Detection of bacterial contamination in apheresis platelets: is apheresis technology a factor?

BACKGROUND: Apheresis platelet (AP) contamination may be influenced by manufacturing methods because bacteria are subject to the same forces that permit separation of blood cells. This study assesses whether apheresis technology influences in-process detection of bacterial contamination. STUDY DESIGN AND METHODS: Blood Systems, Inc. (BSI) and New York Blood Center (NYBC) use Amicus and Trima devices to collect APs. Manufacturing (arm disinfection and in-line diversion) was consistent for both devices in the study period. Detection was performed using BacT/ALERT. True-positive (TP) rates were calculated and significance testing was performed using chi-square tests separately for BSI and NYBC. For BSI, multivariable logistic regression analysis was also performed to identify factors associated with TP results. RESULTS: For BSI, there were 49 TPs in 354,946 donations (1.4/10,000): 2.5 per 10,000 for Amicus and 1.0 per 10,000 for Trima (p < 0.05). Multivariable logistic regression analysis showed significant association between TP and devices (odds ratio, 2.8; 95% confidence interval [CI], 1.01-8.0) and for one collection region. For NYBC, there were 18 TPs in 161,840 donations (1.1/10,000): 2.1 per 10,000 for Amicus and 0.4 per 10,000 for Trima (p < 0.05). CONCLUSIONS: The TP rate was significantly higher in Amicus collections than in Trima collections at NYBC and BSI. These results do not allow for conclusions regarding the relative clinical risk of PLTs collected by Amicus and Trima. Future evaluations of component quality and clinical outcomes should consider different collection technologies.

Predictors of hemoglobin recovery or deferral in blood donors with an initial successful donation.

BACKGROUND: Donation eligibility is based on hemoglobin (Hb) level among other factors. This study assesses factors that influence Hb levels among first-time (FT) donors returning for a second donation. STUDY DESIGN AND METHODS: Allogeneic FT donors who successfully donated a red blood cell (RBC)-containing donation on their index presentation and returned to donate at least once more between August 1, 2009, and July 31, 2012, were included. Interdonation intervals and delta Hb (subsequent donation - index donation value) were calculated. Multivariable logistic regression and survival analysis methods were used to determine factors associated with 1) Hb recovery to preindex donation value or 2) deferral at the second presentation. RESULTS: During the study, 135,040 FT donors returned to donate. Overall, 44% of donors returned with a Hb level at or above their index value (defined as recovery for this study), 48.1% for males and 39.9% for females. Logistic regression revealed that the factor most strongly associated with Hb recovery was index Hb, with lower Hb having much higher odds of recovery. Shorter interdonation intervals were associated with decreased likelihood of recovery. Certain demographic characteristics were also associated with higher odds of recovery. Factors associated with deferral were similar to the factors associated with recovery, except for donor sex. CONCLUSIONS: As early as the second blood donation, allogeneic donors can be differentiated into two subpopulations: those who recover to index Hb levels and those who do not. Current data routinely collected by US blood centers cannot reliably distinguish between the two groups.

Predicting improvement in detection of bacteria in apheresis platelets by maintaining constant component sampling proportion.

BACKGROUND: In spite of interventions, approximately 1000 per 1,000,000 platelet (PLT) collections are contaminated with bacteria at collection. The current prestorage culture procedure at some blood centers is to inoculate a fixed volume from the collection bag (4-8 mL) regardless of collection volume. The sensitivity of early testing varies with the percent of collection volume sampled. We applied the Poisson model to determine whether sampling larger volumes might increase detection at pertinent contamination levels. STUDY DESIGN AND METHODS: The intervention was testing a fixed proportion of the collection volume from single, double, and triple collections. The Poisson model was applied to blood center data to calculate weighted average detection. Model 1 consisted of inoculating 3.2% of the collection volume from single, 1.6% from double, and 1.2% from triple PLT procedures (8 mL in each case). Model 2 consisted of inoculating 3.8% of the collection volume from all PLT procedures. Volume-related and non-volume-related contamination mechanisms were evaluated. RESULTS: Testing constant proportions of the collection volume (Model 2) increases percent detection over testing constant volumes (Model 1) (68% vs. 41% detection if contamination is 30 colony-forming units (CFUs)/collection bag and 17% vs. 9% detection if contamination is 5 CFUs/collection bag). At low levels of contamination (approx. 5 CFUs/bag), the intervention might double the number of contaminated units detected. CONCLUSION: Based on the application of the Poisson model to detection of bacteria in PLT concentrates, inoculating cultures with slightly consistent proportions of the collection volume should lead to a reduction in false negative tests and in the number of contaminated units transfused.

Improving the performance of culture-based bacterial screening by increasing the sample volume from 4 mL to 8 mL in aerobic culture bottles.

BACKGROUND: In the setting of bacterial detection of apheresis platelets (PLTs), the manufacturer recommended PLT inoculation volume for BacT/ALERT culture bottles (bioMérieux) ranges from 4 to 10 mL. This study compares the rate of capture of true-positive (TP) contaminations between aerobic culture bottles inoculated with either 4 or 8 mL of sample and assesses if a larger sample volume reduces time to detection. STUDY DESIGN AND METHODS: Detection of TP samples and mean time to detection were compared for 4- and 8-mL samples collected between September 1, 2003, and May 2, 2011. RESULTS: A total of 180,263 and 283,114 PLT collections were tested with an 8- and 4-mL sample, respectively. Analysis of TP rates by volume sampled show an increase in the rate of detection of TP with the 8-mL sample relative to the 4-mL sample (139 vs. 106 per million events; odds ratio, 1.31; 95% confidence interval, 0.77-2.23). Comparison of mean time to detection for TP shows a decrease in mean time to detection using 8 mL compared with 4 mL (12.36 ± 3.7 hr to 15.97 ± 6.3 hr, p = 0.012). CONCLUSION: Doubling the sample volume to 8 mL showed a trend in improvement for the rate of detection of TP and shortened the mean time of detection for TP by 23% when compared to a sample volume of 4 mL. The decrease in mean time to detection using a larger sample volume suggests that a shorter release time after inoculation could be achieved without significantly increasing patient risk.

Epidemiologic and laboratory findings from 3 years of testing United States blood donors for Trypanosoma cruzi.

BACKGROUND: At most blood centers in the United States routine testing of donations for Trypanosoma cruzi using an enzyme-linked immunosorbent assay (ELISA) is followed by supplemental testing by radioimmunoprecipitation assay (RIPA). The objective of this study was to report the results of routine testing and risk factor data from allogeneic blood donors. STUDY DESIGN AND METHODS: T. cruzi testing data from January 2007 through December 2009 were analyzed, and risk factor interviews and follow-up studies were conducted on seroreactive donors. Prevalences of confirmed infection and risk factors associated with infection were assessed using logistic and multivariable logistic regression. RESULTS: Of 2,940,491 allogeneic donations from 1,183,076 donors, 305 (0.01% per donation tested and 0.026% per blood donor) were repeat reactive (RR) and 89 of those were confirmed positive by RIPA, yielding an overall seroprevalence of 1 per 33,039 donations and 1 per 13,292 donors. Country of birth and US blood center location differences in the seroprevalence of T. cruzi were evident. The odds of confirmed infection were highest if the donor reported having been bitten by the reduviid (kissing) bug (odds ratio [OR], 76.1; 95% confidence interval [CI], 11.1-3173) followed by having lived in a rural area of Latin America (OR, 38.6; 95% CI, 15.1-102.5). In multivariable analyses, having spent 3 months or more in Mexico or Central and/or South America was associated with the highest odds of RIPA-confirmed infection (OR, 8.5; 95% CI, 2.7-26.5). Polymerase chain reaction (PCR) testing of ELISA RR donors exhibited low sensitivity (1/22 [4%] RIPA-confirmed donors was PCR positive). CONCLUSION: Risk factors for confirmed infection in US blood donors are consistent with the known epidemiology of Chagas disease. Blood donors or transfusions do not substantially contribute to the burden of T. cruzi infection in the United States.

Interventions to reduce the vasovagal reaction rate in young whole blood donors.

BACKGROUND: There have been multiple reports concerning the predictors of fainting reactions in blood donors, but few attempts to reduce the rates of fainting reactions with concomitant rigorous attempts to monitor the success of the interventions. STUDY DESIGN AND METHODS: We used a retrospective observational cohort study design, comparing the likelihood of reaction from 213,031 allogeneic whole blood donations made by 17- to 22-year-old donors in two separate 12-month periods before and after the implementation of interventions to reduce reactions. The interventions were 1) a limit on the maximum percentage of estimated blood volume young donors could donate, 2) encouraging applied muscle tension during donation, and 3) providing approximately 500 mL of water before donation. Reactions were defined by severity and time in relation to the end of phlebotomy and documented according to standard procedures. Data analysis included comparison of stratified reaction rates and multivariable logistic regression analysis. RESULTS: The interventions decreased the aggregate reaction rates in male and female donors by 24% (p < 0.0001). There was a 25% decrease in delayed reactions (p = 0.0006) and a 38% decrease in off-site reactions (p = 0.001) in female donors. The impact of the three interventions together on reaction rate was greater than the combined impact of exercises and water provision. Multivariable modeling showed that the interventions reduced reactions but did not prevent their occurrence in identified higher risk groups. CONCLUSION: The interventions to reduce vasovagal reactions in whole blood donors were effective. Future efforts to reduce reactions in blood donors can build on the strengths and avoid the weaknesses identified while conducting and analyzing the data from this study.

Physiologic strategies to prevent fainting responses during or after whole blood donation.

Vasovagal syncope (VVS) is a consistent, but infrequent (0.1%-0.3%) complication of volunteer, whole blood donation. Given the large number of blood donations, a significant number of donors is involved. Syncope occasionally leads to injury. Recent rigorous data collection and analysis have led to the association of a small number of donor and donation factors with the risk of syncope. An analysis of the time course of syncope reactions among approximately 500,000 whole blood donors suggests that there are three distinct periods of risk for vasovagal reactions before, during, and after phlebotomy. This review examines the physiologic mechanisms that contribute to these periods of increased risk including the direct effects of removal of approximately 500 mL of whole blood, the psychological stress of instrumentation and giving blood (i.e., fear of needles, pain, and the sight of blood), and the orthostatic effects superimposed on a hypovolemic state after the donation. Specifically, we describe interventions that have been useful in controlling VVS in patients with fainting syndromes and we examine the potential of these interventions in the blood donation context, based on the physiologic principles involved. Finally, we propose an intervention (dietary replacement of salt lost with blood donation) that has not been applied in transfusion medicine previously but which has the potential to reduce risk.

Delayed adverse reactions to blood donation.

BACKGROUND: Blood donation is safe, but a small proportion of donors have delayed and/or off-site reactions that have the potential to lead to serious injury. This retrospective study sought to identify risk factors for delayed reactions (DRs). STUDY DESIGN AND METHODS: The records of 793,293 allogeneic whole blood and apheresis donations in 2007 were assessed for vasovagal reactions. Donor demographic, biometric, and clinical measurements were captured. Incidents related to needle insertion and mild reactions were excluded. Based on the reaction onset time relative to the procedure end time, reactions were classified as delayed (>15 min) or immediate (

The impact of discontinuation of 7-day storage of apheresis platelets (PASSPORT) on recipient safety: an illustration of the need for proper risk assessments.

BACKGROUND: Seven-day stored apheresis platelets (APs) were withdrawn from the US market after detection of two culture-positive units from 2571 tested at outdate in the PASSPORT surveillance study. The impact of this discontinuation on recipient safety was explored using mathematical modeling. STUDY DESIGN AND METHODS: Risk models for septic transfusion reactions (STRs) and transfusion-related acute lung injury (TRALI) were developed. Key assumptions were 400,000 annual APs transfused, equivalent STR risk for platelets (PLTs) stored for 5 days or more and zero for PLTs stored for less than 5 days, whole blood-derived PLTs (WBplts) administered in 5-unit pools, a 4.6-fold higher risk of false-negatives with surrogate versus culture-based bacterial testing, an AP TRALI risk between 1 per 1000 and 1 per 10,000, and a delay in TRALI risk reduction implementation in some centers by 6 to 12 months due to limited PLT availability. RESULTS: STR risk could increase, decrease, or remain the same depending on the percentage of inventory replaced by surrogate-tested WBplts versus culture-tested apheresis or whole blood PLTs. A delay in TRALI risk reduction implementation is likely to result in a comparable or greater risk during the delayed implementation period than the safety achieved with regard to STRs, even in the most favorable case scenario. CONCLUSION: A comprehensive risk assessment should have been conducted before the decision to discontinue PASSPORT. Risk assessments using accepted methods (and actual data when available) should precede any major blood safety decisions.

West Nile virus testing experience in 2007: evaluation of different criteria for triggering individual-donation nucleic acid testing.

BACKGROUND: In 2007, clients served by Blood Systems Laboratories used variable approaches for triggering West Nile virus (WNV) RNA individual-donation (ID) nucleic acid testing (NAT). These included two minipool (MP) NAT-reactive donations and a greater than 1:1000 rate in a 7-day interval (primary trigger), criteria based on one MP-NAT-reactive donation when there was WNV activity in overlapping and/or adjacent geographic areas (neighbor trigger), or zero MP-NAT-reactive donation (self-trigger). STUDY DESIGN AND METHODS: The Procleix WNV assay was used in either a 16-sample MP or an ID format. NAT-repeat reactivity or anti-immunoglobulin M (IgM) positivity defined true positives (TPs). TPs that were negative on 1:16 dilution testing were considered ID-NAT yield cases. RESULTS: WNV NAT performed on 1,217,929 donations identified 162 TPs; 87 were detected by MP (rate of 0.008%) and 75 by ID (rate of 0.10%; p < 0.0001). There were 34 ID-NAT yield cases, including 4 IgM/immunoglobulin G (IgG)-negative and 9 IgM-positive/IgG-negative donations. Rates of yield cases by primary, neighbor, and self-triggering were 0.077, 0.052, and 0.004% (p = 0.0003). None of 11 ID-NAT yield cases detected by the neighbor trigger would have been detected if the primary trigger had been used. CONCLUSIONS: Primary triggering criteria identified 21 viremic donations that would have been missed by MP testing; however, 11 other low-level viremic donations required more stringent criteria (e.g., neighbor trigger) for detection. It is reasonable to adopt more stringent ID-NAT triggers, including elimination of the rate criterion and triggering on one NAT-reactive donation for regions adjacent to centers which have already triggered.

Screening the blood supply for West Nile virus RNA by nucleic acid amplification testing.

BACKGROUND: The use of nucleic acid amplification tests of "minipools" of 16 samples to screen blood donors for West Nile virus RNA began in July 2003. We report the yield and characteristics of positive donations and the incremental yield and safety of nucleic acid amplification tests of individual donations. METHODS: Reactive minipools were analyzed to identify the individual reactive donations. For the regions with the highest yield on minipool testing, retrospective nucleic acid amplification testing was performed on individual donations that were negative on minipool testing. Reactive donations were confirmed by alternative nucleic acid amplification tests and IgM and IgG tests, and donors were followed to document seroconversion. RESULTS: From July 1 through October 31, 2003, 677,603 donations were prospectively screened for West Nile virus by minipool testing, yielding 183 confirmed viremic donations (0.027 percent, or 1 in 3703 donations). Retrospective individual testing of 23,088 donations from high-prevalence regions that were negative on minipool testing yielded 30 additional units with a low level of viremia, with 14 additional viremic units detected by prospective testing of individual donations late in the 2003 transmission season. Of all the viremic units detected, 5 percent were detected only by individual testing and were negative for IgM antibody, 29 percent were detected by individual testing after IgM seroconversion, and 66 percent were detected by minipool testing. West Nile virus infection was confirmed in both recipients of IgM-negative units that were reactive on individual testing, whereas neither recipient of antibody-positive blood components that were reactive on individual testing was infected. In 2004, prospective testing of individual donations in regions that yielded donations that were reactive on minipool testing resulted in a 32 percent incremental yield of units with a low level of viremia that would have been missed by minipool testing. CONCLUSIONS: Although nucleic acid amplification testing of minipools of blood donations prevented hundreds of cases of West Nile virus infection in 2003, it failed to detect units with a low level of viremia, some of which were antibody-negative and infectious. These data support the use of targeted nucleic acid amplification testing of individual donations in high-prevalence regions, a strategy that was implemented successfully in 2004.

Faint and prefaint reactions in whole-blood donors: an analysis of predonation measurements and their predictive value.

BACKGROUND: A small proportion of blood donors have adverse reactions. The purpose of this study was to determine predictors of faint and significant hypotensive reactions that could serve as targets for interventions to reduce reactions, thus improving the blood donation experience for those at higher risk of reactions and reducing the risk of serious adverse events. STUDY DESIGN AND METHODS: The records of 422,231 allogeneic whole-blood donations from a 9-month period were assessed for adverse reactions. Incidents related to needle insertion, such as hematoma, were excluded. Demographic, biometric, and clinical measurements were collected. Reactions were analyzed by multivariate logistic regression analysis comparing donors with any adverse reaction to donors without reactions and by stratified rates according to reaction severity. RESULTS: The overall reaction prevalence was 1.43 percent. Of the reactions, 63, 29, and 8 percent were classified as mild, moderate, and severe, respectively. Markers of reactions were age, sex, race, blood volume, blood pressure, pulse, and body mass index. Compared to donors without reactions, the strongest predictor of a reaction was a donor's blood volume of less than 3500 mL (odds ratio [OR], 2.9; 95% confidence interval [CI], 2.57-3.23). Age and first-time status were also associated with a significantly higher risk of reaction with 17- to 18-year-olds (OR, 2.8; 95% CI, 2.59-2.98) and 19- to 24-year-olds (OR, 2.39; 95% CI, 2.23-2.56) at higher risk compared to 25- to 65-year-olds and first-time donors at higher risk compared to repeat donors (OR, 2.2; 95% CI, 2.07-2.33). CONCLUSION: The results of this study are helpful in identifying donors at risk for adverse reactions and in understanding the contributors to reactions. Donor blood volume was an unexpectedly strong predictor of reaction. Potential interventions to reduce the frequency of reaction are discussed.

Bacterial detection in apheresis platelets: blood systems experience with a two-bottle and one-bottle culture system.

BACKGROUND: United Blood Services (UBS) began bacterial testing of platelets (PLTs) using one-bottle cultures in September 2003. Collection of 7-day PLTs using two-bottle cultures began in April 2006. This study compares our experience using both systems. STUDY DESIGN AND METHODS: PLTs from 13 UBS regional centers cultured from September 1, 2003, to September 1, 2007, were included in the analysis. Positive-signal bottles from a commercially available microbial detection system (BacT/ALERT, bioMérieux) were sent, with corresponding PLTs if available, for confirmatory testing using plate culture media. AABB definitions were used with modifications. RESULTS: A total of 51,265 7-day PLT collections and 191,521 5-day PLT collections were tested with bacterial cultures. The overall true-positive (TP) rate for the two-bottle system (1:8544) was comparable to the TP rate with the previous one-bottle system (1:6344). In three of six yield cases, only the anaerobic bottle was positive (two cases of Group D Streptococci, one case of Corynebacterium spp.). The false-positive (FP) and indeterminate (IND) rates in the anaerobic bottle (1:1767 and 1:1830, respectively) were significantly higher than those in the aerobic bottle (1:6408 and 1:17,088, respectively; p < 0.001). One confirmed transfusion-related septic reaction, classified as a late TP after investigation, was reported out of 242,786 tested PLT donations. CONCLUSION: The rate of TP cases by the two-bottle system was not increased over the one-bottle system, although anaerobic-bottle-only positive cases were detected. FP and IND rates were increased in the two-bottle system, attributable to the anaerobic bottle. Observation of only one documented transfusion-related septic reaction in 4 years of bacterial screening at UBS is reassuring, although limitations in passive surveillance and higher rates of reactions reported by others indicate the need for continued vigilance.