Quality Improvement After Multiple Fatal Transfusion-Transmitted Bacterial Infections

Quality Improvement After Multiple Fatal Transfusion-Transmitted Bacterial Infections Abstract Objectives Transfusion-transmitted bacterial infection (TTBI) from platelet components is likely underrecognized and can be fatal. Twenty-four-hour prospective culture was felt to be insufficiently preventive after multiple TTBIs occurred and strategies to improve safety were sought. Methods Two fatal and one severe TTBIs occurred from a split-apheresis platelet donation contaminated with Klebsiella pneumoniae. Improvement opportunities were identified and corrective and preventive action (CAPA) followed. Results To mitigate bacterial contamination and improve detection sensitivity, additional prospective culture 48 hours postcollection was implemented. Since implementation, secondary cultures have caught two true positives (0.01%) missed by 24-hour culture. Bacterial testing at issue and pathogen reduction were later implemented as an added layer of safety. Conclusion While rare, TTBI is a prominent cause of morbidity and mortality from contaminated platelets. The approach to CAPA presented here may lower the risk of future transfusion-transmitted infections but must be weighed against potential added costs. Transfusion-transmitted bacterial infection, Quality improvement, Corrective and preventive action, Testing at issue, Pathogen reduction It is well documented that platelet components are the most common source of septic transfusion reactions given their room temperature storage conditions. Rates of contamination have been estimated from 1 in 1,000 to 10,000 units, usually from donor skin flora or occult bloodstream infection.1-3 Transfusion-transmitted bacterial infections (TTBIs) are likely underrecognized clinically, but fatalities continue to be reported to the US Food and Drug Administration (FDA) each year.4 In the United States, between 2011 and 2015, microbial-contaminated transfusion fatalities were the fourth most common cause of death, accounting for 10% of the total transfusion-related fatalities.5 Most fatal bacterially contaminated platelet units were due to Gram-negative bacteria, and one reported fatality from 2011 to 2015 was due to Klebsiella pneumoniae.5 While stringent requirements for bacterial detection of platelet products have been in place for many years, they are insufficient to prevent all potential TTBIs. Because apheresis platelet collections can yield multiple co-components, hemovigilance with timely reporting of suspected transfusion reactions can be critical for expeditious quarantining of any co-components remaining in inventory. To maximally prevent adverse outcomes from TTBI, a more comprehensive strategy may be undertaken. An approach to improve the sensitivity of bacterial detection is discussed here along with eventual implementation of testing at issue and pathogen reduction technology. Materials and Methods Three cases of TTBI from a single apheresis platelet donation contaminated with K pneumoniae occurred. TTBIs are considered serious adverse events that can be fatal (as demonstrated here). The clinical and laboratory characteristics were reviewed in detail. After identification and diagnosis, hemovigilance was examined to identify opportunities for improvement. The current hemovigilance process at our institution was examined first, and root cause analyses were performed subsequently. In addition to the current process, corrective action to further minimize TTBI risk and possible preventive action surrounding other potential infectious agents (viruses, parasites) was sought. First, an additional prospective culture protocol at 48 hours was implemented to identify bacterial contamination. Because platelet components are stored at room temperature, it was hypothesized that low-level contamination missed by the current prospective culture protocol would be caught by the additional 48-hour prospective culture along with greater sampling volumes as an approach to enhance detection sensitivity. The rationale for greater sampling volume was supported by previous studies showing increased sensitivity.6,7 Surveillance of secondary cultures was performed and utility evaluated. As a result of the TTBI events, the reporting donor center quickly implemented a double-culture protocol with the BacT/ALERT system (bioMérieux, Marcy-l’Étoile, France) in an attempt to increase sensitivity. Over approximately 5 years, a 10-mL aliquot was taken from each platelet donation at 24 hours postcollection for aerobic and anaerobic cultures, respectively, and another 10-mL aliquot for aerobic culture was obtained at time 48 hours. If no growth was detected in either culture at 56 hours after the donation, the product was released for transfusion. These bottles were incubated for the entire life of the product. Previously, 4-mL aliquots were used for an aerobic and anaerobic culture at time 24 hours and the product released at time 48 hours if cultures were negative. The secondary culture was a corrective action to mitigate the risk of a previously identified problem. Preventive action was subsequently pursued and the decision was made to implement pathogen reduction technology (Intercept; Cerus Corporation, Concord, CA) to mitigate the potential risk of problems that have not yet occurred (ie, transfusion-transmitted infections due to other infectious agents such as viruses and parasites). Transfusion reactions were reviewed after implementation of these processes. Results TTBI Cases: Brief Description The first patient received two apheresis platelet aliquots from the offending donation during surgery. K pneumoniae was identified by blood culture and peripheral smear. The patient developed lactic acidosis and disseminated intravascular coagulation (DIC) and ultimately died. The second patient received an apheresis platelet aliquot from the contaminated donation as an outpatient. During the infusion, the patient experienced vomiting and hypoxia, and acute lung injury was later identified. While blood cultures were negative, the patient was taking antimicrobials to which the offending bacterium was later found to be susceptible. After prolonged hospitalization, the patient survived. The third patient received an apheresis platelet aliquot of the contaminated product. The patient became frankly septic, and K pneumoniae was again identified. The patient developed multiorgan failure and died a few days later. K pneumoniae was also isolated from the RBC unit used to prime the extracorporeal life support (ECLS) machine likely due to use of the same infusion set as the offending platelet aliquot. Figure 1 illustrates the event timelines. Figure 1 View largeDownload slide Timeline of events of transfusion-transmitted bacterial infection due to Klebsiella pneumoniae in an apheresis platelet collection and the three patient outcomes. Timeline expressed as hours since donor-initiated platelet apheresis collection. Figure 1 View largeDownload slide Timeline of events of transfusion-transmitted bacterial infection due to Klebsiella pneumoniae in an apheresis platelet collection and the three patient outcomes. Timeline expressed as hours since donor-initiated platelet apheresis collection. TTBI Cases: Transfusion Reaction Investigations Suspected transfusion reactions were not reported to the blood bank over the course of these events. The operating rooms (ORs) were closed over potential contamination concerns. The operating room charge nurse called the blood bank manager to discuss the OR closures and a rumor of contaminated blood products. This phone conversation, at 144 hours postcollection of the contaminated donation, was the first notification of a possible contamination, and investigation immediately ensued. The products were scrutinized, and a common donor identification number of transfused components was identified. The implicated units had been discarded and none remained to interrogate via culture given the delayed notification. The blood bank inventory was evaluated, and no additional products from the implicated donor were identified at that time. Donor Investigation The donor was a 56-year-old man and repeat apheresis platelet donor who had never been transfused. His medical history was unremarkable. He donated an apheresis platelet approximately 6 weeks prior without incident, and he reported feeling healthy on the day of the implicated donation. His blood pressure (120/78 mm Hg), heart rate (62 bpm), and temperature (36.4°C) were within normal ranges. The collection followed standard procedure, and there were no reported problems or nonconformances. The product was collected over a 94-minute period on an Amicus (Fresenius Kabi, Bad Homburg, Germany) machine. The unit type was A positive, and infectious disease testing was negative. At time 24 hours, the culture bottle was drawn per procedure. At time 48 hours, the BacT/ALERT system showed no growth, and the product was released to the blood bank. The product qualified as a single apheresis platelet component, which was later divided and transfused as four separate aliquots in the hospital blood bank. After the serious adverse events, the donor center contacted the donor to inquire about his health and explain the adverse transfusion events. He was encouraged to see his physician for evaluation of possible asymptomatic bacteremia, and blood and urine cultures were requested. He went to his clinician at time 192 hours. The physical examination was normal. A CBC revealed a WBC of 6.6 × 103/dL, and urine culture revealed more than 105 colony-forming units (CFUs)/mL of K pneumoniae. A blood culture was not obtained. His clinician prescribed ciprofloxacin. The donor has been permanently deferred from future donation, and previous donations were investigated with no adverse events identified. Bacteriologic Investigation When the blood bank was notified at time 144 hours of a possible transfusion reaction, appropriate microbiology workup of the residual product containers could not be performed as they had been discarded. Blood cultures of patients 1 and 3 were positive for K pneumoniae. An RBC unit from patient 3’s surgical case also grew K pneumoniae and Staphylococcus aureus (a suspected contaminant). Patient 2’s blood culture was negative, likely from timely coverage with antimicrobials to which K pneumoniae was determined to be susceptible. The donor’s urine culture grew K pneumoniae, but no blood culture was obtained. The BacT/ALERT culture bottle collected at the time of donation was negative at the expiration of the apheresis platelet product on the fifth day. At product release from the blood bank, the platelet aliquots successfully passed a visual inspection. The K pneumoniae isolates were genotyped using pulsed-field gel electrophoresis of DNA macrorestriction (XbaI). The isolates from the arterial blood of patients 1 and 3 were identical. The isolate from patient 3’s RBC bag and the donor’s urine were two to three bands different from each other and the identical blood strains. Per the clinical microbiology laboratory’s standard procedure, the interpretation was that the isolates were likely part of a sentinel microorganism clone Figure 2. Figure 2 View largeDownload slide Klebsiella pneumoniae DNA profiles by pulsed-field gel electrophoresis. Results interpretation: samples were probably all part of the same outbreak. The arterial blood from patient 3 and patient 1 has identical DNA band digestion by pulsed-field gel electrophoresis. The donor’s urine and the RBC bag from patient 3 differ by at least two bands (short dashed arrows). The donor’s urine and arterial blood from patient 3 differ by at least two bands (long dashed arrows). The RBC bag and arterial blood from patient 3 differ by at least two bands (short solid arrows). Figure 2 View largeDownload slide Klebsiella pneumoniae DNA profiles by pulsed-field gel electrophoresis. Results interpretation: samples were probably all part of the same outbreak. The arterial blood from patient 3 and patient 1 has identical DNA band digestion by pulsed-field gel electrophoresis. The donor’s urine and the RBC bag from patient 3 differ by at least two bands (short dashed arrows). The donor’s urine and arterial blood from patient 3 differ by at least two bands (long dashed arrows). The RBC bag and arterial blood from patient 3 differ by at least two bands (short solid arrows). Evaluation of Secondary Prospective Bacterial Culture Since implementation of the double culture protocol, 68 total alerted events were identified from the 25,177 platelets tested for a rate of 0.27%. Forty-eight (0.19% of total tested) were false positives with no growth in either the bottles or product. Fifteen (0.06%) were contaminants with growth in the bottle but no growth in the platelet product. Five true-positive alarms were detected (0.02%) with growth in both the bottle and product, with two instances of the second culture bottle (time 48 hours) being positive and the first culture bottle (time 24 hours) being negative (0.01%). The bacteria from our institution’s true-positive events were Streptococcus salivarius, Streptococcus viridans, Streptococcus mitis, and Propionibacterium acnes, with the latter two isolates detected only by the second culture bottle and missed by the first bottle Figure 3. Figure 3 View largeDownload slide Summary of positive BacT/ALERT (events) from 2011 to November 2016. Of the five true positives during this period, two were detected by the 48-hour sample but not by the 24-hour sample. Figure 3 View largeDownload slide Summary of positive BacT/ALERT (events) from 2011 to November 2016. Of the five true positives during this period, two were detected by the 48-hour sample but not by the 24-hour sample. Actions taken toward quality improvement are shown in Table 1. The TTBI risk mitigation strategies, including 24- and 48-hour BacT/ALERT, pan genera detection (PGD) testing at issue, and implementation of pathogen reduction technology along with associated costs are summarized in Table 2 and Table 3. No septic transfusion reactions have been identified since the TTBIs reported here. Table 1 Actions for Quality Improvement in Response to TTBI Casesa Actions Taken   Corrective or Preventive Action?b  Time of Implementation  Hemovigilance reporting education and training initiative  Corrective  Immediately  Alert blood bank when intracellular bacteria identified on peripheral blood smear of transfusion recipient  Corrective  Immediately  Increased sampling volume for prospective bacterial culture  Corrective  Within 3 months (once vendor could supply)  Secondary platelet culture at 48 hours  Corrective  Within days  Implementation of bacterial testing at issue  Corrective  5 years later after FDA draft guidance issued  Gradual implementation of pathogen-reduced platelet components  Corrective and preventive  5 years later after FDA draft guidance issued  Actions Taken   Corrective or Preventive Action?b  Time of Implementation  Hemovigilance reporting education and training initiative  Corrective  Immediately  Alert blood bank when intracellular bacteria identified on peripheral blood smear of transfusion recipient  Corrective  Immediately  Increased sampling volume for prospective bacterial culture  Corrective  Within 3 months (once vendor could supply)  Secondary platelet culture at 48 hours  Corrective  Within days  Implementation of bacterial testing at issue  Corrective  5 years later after FDA draft guidance issued  Gradual implementation of pathogen-reduced platelet components  Corrective and preventive  5 years later after FDA draft guidance issued  FDA, US Food and Drug Administration. aSince the reported transfusion-transmitted bacterial infection (TTBI) events, no additional suspected transfusion reactions reported to the transfusion service have been adjudicated as TTBIs. bPer ISO 9000, corrective action eliminates the cause of nonconformities to prevent recurrence, while preventive action determines and eliminates the causes of potential nonconformities (to prevent occurrence). View Large Table 2 Screening for Bacterial Contamination Performed on Nonpathogen-Reduced Platelets (7-Day Storage) Sample   Value  BacT/ALERT 24-hour sample (implemented prior to TTBIs)    Cost per test, $  15.50  BacT/ALERT 48-hour sample (implemented in 2011 after TTBIs)    Cost per test, $  15.50  BacT surveillance from 2011 to November 2016    True positives, total No.  5 of 25,177  True positives, caught by 48-hour sample and missed by 24-hour sample, No.  2 of 25,177  False positives, No.  48 of 25,177  Contaminants, No.  15 of 25,177  Units interdicted due to 48-hour sample, No.  2 or 25,177  Cost per unit interdicted due to 48-hour sample implementation, $  195,122  PGD testing (implemented September 2016)    Tests performed to date, No.  9,799  No. of units tested  6,259  Average No. of tests per unit  1.57  Cost per test, $  25  True positives, No.  0 of 9,799  False positives, No.  44 of 9,799a  Cost per interdicted unit due to PGD  No units interdicted since implementation  Cost to date, $  244,975  Average cost of BacT/ALERT and PGD testing per unit, $  70  Sample   Value  BacT/ALERT 24-hour sample (implemented prior to TTBIs)    Cost per test, $  15.50  BacT/ALERT 48-hour sample (implemented in 2011 after TTBIs)    Cost per test, $  15.50  BacT surveillance from 2011 to November 2016    True positives, total No.  5 of 25,177  True positives, caught by 48-hour sample and missed by 24-hour sample, No.  2 of 25,177  False positives, No.  48 of 25,177  Contaminants, No.  15 of 25,177  Units interdicted due to 48-hour sample, No.  2 or 25,177  Cost per unit interdicted due to 48-hour sample implementation, $  195,122  PGD testing (implemented September 2016)    Tests performed to date, No.  9,799  No. of units tested  6,259  Average No. of tests per unit  1.57  Cost per test, $  25  True positives, No.  0 of 9,799  False positives, No.  44 of 9,799a  Cost per interdicted unit due to PGD  No units interdicted since implementation  Cost to date, $  244,975  Average cost of BacT/ALERT and PGD testing per unit, $  70  PGD, pan genera detection; TTBI, transfusion-transmitted bacterial infection. aEight of 44 from recalled lot known to have a high false-positive rate. View Large Table 3 Pathogen-Reduced Platelets (5-Day Storage) Pathogen-Reduced Platelets   Value  Date implemented  September 21, 2016  Pathogen-reduced platelets, No.  2,908  Total collected platelet units, No.  5,492  Percentage inventory pathogen reduced  53  Additional cost per pathogen-reduced unit, $  97  Cost of pathogen reduction to date, $  282,076  Pathogen-Reduced Platelets   Value  Date implemented  September 21, 2016  Pathogen-reduced platelets, No.  2,908  Total collected platelet units, No.  5,492  Percentage inventory pathogen reduced  53  Additional cost per pathogen-reduced unit, $  97  Cost of pathogen reduction to date, $  282,076  View Large Discussion Platelet components are the most likely transfusion product to be contaminated by infectious agents due to required room temperature storage with constant agitation and a gas-permeable container.8 FDA-reported fatalities due to TTBIs vary from year to year, but they continue to occur (four reported in 2015), along with nonfatal septic transfusion reactions.5 Here, after experiencing three TTBIs (including two fatalities), we sought a comprehensive quality improvement approach with both corrective and preventive actions. The clinical features of TTBI include fever, chills, and hypotension, several of which were present in one or more of our patient cases; however, serious transfusion reactions such as TTBI are infrequent and can be difficult to identify clinically, especially in patients with complex medical conditions that manifest similar signs or symptoms. A retrospective pediatric review of electronic medical and transfusion records for acute transfusion reaction symptoms found that only four (3.4%) of 116 reportable acute transfusion reactions were reported.9 The events described here demonstrate the importance of expeditious reporting of suspected transfusion reactions to the transfusion service for evaluation by a transfusion medicine specialist and any subsequent necessary interventions (eg, rapid quarantine of co-components). After these serious adverse events, an educational initiative was undertaken to enhance suspected transfusion reaction reporting with a particular focus on anesthesia and nursing staff. An additional policy was adopted to alert the blood bank when intracellular bacteria are identified on peripheral blood smears from a transfused patient. Going forward, reporting rates of suspected transfusion reactions and classification data will continue to be monitored to measure the effectiveness of educational initiatives. In addition, timely feedback regarding delayed reporting, particularly for serious or potentially serious adverse events, will be provided. Other potential future directions include targeted chart audits to identify underreporting, which can be followed by constructive educational approaches as needed. Platelet components are more likely to be contaminated by Gram-positive than Gram-negative bacteria.3 While Gram positives are often contaminants from skin flora, both Gram-positive and Gram-negative organisms can cause severe infectious adverse events via transfusion. The causative organism of the three TTBIs was K pneumoniae. We postulated that since the donor’s urine culture and the patient’s bacterial isolates were part of the same sentinel clone, the lack of a positive BacT/ALERT culture was likely due to sampling error caused by a low bacterial burden at the time of sampling. The insufficient sensitivity illustrated by the TTBI cases spurred the corrective actions that followed. Measures to reduce risk, such as improved skin disinfection and implementation of new blood diversion devices, have helped the blood safety system but may be insufficient. Diversion of the first 10 to 40 mL of blood during collection has decreased contamination by more than 50%.8,10-13 Also, BacT/ALERT can detect 10 CFUs/mL and prevent release of 50% to 75% of contaminated platelet units.1-3,10 Subclinical infection of the donor and contamination during collection are thought to be the most frequent mechanisms of contamination despite these measures.10 Even with these more stringent precautions, the estimated bacterial contamination rate of platelets is high enough to cause concern because these events are often severe and platelet transfusion is a high-volume activity. Culture methods are extremely sensitive but can yield false-negative results due to sampling error.1,14 Previous studies have shown enhanced sensitivity when doubling sample volume as well as an improvement in confirmed positive rates due to the inclusion of anaerobic cultures.6,7 In 2017, McDonald15 reported a true-positive rate of 0.03% with a onetime 8-mL inoculation volume at 36 to 48 hours in BacT/ALERT aerobic and anaerobic culture. It has also been demonstrated that detection of K pneumoniae specifically may be improved if sampled on day 2 and cultured for 24 hours.10 Based on these data, the decision was made to implement these practices as corrective action. After implementation of increased sampling volume and secondary culture at 48 hours, five true-positive contaminated products were detected, two of which were only detected in the second bottle (48-hour sample). Therefore, two donations with the potential to cause TTBI were interdicted out of a total of 25,177 donations. The cost per interdicted unit in our hands due to 48-hour sampling was $195,122. While a day 3 culture has been suggested as a possible secondary prospective culture approach, it was operationally more feasible for us to implement a day 2 secondary culture prior to shipping platelet components.16 The implicated donation was collected using an Amicus (Fresenius Kabi) machine. A recent large retrospective study identified significantly higher rates of bacterially contaminated platelet donations as well as reported septic transfusion reactions associated with Amicus compared with Trima (Terumo BCT, Lakewood, CO) collections.17 The Amicus manufacturer stated it would take measures to improve safety with its software and the diversion collection process. While the data appeared to show a compelling association, whether the collection device type played any role in the cases discussed here is unknown. Bacterial testing at issue and pathogen reduction technology are other strategies to reduce bacterial contamination of platelet components. Despite the fact that some effective risk mitigation strategies are now standard and the initial corrective actions taken here likely added layers of safety, the FDA issued a draft guidance recommending testing at issue and/or use of pathogen reduction.18 While testing at issue can further prevent TTBI, pathogen reduction was also considered an effective option for true preventive action by also mitigating risk of nonbacterial transfusion-transmitted infection. Testing at issue was implemented in September 2016. Since implementation, PGD testing has not detected a confirmed culture-positive product (44 false positives of 9,799 total tests of 6,259 products). At $25 per test for PGD testing and $15.50 per unit for the 48-hour sampling, the added cost per unit is not insignificant for either measure. Pathogen reduction has been subsequently gradually implemented, and we currently use a mixed-platelet inventory of either pathogen-reduced (currently 53%) or standard platelets that are BacT tested at 24 and 48 hours along with PGD tested at issue. Pathogen-reduced platelets are $97 per unit and, in our hands, nonpathogen-reduced units with our current risk mitigation strategies are approximately $70 per unit. While it is currently not logistically feasible for us to have a 100% pathogen-reduced platelet inventory due to stringent procedural guard band requirements (in terms of volume and platelet count), inventory can likely be increased with optimized volume mitigation strategies. In conclusion, current TTBI risk mitigation strategies were felt to be insufficient in light of three severe cases, and opportunities for quality improvement were identified and implemented. The corrective and preventive actions taken here are expected to reduce the residual risk of TTBI at any institution but must be weighed against potential added costs, which may be significant. Acknowledgment: We thank Bryn McWhorter for technical assistance with this manuscript. References 1. Schmidt M, Hourfar MK, Nicol SB et al.   A comparison of three rapid bacterial detection methods under simulated real-life conditions. Transfusion . 2006; 46: 1367- 1373. Google Scholar CrossRef Search ADS PubMed  2. Niu MT, Knippen M, Simmons L et al.   Transfusion-transmitted Klebsiella pneumoniae fatalities, 1995 to 2004. Transfus Med Rev . 2006; 20: 149- 157. Google Scholar CrossRef Search ADS PubMed  3. Ramirez-Arcos S, DiFranco C, McIntyre T et al.   Residual risk of bacterial contamination of platelets: six years of experience with sterility testing. Transfusion . 2017; 57: 2174- 2181. Google Scholar CrossRef Search ADS PubMed  4. Jacobs MR, Good CE, Lazarus HM et al.   Relationship between bacterial load, species virulence, and transfusion reaction with transfusion of bacterially contaminated platelets. Clin Infect Dis . 2008; 46: 1214- 1220. Google Scholar CrossRef Search ADS PubMed  5. Food and Drug Administration. Fatalities reported to FDA following blood collection and transfusion annual summary for FY2015. https://www.fda.gov/downloads/BiologicsBloodVaccines/SafetyAvailability/ReportaProblem/TransfusionDonationFatalities/UCM518148.pdf. Accessed September 28, 2017. 6. Souza S, Bravo M, Poulin T et al.   Improving the performance of culture-based bacterial screening by increasing the sample volume from 4 mL to 8 mL in aerobic culture bottles. Transfusion . 2012; 52: 1576- 1582. Google Scholar CrossRef Search ADS PubMed  7. Benjamin RJ, McDonald CP; ISBT Transfusion Transmitted Infectious Disease Bacterial Workgroup. The international experience of bacterial screen testing of platelet components with an automated microbial detection system: a need for consensus testing and reporting guidelines. Transfus Med Rev . 2014; 28: 61- 71. Google Scholar CrossRef Search ADS PubMed  8. Klausen SS, Hervig T, Seghatchian J et al.   Bacterial contamination of blood components: Norwegian strategies in identifying donors with higher risk of inducing septic transfusion reactions in recipients. Transfus Apher Sci . 2014; 51: 97- 102. Google Scholar CrossRef Search ADS PubMed  9. Li N, Williams L, Zhou Z et al.   Incidence of acute transfusion reactions to platelets in hospitalized pediatric patients based on the US hemovigilance reporting system. Transfusion . 2014; 54: 1666- 1672. Google Scholar CrossRef Search ADS PubMed  10. Nussbaumer W, Allerstorfer D, Allersdorfer D et al.   Prevention of transfusion of platelet components contaminated with low levels of bacteria: a comparison of bacteria culture and pathogen inactivation methods. Transfusion . 2007; 47: 1125- 1133. Google Scholar CrossRef Search ADS PubMed  11. Walther-Wenke G, Schrezenmeier H, Deitenbeck R et al.   Screening of platelet concentrates for bacterial contamination: spectrum of bacteria detected, proportion of transfused units, and clinical follow-up. Ann Hematol . 2010; 89: 83- 91. Google Scholar CrossRef Search ADS PubMed  12. de Korte D, Marcelis JH, Verhoeven AJ et al.   Diversion of first blood volume results in a reduction of bacterial contamination for whole-blood collections. Vox Sang . 2002; 83: 13- 16. Google Scholar CrossRef Search ADS PubMed  13. Benjamin RJ, Kline L, Dy BA et al.   Bacterial contamination of whole-blood-derived platelets: the introduction of sample diversion and prestorage pooling with culture testing in the American Red Cross. Transfusion . 2008; 48: 2348- 2355. Google Scholar CrossRef Search ADS PubMed  14. Mertens G, Muylle L. False-positive and false-negative results of sterility testing of stored platelet concentrates. Transfusion . 1999; 39: 539- 540. Google Scholar CrossRef Search ADS PubMed  15. McDonald CP. Interventions implemented to reduce the risk of transmission of bacteria by transfusion in the English National Blood Service. Transfus Med Hemother . 2011; 38: 255- 258. Google Scholar CrossRef Search ADS PubMed  16. Bloch EM. Residual risk of bacterial contamination: what are the options? Transfusion . 2017; 57: 2289- 2292. Google Scholar CrossRef Search ADS PubMed  17. Eder AF, Dy BA, DeMerse B et al.   Apheresis technology correlates with bacterial contamination of platelets and reported septic transfusion reactions. Transfusion . 2017; 57: 2969- 2976. Google Scholar CrossRef Search ADS PubMed  18. Food and Drug Administration. Bacterial risk control strategies for blood collection establishments and transfusion services to enhance the safety and availability of platelets for transfusion. https://www.fda.gov/downloads/Guidances/Blood/UCM425952.pdf. Accessed September 26, 2017. © American Society for Clinical Pathology, 2018. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png American Journal of Clinical Pathology Oxford University Press

Quality Improvement After Multiple Fatal Transfusion-Transmitted Bacterial Infections

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Abstract

Abstract Objectives Transfusion-transmitted bacterial infection (TTBI) from platelet components is likely underrecognized and can be fatal. Twenty-four-hour prospective culture was felt to be insufficiently preventive after multiple TTBIs occurred and strategies to improve safety were sought. Methods Two fatal and one severe TTBIs occurred from a split-apheresis platelet donation contaminated with Klebsiella pneumoniae. Improvement opportunities were identified and corrective and preventive action (CAPA) followed. Results To mitigate bacterial contamination and improve detection sensitivity, additional prospective culture 48 hours postcollection was implemented. Since implementation, secondary cultures have caught two true positives (0.01%) missed by 24-hour culture. Bacterial testing at issue and pathogen reduction were later implemented as an added layer of safety. Conclusion While rare, TTBI is a prominent cause of morbidity and mortality from contaminated platelets. The approach to CAPA presented here may lower the risk of future transfusion-transmitted infections but must be weighed against potential added costs. Transfusion-transmitted bacterial infection, Quality improvement, Corrective and preventive action, Testing at issue, Pathogen reduction It is well documented that platelet components are the most common source of septic transfusion reactions given their room temperature storage conditions. Rates of contamination have been estimated from 1 in 1,000 to 10,000 units, usually from donor skin flora or occult bloodstream infection.1-3 Transfusion-transmitted bacterial infections (TTBIs) are likely underrecognized clinically, but fatalities continue to be reported to the US Food and Drug Administration (FDA) each year.4 In the United States, between 2011 and 2015, microbial-contaminated transfusion fatalities were the fourth most common cause of death, accounting for 10% of the total transfusion-related fatalities.5 Most fatal bacterially contaminated platelet units were due to Gram-negative bacteria, and one reported fatality from 2011 to 2015 was due to Klebsiella pneumoniae.5 While stringent requirements for bacterial detection of platelet products have been in place for many years, they are insufficient to prevent all potential TTBIs. Because apheresis platelet collections can yield multiple co-components, hemovigilance with timely reporting of suspected transfusion reactions can be critical for expeditious quarantining of any co-components remaining in inventory. To maximally prevent adverse outcomes from TTBI, a more comprehensive strategy may be undertaken. An approach to improve the sensitivity of bacterial detection is discussed here along with eventual implementation of testing at issue and pathogen reduction technology. Materials and Methods Three cases of TTBI from a single apheresis platelet donation contaminated with K pneumoniae occurred. TTBIs are considered serious adverse events that can be fatal (as demonstrated here). The clinical and laboratory characteristics were reviewed in detail. After identification and diagnosis, hemovigilance was examined to identify opportunities for improvement. The current hemovigilance process at our institution was examined first, and root cause analyses were performed subsequently. In addition to the current process, corrective action to further minimize TTBI risk and possible preventive action surrounding other potential infectious agents (viruses, parasites) was sought. First, an additional prospective culture protocol at 48 hours was implemented to identify bacterial contamination. Because platelet components are stored at room temperature, it was hypothesized that low-level contamination missed by the current prospective culture protocol would be caught by the additional 48-hour prospective culture along with greater sampling volumes as an approach to enhance detection sensitivity. The rationale for greater sampling volume was supported by previous studies showing increased sensitivity.6,7 Surveillance of secondary cultures was performed and utility evaluated. As a result of the TTBI events, the reporting donor center quickly implemented a double-culture protocol with the BacT/ALERT system (bioMérieux, Marcy-l’Étoile, France) in an attempt to increase sensitivity. Over approximately 5 years, a 10-mL aliquot was taken from each platelet donation at 24 hours postcollection for aerobic and anaerobic cultures, respectively, and another 10-mL aliquot for aerobic culture was obtained at time 48 hours. If no growth was detected in either culture at 56 hours after the donation, the product was released for transfusion. These bottles were incubated for the entire life of the product. Previously, 4-mL aliquots were used for an aerobic and anaerobic culture at time 24 hours and the product released at time 48 hours if cultures were negative. The secondary culture was a corrective action to mitigate the risk of a previously identified problem. Preventive action was subsequently pursued and the decision was made to implement pathogen reduction technology (Intercept; Cerus Corporation, Concord, CA) to mitigate the potential risk of problems that have not yet occurred (ie, transfusion-transmitted infections due to other infectious agents such as viruses and parasites). Transfusion reactions were reviewed after implementation of these processes. Results TTBI Cases: Brief Description The first patient received two apheresis platelet aliquots from the offending donation during surgery. K pneumoniae was identified by blood culture and peripheral smear. The patient developed lactic acidosis and disseminated intravascular coagulation (DIC) and ultimately died. The second patient received an apheresis platelet aliquot from the contaminated donation as an outpatient. During the infusion, the patient experienced vomiting and hypoxia, and acute lung injury was later identified. While blood cultures were negative, the patient was taking antimicrobials to which the offending bacterium was later found to be susceptible. After prolonged hospitalization, the patient survived. The third patient received an apheresis platelet aliquot of the contaminated product. The patient became frankly septic, and K pneumoniae was again identified. The patient developed multiorgan failure and died a few days later. K pneumoniae was also isolated from the RBC unit used to prime the extracorporeal life support (ECLS) machine likely due to use of the same infusion set as the offending platelet aliquot. Figure 1 illustrates the event timelines. Figure 1 View largeDownload slide Timeline of events of transfusion-transmitted bacterial infection due to Klebsiella pneumoniae in an apheresis platelet collection and the three patient outcomes. Timeline expressed as hours since donor-initiated platelet apheresis collection. Figure 1 View largeDownload slide Timeline of events of transfusion-transmitted bacterial infection due to Klebsiella pneumoniae in an apheresis platelet collection and the three patient outcomes. Timeline expressed as hours since donor-initiated platelet apheresis collection. TTBI Cases: Transfusion Reaction Investigations Suspected transfusion reactions were not reported to the blood bank over the course of these events. The operating rooms (ORs) were closed over potential contamination concerns. The operating room charge nurse called the blood bank manager to discuss the OR closures and a rumor of contaminated blood products. This phone conversation, at 144 hours postcollection of the contaminated donation, was the first notification of a possible contamination, and investigation immediately ensued. The products were scrutinized, and a common donor identification number of transfused components was identified. The implicated units had been discarded and none remained to interrogate via culture given the delayed notification. The blood bank inventory was evaluated, and no additional products from the implicated donor were identified at that time. Donor Investigation The donor was a 56-year-old man and repeat apheresis platelet donor who had never been transfused. His medical history was unremarkable. He donated an apheresis platelet approximately 6 weeks prior without incident, and he reported feeling healthy on the day of the implicated donation. His blood pressure (120/78 mm Hg), heart rate (62 bpm), and temperature (36.4°C) were within normal ranges. The collection followed standard procedure, and there were no reported problems or nonconformances. The product was collected over a 94-minute period on an Amicus (Fresenius Kabi, Bad Homburg, Germany) machine. The unit type was A positive, and infectious disease testing was negative. At time 24 hours, the culture bottle was drawn per procedure. At time 48 hours, the BacT/ALERT system showed no growth, and the product was released to the blood bank. The product qualified as a single apheresis platelet component, which was later divided and transfused as four separate aliquots in the hospital blood bank. After the serious adverse events, the donor center contacted the donor to inquire about his health and explain the adverse transfusion events. He was encouraged to see his physician for evaluation of possible asymptomatic bacteremia, and blood and urine cultures were requested. He went to his clinician at time 192 hours. The physical examination was normal. A CBC revealed a WBC of 6.6 × 103/dL, and urine culture revealed more than 105 colony-forming units (CFUs)/mL of K pneumoniae. A blood culture was not obtained. His clinician prescribed ciprofloxacin. The donor has been permanently deferred from future donation, and previous donations were investigated with no adverse events identified. Bacteriologic Investigation When the blood bank was notified at time 144 hours of a possible transfusion reaction, appropriate microbiology workup of the residual product containers could not be performed as they had been discarded. Blood cultures of patients 1 and 3 were positive for K pneumoniae. An RBC unit from patient 3’s surgical case also grew K pneumoniae and Staphylococcus aureus (a suspected contaminant). Patient 2’s blood culture was negative, likely from timely coverage with antimicrobials to which K pneumoniae was determined to be susceptible. The donor’s urine culture grew K pneumoniae, but no blood culture was obtained. The BacT/ALERT culture bottle collected at the time of donation was negative at the expiration of the apheresis platelet product on the fifth day. At product release from the blood bank, the platelet aliquots successfully passed a visual inspection. The K pneumoniae isolates were genotyped using pulsed-field gel electrophoresis of DNA macrorestriction (XbaI). The isolates from the arterial blood of patients 1 and 3 were identical. The isolate from patient 3’s RBC bag and the donor’s urine were two to three bands different from each other and the identical blood strains. Per the clinical microbiology laboratory’s standard procedure, the interpretation was that the isolates were likely part of a sentinel microorganism clone Figure 2. Figure 2 View largeDownload slide Klebsiella pneumoniae DNA profiles by pulsed-field gel electrophoresis. Results interpretation: samples were probably all part of the same outbreak. The arterial blood from patient 3 and patient 1 has identical DNA band digestion by pulsed-field gel electrophoresis. The donor’s urine and the RBC bag from patient 3 differ by at least two bands (short dashed arrows). The donor’s urine and arterial blood from patient 3 differ by at least two bands (long dashed arrows). The RBC bag and arterial blood from patient 3 differ by at least two bands (short solid arrows). Figure 2 View largeDownload slide Klebsiella pneumoniae DNA profiles by pulsed-field gel electrophoresis. Results interpretation: samples were probably all part of the same outbreak. The arterial blood from patient 3 and patient 1 has identical DNA band digestion by pulsed-field gel electrophoresis. The donor’s urine and the RBC bag from patient 3 differ by at least two bands (short dashed arrows). The donor’s urine and arterial blood from patient 3 differ by at least two bands (long dashed arrows). The RBC bag and arterial blood from patient 3 differ by at least two bands (short solid arrows). Evaluation of Secondary Prospective Bacterial Culture Since implementation of the double culture protocol, 68 total alerted events were identified from the 25,177 platelets tested for a rate of 0.27%. Forty-eight (0.19% of total tested) were false positives with no growth in either the bottles or product. Fifteen (0.06%) were contaminants with growth in the bottle but no growth in the platelet product. Five true-positive alarms were detected (0.02%) with growth in both the bottle and product, with two instances of the second culture bottle (time 48 hours) being positive and the first culture bottle (time 24 hours) being negative (0.01%). The bacteria from our institution’s true-positive events were Streptococcus salivarius, Streptococcus viridans, Streptococcus mitis, and Propionibacterium acnes, with the latter two isolates detected only by the second culture bottle and missed by the first bottle Figure 3. Figure 3 View largeDownload slide Summary of positive BacT/ALERT (events) from 2011 to November 2016. Of the five true positives during this period, two were detected by the 48-hour sample but not by the 24-hour sample. Figure 3 View largeDownload slide Summary of positive BacT/ALERT (events) from 2011 to November 2016. Of the five true positives during this period, two were detected by the 48-hour sample but not by the 24-hour sample. Actions taken toward quality improvement are shown in Table 1. The TTBI risk mitigation strategies, including 24- and 48-hour BacT/ALERT, pan genera detection (PGD) testing at issue, and implementation of pathogen reduction technology along with associated costs are summarized in Table 2 and Table 3. No septic transfusion reactions have been identified since the TTBIs reported here. Table 1 Actions for Quality Improvement in Response to TTBI Casesa Actions Taken   Corrective or Preventive Action?b  Time of Implementation  Hemovigilance reporting education and training initiative  Corrective  Immediately  Alert blood bank when intracellular bacteria identified on peripheral blood smear of transfusion recipient  Corrective  Immediately  Increased sampling volume for prospective bacterial culture  Corrective  Within 3 months (once vendor could supply)  Secondary platelet culture at 48 hours  Corrective  Within days  Implementation of bacterial testing at issue  Corrective  5 years later after FDA draft guidance issued  Gradual implementation of pathogen-reduced platelet components  Corrective and preventive  5 years later after FDA draft guidance issued  Actions Taken   Corrective or Preventive Action?b  Time of Implementation  Hemovigilance reporting education and training initiative  Corrective  Immediately  Alert blood bank when intracellular bacteria identified on peripheral blood smear of transfusion recipient  Corrective  Immediately  Increased sampling volume for prospective bacterial culture  Corrective  Within 3 months (once vendor could supply)  Secondary platelet culture at 48 hours  Corrective  Within days  Implementation of bacterial testing at issue  Corrective  5 years later after FDA draft guidance issued  Gradual implementation of pathogen-reduced platelet components  Corrective and preventive  5 years later after FDA draft guidance issued  FDA, US Food and Drug Administration. aSince the reported transfusion-transmitted bacterial infection (TTBI) events, no additional suspected transfusion reactions reported to the transfusion service have been adjudicated as TTBIs. bPer ISO 9000, corrective action eliminates the cause of nonconformities to prevent recurrence, while preventive action determines and eliminates the causes of potential nonconformities (to prevent occurrence). View Large Table 2 Screening for Bacterial Contamination Performed on Nonpathogen-Reduced Platelets (7-Day Storage) Sample   Value  BacT/ALERT 24-hour sample (implemented prior to TTBIs)    Cost per test, $  15.50  BacT/ALERT 48-hour sample (implemented in 2011 after TTBIs)    Cost per test, $  15.50  BacT surveillance from 2011 to November 2016    True positives, total No.  5 of 25,177  True positives, caught by 48-hour sample and missed by 24-hour sample, No.  2 of 25,177  False positives, No.  48 of 25,177  Contaminants, No.  15 of 25,177  Units interdicted due to 48-hour sample, No.  2 or 25,177  Cost per unit interdicted due to 48-hour sample implementation, $  195,122  PGD testing (implemented September 2016)    Tests performed to date, No.  9,799  No. of units tested  6,259  Average No. of tests per unit  1.57  Cost per test, $  25  True positives, No.  0 of 9,799  False positives, No.  44 of 9,799a  Cost per interdicted unit due to PGD  No units interdicted since implementation  Cost to date, $  244,975  Average cost of BacT/ALERT and PGD testing per unit, $  70  Sample   Value  BacT/ALERT 24-hour sample (implemented prior to TTBIs)    Cost per test, $  15.50  BacT/ALERT 48-hour sample (implemented in 2011 after TTBIs)    Cost per test, $  15.50  BacT surveillance from 2011 to November 2016    True positives, total No.  5 of 25,177  True positives, caught by 48-hour sample and missed by 24-hour sample, No.  2 of 25,177  False positives, No.  48 of 25,177  Contaminants, No.  15 of 25,177  Units interdicted due to 48-hour sample, No.  2 or 25,177  Cost per unit interdicted due to 48-hour sample implementation, $  195,122  PGD testing (implemented September 2016)    Tests performed to date, No.  9,799  No. of units tested  6,259  Average No. of tests per unit  1.57  Cost per test, $  25  True positives, No.  0 of 9,799  False positives, No.  44 of 9,799a  Cost per interdicted unit due to PGD  No units interdicted since implementation  Cost to date, $  244,975  Average cost of BacT/ALERT and PGD testing per unit, $  70  PGD, pan genera detection; TTBI, transfusion-transmitted bacterial infection. aEight of 44 from recalled lot known to have a high false-positive rate. View Large Table 3 Pathogen-Reduced Platelets (5-Day Storage) Pathogen-Reduced Platelets   Value  Date implemented  September 21, 2016  Pathogen-reduced platelets, No.  2,908  Total collected platelet units, No.  5,492  Percentage inventory pathogen reduced  53  Additional cost per pathogen-reduced unit, $  97  Cost of pathogen reduction to date, $  282,076  Pathogen-Reduced Platelets   Value  Date implemented  September 21, 2016  Pathogen-reduced platelets, No.  2,908  Total collected platelet units, No.  5,492  Percentage inventory pathogen reduced  53  Additional cost per pathogen-reduced unit, $  97  Cost of pathogen reduction to date, $  282,076  View Large Discussion Platelet components are the most likely transfusion product to be contaminated by infectious agents due to required room temperature storage with constant agitation and a gas-permeable container.8 FDA-reported fatalities due to TTBIs vary from year to year, but they continue to occur (four reported in 2015), along with nonfatal septic transfusion reactions.5 Here, after experiencing three TTBIs (including two fatalities), we sought a comprehensive quality improvement approach with both corrective and preventive actions. The clinical features of TTBI include fever, chills, and hypotension, several of which were present in one or more of our patient cases; however, serious transfusion reactions such as TTBI are infrequent and can be difficult to identify clinically, especially in patients with complex medical conditions that manifest similar signs or symptoms. A retrospective pediatric review of electronic medical and transfusion records for acute transfusion reaction symptoms found that only four (3.4%) of 116 reportable acute transfusion reactions were reported.9 The events described here demonstrate the importance of expeditious reporting of suspected transfusion reactions to the transfusion service for evaluation by a transfusion medicine specialist and any subsequent necessary interventions (eg, rapid quarantine of co-components). After these serious adverse events, an educational initiative was undertaken to enhance suspected transfusion reaction reporting with a particular focus on anesthesia and nursing staff. An additional policy was adopted to alert the blood bank when intracellular bacteria are identified on peripheral blood smears from a transfused patient. Going forward, reporting rates of suspected transfusion reactions and classification data will continue to be monitored to measure the effectiveness of educational initiatives. In addition, timely feedback regarding delayed reporting, particularly for serious or potentially serious adverse events, will be provided. Other potential future directions include targeted chart audits to identify underreporting, which can be followed by constructive educational approaches as needed. Platelet components are more likely to be contaminated by Gram-positive than Gram-negative bacteria.3 While Gram positives are often contaminants from skin flora, both Gram-positive and Gram-negative organisms can cause severe infectious adverse events via transfusion. The causative organism of the three TTBIs was K pneumoniae. We postulated that since the donor’s urine culture and the patient’s bacterial isolates were part of the same sentinel clone, the lack of a positive BacT/ALERT culture was likely due to sampling error caused by a low bacterial burden at the time of sampling. The insufficient sensitivity illustrated by the TTBI cases spurred the corrective actions that followed. Measures to reduce risk, such as improved skin disinfection and implementation of new blood diversion devices, have helped the blood safety system but may be insufficient. Diversion of the first 10 to 40 mL of blood during collection has decreased contamination by more than 50%.8,10-13 Also, BacT/ALERT can detect 10 CFUs/mL and prevent release of 50% to 75% of contaminated platelet units.1-3,10 Subclinical infection of the donor and contamination during collection are thought to be the most frequent mechanisms of contamination despite these measures.10 Even with these more stringent precautions, the estimated bacterial contamination rate of platelets is high enough to cause concern because these events are often severe and platelet transfusion is a high-volume activity. Culture methods are extremely sensitive but can yield false-negative results due to sampling error.1,14 Previous studies have shown enhanced sensitivity when doubling sample volume as well as an improvement in confirmed positive rates due to the inclusion of anaerobic cultures.6,7 In 2017, McDonald15 reported a true-positive rate of 0.03% with a onetime 8-mL inoculation volume at 36 to 48 hours in BacT/ALERT aerobic and anaerobic culture. It has also been demonstrated that detection of K pneumoniae specifically may be improved if sampled on day 2 and cultured for 24 hours.10 Based on these data, the decision was made to implement these practices as corrective action. After implementation of increased sampling volume and secondary culture at 48 hours, five true-positive contaminated products were detected, two of which were only detected in the second bottle (48-hour sample). Therefore, two donations with the potential to cause TTBI were interdicted out of a total of 25,177 donations. The cost per interdicted unit in our hands due to 48-hour sampling was $195,122. While a day 3 culture has been suggested as a possible secondary prospective culture approach, it was operationally more feasible for us to implement a day 2 secondary culture prior to shipping platelet components.16 The implicated donation was collected using an Amicus (Fresenius Kabi) machine. A recent large retrospective study identified significantly higher rates of bacterially contaminated platelet donations as well as reported septic transfusion reactions associated with Amicus compared with Trima (Terumo BCT, Lakewood, CO) collections.17 The Amicus manufacturer stated it would take measures to improve safety with its software and the diversion collection process. While the data appeared to show a compelling association, whether the collection device type played any role in the cases discussed here is unknown. Bacterial testing at issue and pathogen reduction technology are other strategies to reduce bacterial contamination of platelet components. Despite the fact that some effective risk mitigation strategies are now standard and the initial corrective actions taken here likely added layers of safety, the FDA issued a draft guidance recommending testing at issue and/or use of pathogen reduction.18 While testing at issue can further prevent TTBI, pathogen reduction was also considered an effective option for true preventive action by also mitigating risk of nonbacterial transfusion-transmitted infection. Testing at issue was implemented in September 2016. Since implementation, PGD testing has not detected a confirmed culture-positive product (44 false positives of 9,799 total tests of 6,259 products). At $25 per test for PGD testing and $15.50 per unit for the 48-hour sampling, the added cost per unit is not insignificant for either measure. Pathogen reduction has been subsequently gradually implemented, and we currently use a mixed-platelet inventory of either pathogen-reduced (currently 53%) or standard platelets that are BacT tested at 24 and 48 hours along with PGD tested at issue. Pathogen-reduced platelets are $97 per unit and, in our hands, nonpathogen-reduced units with our current risk mitigation strategies are approximately $70 per unit. While it is currently not logistically feasible for us to have a 100% pathogen-reduced platelet inventory due to stringent procedural guard band requirements (in terms of volume and platelet count), inventory can likely be increased with optimized volume mitigation strategies. In conclusion, current TTBI risk mitigation strategies were felt to be insufficient in light of three severe cases, and opportunities for quality improvement were identified and implemented. The corrective and preventive actions taken here are expected to reduce the residual risk of TTBI at any institution but must be weighed against potential added costs, which may be significant. Acknowledgment: We thank Bryn McWhorter for technical assistance with this manuscript. References 1. Schmidt M, Hourfar MK, Nicol SB et al.   A comparison of three rapid bacterial detection methods under simulated real-life conditions. Transfusion . 2006; 46: 1367- 1373. Google Scholar CrossRef Search ADS PubMed  2. Niu MT, Knippen M, Simmons L et al.   Transfusion-transmitted Klebsiella pneumoniae fatalities, 1995 to 2004. Transfus Med Rev . 2006; 20: 149- 157. Google Scholar CrossRef Search ADS PubMed  3. Ramirez-Arcos S, DiFranco C, McIntyre T et al.   Residual risk of bacterial contamination of platelets: six years of experience with sterility testing. Transfusion . 2017; 57: 2174- 2181. Google Scholar CrossRef Search ADS PubMed  4. Jacobs MR, Good CE, Lazarus HM et al.   Relationship between bacterial load, species virulence, and transfusion reaction with transfusion of bacterially contaminated platelets. Clin Infect Dis . 2008; 46: 1214- 1220. Google Scholar CrossRef Search ADS PubMed  5. Food and Drug Administration. Fatalities reported to FDA following blood collection and transfusion annual summary for FY2015. https://www.fda.gov/downloads/BiologicsBloodVaccines/SafetyAvailability/ReportaProblem/TransfusionDonationFatalities/UCM518148.pdf. Accessed September 28, 2017. 6. Souza S, Bravo M, Poulin T et al.   Improving the performance of culture-based bacterial screening by increasing the sample volume from 4 mL to 8 mL in aerobic culture bottles. Transfusion . 2012; 52: 1576- 1582. Google Scholar CrossRef Search ADS PubMed  7. Benjamin RJ, McDonald CP; ISBT Transfusion Transmitted Infectious Disease Bacterial Workgroup. The international experience of bacterial screen testing of platelet components with an automated microbial detection system: a need for consensus testing and reporting guidelines. Transfus Med Rev . 2014; 28: 61- 71. Google Scholar CrossRef Search ADS PubMed  8. Klausen SS, Hervig T, Seghatchian J et al.   Bacterial contamination of blood components: Norwegian strategies in identifying donors with higher risk of inducing septic transfusion reactions in recipients. Transfus Apher Sci . 2014; 51: 97- 102. Google Scholar CrossRef Search ADS PubMed  9. Li N, Williams L, Zhou Z et al.   Incidence of acute transfusion reactions to platelets in hospitalized pediatric patients based on the US hemovigilance reporting system. Transfusion . 2014; 54: 1666- 1672. Google Scholar CrossRef Search ADS PubMed  10. Nussbaumer W, Allerstorfer D, Allersdorfer D et al.   Prevention of transfusion of platelet components contaminated with low levels of bacteria: a comparison of bacteria culture and pathogen inactivation methods. Transfusion . 2007; 47: 1125- 1133. Google Scholar CrossRef Search ADS PubMed  11. Walther-Wenke G, Schrezenmeier H, Deitenbeck R et al.   Screening of platelet concentrates for bacterial contamination: spectrum of bacteria detected, proportion of transfused units, and clinical follow-up. Ann Hematol . 2010; 89: 83- 91. Google Scholar CrossRef Search ADS PubMed  12. de Korte D, Marcelis JH, Verhoeven AJ et al.   Diversion of first blood volume results in a reduction of bacterial contamination for whole-blood collections. Vox Sang . 2002; 83: 13- 16. Google Scholar CrossRef Search ADS PubMed  13. Benjamin RJ, Kline L, Dy BA et al.   Bacterial contamination of whole-blood-derived platelets: the introduction of sample diversion and prestorage pooling with culture testing in the American Red Cross. Transfusion . 2008; 48: 2348- 2355. Google Scholar CrossRef Search ADS PubMed  14. Mertens G, Muylle L. False-positive and false-negative results of sterility testing of stored platelet concentrates. Transfusion . 1999; 39: 539- 540. Google Scholar CrossRef Search ADS PubMed  15. McDonald CP. Interventions implemented to reduce the risk of transmission of bacteria by transfusion in the English National Blood Service. Transfus Med Hemother . 2011; 38: 255- 258. Google Scholar CrossRef Search ADS PubMed  16. Bloch EM. Residual risk of bacterial contamination: what are the options? Transfusion . 2017; 57: 2289- 2292. Google Scholar CrossRef Search ADS PubMed  17. Eder AF, Dy BA, DeMerse B et al.   Apheresis technology correlates with bacterial contamination of platelets and reported septic transfusion reactions. Transfusion . 2017; 57: 2969- 2976. Google Scholar CrossRef Search ADS PubMed  18. Food and Drug Administration. Bacterial risk control strategies for blood collection establishments and transfusion services to enhance the safety and availability of platelets for transfusion. https://www.fda.gov/downloads/Guidances/Blood/UCM425952.pdf. Accessed September 26, 2017. © American Society for Clinical Pathology, 2018. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

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American Journal of Clinical PathologyOxford University Press

Published: Apr 1, 2018

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