rate of TRALI was significantly higher for apheresis PLTs (6.2 cases per 10(6) units; OR [95% CI], 3.3 [2.3-4.8]) or plasma (3.8 cases per 10(6) units; OR [95% CI], 2.0 [1.4-2.9]) compared to RBCs (1.9 per 10(6) units). Twenty-nine of the 41 apheresis PLT cases involved female donors; 28 had been pregnant, and one had not been pregnant and was not tested. Twenty-five (61%) of the apheresis PLT TRALI cases had female donors with HLA Class I or Class II antibodies. In five of six cases that implicated specific HNA antibodies, the female parous donors also had multiple HLA antibodies. CONCLUSIONS: TRALI was more likely after transfusion of apheresis PLTs than male-donor-predominant plasma or RBCs. A selective strategy to test all female plateletpheresis donors who have been pregnant for HLA antibodies might reduce the risk of TRALI by approximately 60% and prevent some cases from coexisting HNA antibodies.

Clostridium perfringens in apheresis platelets: an unusual contaminant underscores the importance of clinical vigilance for septic transfusion reactions (CME).

BACKGROUND: Posttransfusion sepsis is typically caused by aerobic bacteria in apheresis platelets (PLTs) that escape detection by routine quality control cultures performed on every donation before components are distributed. We report the first case to implicate an anaerobic isolate, Clostridium perfringens, in apheresis PLTs and investigate its detection in vitro by approved tests. STUDY DESIGN AND METHODS: The C. perfringens strain was inoculated at high (10-100 colony-forming units [CFUs]/mL) or low (1-10 CFUs/mL) concentrations into apheresis PLTs and evaluated for growth over 5 to 7 days by qualitative plate cultures, culture-based assays (BacT/ALERT 3D), and rapid (PLT PGD) tests. RESULTS: C. perfringens grew in only 3 of 8 apheresis PLT units after inoculation at either high (2 units) or low (1 unit) concentrations. The PGD test detected the isolate after 5 days in 1 unit with 4.7 × 10(5) CFUs/mL but failed at five other time points in units with greater than 10(5) CFUs/mL. CONCLUSION: C. perfringens demonstrated variable growth in spiked PLTs and was not consistently detected by a rapid test even when high levels of contamination were present. The case underscores the importance of direct observation during transfusion, appropriate clinical management, and immediate reporting of suspected septic reactions to the blood center.

The residual risk of transfusion-related acute lung injury at the American Red Cross (2008-2011): limitations of a predominantly male-donor plasma mitigation strategy.

BACKGROUND: The American Red Cross began preferentially distributing plasma from male donors in 2007 and subsequently observed an 80% decrease in reported cases of transfusion-related acute lung injury (TRALI) after plasma transfusion. Plasma distributions from male donors now exceed 99% for groups A, B, and O, but only approximately 60% for group AB. We evaluated the ongoing risk of TRALI and the ABO blood group of involved plasma donors. STUDY DESIGN AND METHODS: The rate of suspected TRALI per distributed components before (2006) and after (2008-2011) implementing the predominantly male-donor plasma strategy is compared. RESULTS: The risk of TRALI from the general inventory of distributed plasma decreased significantly from 18.6 cases per million units in 2006 to 4.2 cases per million units in 2008 to 2011 (p < 0.0001). However, the risk from AB plasma did not change (26.3 cases per million units) and was significantly greater than group A, B, and O plasma in 2008 to 2011 (1.8 per million units; odds ratio 14.5; 95% confidence interval, 6.8-30.9). Group AB plasma from female donors with HLA or HNA antibodies accounted for 14 of 28 (50%) of TRALI cases but less than 4% of all plasma units distributed in 2008 to 2011. CONCLUSION: The risk of TRALI after plasma transfusion has been markedly reduced for blood groups A, B, and O but not for AB, reflecting continued reliance on group AB plasma from female donors to meet increasing demand.

Improved safety for young whole blood donors with new selection criteria for total estimated blood volume.

BACKGROUND: Young age, first-time donation status, and estimated blood volume (EBV) are leading determinants of syncopal complications after whole blood donation. We evaluated a multifaceted safety initiative and more restrictive selection criteria for whole blood donation by individuals younger than 19 years. STUDY DESIGN AND METHODS: Measures introduced over 2 years addressed donor education, drive environment and supervision, and new eligibility criteria for EBV of 3.5 L or more based on height, weight, and sex for individuals younger than 19 years. Presyncopal and syncopal reactions after whole blood donation during the school year in the baseline, transitional (2008), and full implementation (2009) periods were evaluated. RESULTS: Young donors (16- to 18-years-olds) gave 754,402 and 710,922 whole blood donations in the 2008 and 2009 school years accounting for 16% of the total collections in both 9-month study periods. The new selection criteria were associated with a significant reduction in the reaction rates among 16- to 18-year-olds. Sixteen-year-old donors had the greatest decrease in 2009 compared to baseline for presyncopal reactions (10.5% vs. 7.3%; odds ratio [OR], 0.67; 95% confidence interval [CI], 0.65-0.69) and syncope (43.1 vs. 37.1 per 10,000 donations; OR, 0.86; 95% CI, 0.77-0.96). Donor subgroup analysis by sex, age, and donation status demonstrated that age-related differences in reaction rates were eliminated in 2009. CONCLUSION: The safety initiative with new selection criteria for EBV led to decreased complications among donors 16 to 18 years old, such that the risk for 16-year-olds was no longer different from that observed for 19-year-olds in the analysis stratified by age, sex, and donation status.

The relative safety of automated two-unit red blood cell procedures and manual whole-blood collection in young donors.

BACKGROUND: Automated red blood cell (RBC) apheresis offers the advantage of collecting 2 units of RBCs (2RBC) from one donation, but may expose donors to procedure-related risks. This study evaluated the relative safety of 2RBC compared to whole-blood (WB) donation with a focus on young donors. STUDY DESIGN AND METHODS: Adverse reactions recorded at the collection site or requiring outside medical care were compared after 4,348,686 WB and 206,570 2RBC donations in 26 regional blood centers. RESULTS: 2RBC donors were more likely than WB donors to be male (91.6% vs. 50.3%) and repeat donors (84.0% vs. 81.0%). The overall complication rate was higher for 2RBC than WB collections (627.9 vs. 435.1 per 10,000; odds ratio [OR], 1.44; 95% confidence interval [CI], 1.41-1.47), but more than 96% of all reactions were minor in severity. For donors younger than 20 years, adverse events were equally or less common after 2RBC than after WB donation, but were more common after 2RBC for donors 20 years or older. The rate of major systemic complications was significantly lower for 2RBC than WB donations in all age groups (10.2 vs. 14.3 per 10,000 collections; OR, 0.71; 95% CI, 0.62-0.82). Overall, the need for outside medical care was similar for 2RBC and WB collections (3.4 vs. 4.2 per 10,000 donations, respectively), but significantly less likely after 2RBC donation for donors less than 20 years old (3.8 vs. 7.0. per 10,000 donations; OR, 0.53; 95% CI, 0.32-0.89). CONCLUSION: 2RBC collection procedures, as currently performed in the American Red Cross, are associated with fewer immediate adverse reactions in young donors and have a comparable safety profile in older donors. These data support the collection of 2RBC from young donors.

Limiting and detecting bacterial contamination of apheresis platelets: inlet-line diversion and increased culture volume improve component safety.

BACKGROUND: Septic transfusion reactions to apheresis platelets (PLTs) continue to occur despite preventive measures. This study evaluated the effect of two operational changes designed to reduce bacterial risk: 1) introducing inlet-line sample diversion on two-arm procedures and 2) increasing the sample volume cultured from 4 to 8 mL from all donations. STUDY DESIGN AND METHODS: Aerobic culture results and septic transfusion reactions reported between December 1, 2006, and July 31, 2008 (Period 2), were compared to March 1, 2004, to May 31, 2006 (Period 1). RESULTS: During Period 2, a total of 781,936 apheresis PLT collections were cultured, of which 130 donations (1:6015) were confirmed positive and 9 (1:86,882) had negative culture results but were associated with 11 septic reactions. Confirmed-positive cultures from two-arm procedures decreased (27.2 to 14.7 per 105 collections; odds ratio [OR], 0.54; 95% confidence interval [CI], 0.41-0.70) in Period 2, owing to a lower rate of skin flora contamination. Detection of contamination of one-arm collections significantly increased by 54% in Period 2 (13.7 vs. 21.1 per 105 collections; OR, 1.54; 95% CI, 1.05-2.27). Fewer septic transfusion reactions occurred in Period 2, but the difference did not reach significance (1.7 vs. 1.2 per 105 donations; OR, 0.68; 95% CI, 0.30-1.53). CONCLUSION: Inlet-line diversion decreased bacterial contamination during two-arm collections by more than 46%. Concurrently, doubling the sample volume was associated with a 54% relative increase in culture sensitivity. These interventions act cooperatively to decrease bacterial risk.

Bacterial contamination of whole-blood-derived platelets: the introduction of sample diversion and prestorage pooling with culture testing in the American Red Cross.

BACKGROUND: Bacterial sepsis following whole blood-derived platelet (WBP) transfusion has remained a substantial patient risk, primarily due to a lack of practical and effective means to limit or detect bacterial contamination. We describe the risk of reported septic reactions to WBPs and the introduction of prestorage-pooled whole blood-derived platelets (PSPs) collected using initial sample diversion and cultured for bacterial contamination. STUDY DESIGN AND METHODS: Product qualification and quality control (QC) testing with the Acrodose PL system (Pall Medical) were evaluated in four regional blood centers. Bacterial contamination risk was assessed by review of reported septic transfusion reactions to WBPs and by aerobic QC culture of leukoreduced PSPs utilizing automated microbial detection system cultures (BacT/ALERT 3D, bioMérieux). RESULTS: Before implementing PSPs (January 2003-December 2006), we distributed 2,535,043 WBP units and received 20 reports of septic reactions including 2 fatalities (7.9 per million [1:126,752] reactions and 0.79 per million [1:1,267,522] fatalities). In October 2006, PSPs were effectively implemented with a product qualification success rate of 99.6 percent and a mean yield of 4.0 x 10(11) platelets (PLTs) per pool. Whole blood collection sets with sample diversion technology were introduced during the operational trial and decreased the rate of confirmed-positive bacterial culture of PSPs from 2111 (1:474) to 965 (1:1036) per million (odds ratio, 0.46; 95% confidence interval, 0.22-0.95). No septic reactions to PSPs were reported (25,936 PSP units distributed). CONCLUSION: Sample diversion and bacterial culture are effective methods to reduce bacterial risk with WBP transfusion. Bacterial contamination of PSPs was assessed at 5.8-fold our current rate for apheresis PLTs utilizing comparable culture protocols.

The American Red Cross donor hemovigilance program: complications of blood donation reported in 2006.

BACKGROUND: The American Red Cross (ARC) initiated a comprehensive donor hemovigilance program in 2003. We provide an overview of reported complications after whole blood (WB), apheresis platelet (PLT), or automated red cell (R2) donation and analyze factors contributing to the variability in reported complication rates in our national program. STUDY DESIGN AND METHODS: Complications recorded at the collection site or reported after allogeneic WB, apheresis PLT, and R2 donation procedures in 36 regional blood centers in 2006 were analyzed by univariate and multivariate logistic regression. RESULTS: Complications after 6,014,472 WB, 449,594 PLT, and 228,183 R2 procedures totaled 209,815, 25,966, and 12,282 (348.9, 577.5, and 538.3 per 10,000 donations), respectively, the vast majority of which were minor presyncopal reactions and small hematomas. Regional center, donor age, sex, and donation status were independently associated with complication rates after WB, PLT, and R2 donation. Seasonal variability in complications rates after WB and R2 donation correlated with the proportion of donors under 20 years old. Excluding large hematomas, the overall rate of major complications was 7.4, 5.2, and 3.3 per 10,000 collections for WB, PLT, and R2 procedures, respectively. Outside medical care was recorded at similar rates for both WB and automated collections (3.2 vs. 2.9 per 10,000 donations, respectively). CONCLUSION: The ARC data describe the current risks of blood donation in a model multicenter hemovigilance system using standardized definitions and reporting protocols. Reported reaction rates varied by regional center independently of donor demographics, limiting direct comparison of different regional blood centers.

Adverse reactions to allogeneic whole blood donation by 16- and 17-year-olds.

CONTEXT: Donations by minors (16- and 17-year-olds) now account for approximately 8% of the whole blood collected by the American Red Cross, but young age and first-time donation status are known to be independent risk factors for donation-related complications. OBJECTIVE: To evaluate adverse reactions to allogeneic whole blood donation by 16- and 17-year-olds compared with older donors in American Red Cross blood centers. DESIGN, SETTING, AND PARTICIPANTS: Prospective documentation of adverse events among 16- and 17-year-old donors using standardized collection protocols, definitions, and reporting methods in 2006. Data were from 9 American Red Cross blood centers that routinely collect from 16- and 17-year-olds, a population that provides 80% of its donations at high school blood drives. MAIN OUTCOME MEASURES: Rate of systemic (syncopal-type) and phlebotomy-related donor complications per 10,000 collections. RESULTS: In 2006, 9 American Red Cross regions collected 145,678 whole blood donations from 16- and 17-year-olds, 113,307 from 18- and 19-year-olds, and 1,517,460 from donors aged 20 years or older. Complications were recorded in 15,632 (10.7%), 9359 (8.3%), and 42,987 (2.8%) donations in each corresponding age group. In a multivariate logistic regression model, young age had the strongest association with complications (odds ratio [OR], 3.05; 95% confidence interval [CI], 2.52-3.69; P < .001), followed by first-time donation status (OR, 2.63; 95% CI, 2.24-3.09; P < .001) and female sex (OR, 1.87; 95% CI, 1.62-2.16; P < .001). Infrequent but medically relevant complications, in particular physical injury from syncope-related falls, were significantly more likely in 16- and 17-year-old donors (86 events; 5.9/10,000 collections) compared with 18- and 19-year-old donors (27 events; 2.4/10,000 collections; OR, 2.48; 95% CI, 1.61-3.82) or adults aged 20 years or older (62 events; 0.4/10,000 collections; OR, 14.46; 95% CI, 10.43 -20.04). Sixteen-year-old donors who experienced even a minor complication were less likely to return to donate within 12 months than 16-year-olds who experienced uncomplicated donations (52% vs 73% return rate; OR, 0.40; 95% CI, 0.36-0.44). CONCLUSIONS: A higher incidence of donation-related complications and injury occurs among 16- and 17-year-old blood donors compared with older donors. The increasing dependence on recruiting and retaining young blood donors requires a committed approach to donor safety, especially at high school blood drives.

Bacterial screening of apheresis platelets and the residual risk of septic transfusion reactions: the American Red Cross experience (2004-2006).

BACKGROUND: The American Red Cross initiated systemwide bacterial testing of all apheresis platelet (PLT) collections in March 2004, yet continues to receive reports of septic reactions after transfusion of screened components. STUDY DESIGN AND METHODS: The rates of confirmed bacterial contamination of apheresis PLT collections detected by prospective quality control (QC) testing, and by surveillance of reported septic reactions to screened-negative apheresis PLTs, were analyzed according to the technology utilized for collection. RESULTS: Between March 1, 2004, and May 31, 2006, bacterial culture testing was performed on 1,004,206 donations; of these, 186 (1:5,399) had confirmed-positive culture results. Transfusion of all but 1 of the associated 293 components was prevented. A significantly higher rate of confirmed-positive bacterial cultures was seen with products collected utilizing two-arm collection procedures compared to one-arm procedures (22.7 vs. 11.9 per 10(5) donations; odds ratio [OR], 1.9; 95% confidence interval [CI], 1.4-2.7). During this period, 20 septic transfusion reactions were reported, including 3 fatalities (1:498,711 fatalities per distributed component), which implicated screened-negative apheresis PLT products. The frequency of septic reactions was 4.7-fold higher for collections utilizing two-arm procedures (1:41,173; 95% CI, 1:25,000-1:66,667) compared to collections from one-arm procedures (1:193,305; 95% CI, 1:52,632-1:500,000; OR, 4.7; 95% CI, 1.2-18.4); most septic reactions (16 of 20) were due to Staphylococcus spp. and occurred on Day 5 (13 of 20) after collection. CONCLUSION: PLT contamination with bacteria that evade detection by QC culture remains a significant residual transfusion risk, in particular for older PLTs and skin-commensal bacteria in components collected by two-arm apheresis procedures during the study period.