December 22, 2022
FDA is updating the communication first issued on April 16, 20191, and reissued on December 2, 20212, to inform blood establishments and transfusion services on the investigation of septic transfusion reactions from apheresis platelets contaminated with Acinetobacter species and certain other bacterial species seen in combination. Since 2018, FDA and the Centers for Disease Control and Prevention (CDC) have worked collaboratively to investigate these reports, including those described in publications3-6.
Summary of the Issue
Since 2018, FDA is aware of a total of 7 septic transfusion reactions (from 6 total donations) involving either Acinetobacter spp., Staphylococcus saprophyticus, Leclercia adecarboxylata, or combinations thereof, where additional genetic testing of isolates by the CDC found with high probability that the organisms were related and had a potential common source. These cases occurred in multiple states, and the implicated components were subject to various bacterial risk mitigation strategies including bacterial culture and/or secondary rapid testing prior to release, or processing with an FDA-approved pathogen reduction device prior to transfusion. FDA also received additional reports of positive bacterial cultures during routine testing of units that were not transfused where the same organisms were also identified. Several of these isolates showed a genetic match to isolates from the clinical cases of septic reactions, supporting the conclusion that the contamination events appear to be from a potential common source prior to additional testing or pathogen reduction, and not from contamination after distribution of the final component. In addition, environmental monitoring of the facility where apheresis collection set solutions were manufactured identified bacteria that were genetically matched to isolates from the clinical cases of septic reactions.
Throughout the investigation, FDA has interacted with blood establishments, the manufacturer of the platelet collection and storage system, as well as manufacturers of other related products, including bacterial testing devices and pathogen reduction devices. The implicated components included units prepared in platelet additive solution, units prepared in 100% plasma, units not treated with pathogen reduction devices, and units treated with pathogen reduction devices. Among the septic reaction cases that were genetically matched, the platelet components were all manufactured using blood collection and storage systems and solutions from a single manufacturer. FDA continues to conduct inspections of the manufacturer to ensure control of the manufacturing process and to maintain sterility of the collection sets and solutions. At this time, the strategies to assure the bacterial safety of platelet components recommended in FDA guidance7 remain acceptable.
Recommendations to Blood Establishments and Transfusion Services
These unusual cases demonstrate that it is important for blood establishments and transfusion services to continue to recognize the risk of bacterial contamination of platelets, including in bacterially tested and pathogen-reduced platelet components. Signs and symptoms of potential septic transfusion reactions include fever, chills, hypotension, or unexplained tachycardia. Suspected reactions should be immediately reported to the transfusion service and blood supplier. Blood establishments and transfusion services must conduct and record a thorough investigation of reported septic transfusion reactions and notify FDA as soon as possible when a complication of transfusion is confirmed to be fatal (21 CFR 606.170).
Blood establishments and transfusion services are also encouraged to contact FDA if they identify suspected septic transfusion reactions of platelets involving polymicrobial contamination, or contamination with Acinetobacter spp., Staphylococcus saprophyticus, or Leclercia adecarboxylata, and report the cases via MedWatch (https://www.fda.gov/Safety/MedWatch/default.htm). For additional information regarding CDC sepsis prevention and control efforts, please refer to https://www.cdc.gov/sepsis/prevention/index.html.
- U.S. Food and Drug Administration. Important Information for Blood Establishments and Transfusion Services Regarding Acinetobacter sp. Contamination of Platelets for Transfusion. 2019. Available: https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/important-information-blood-establishments-and-transfusion-services-regarding-acinetobacter-sp
- U.S. Food and Drug Administration. Important Information for Blood Establishments and Transfusion Services Regarding Acinetobacter sp. Contamination of Platelets for Transfusion. 2021. Available: https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/important-information-blood-establishments-and-transfusion-services-regarding-bacterial
- Nevala-Plagemann C, Powers P, Mir-Kasimov M, Rose R. A Fatal Case of Septic Shock Secondary to Acinetobacter Bacteremia Acquired from a Platelet Transfusion. Case Rep Med 2019; 2019: 3136493.
- Jones SA, Jones JM, Leung V, et al. Sepsis Attributed to Bacterial Contamination of Platelets Associated with a Potential Common Source - Multiple States, 2018. MMWR Morb Mortal Wkly Rep 2019; 68(23): 519-23.
- Fridey JL, Stramer SL, Nambiar A, et al. Sepsis from an apheresis platelet contaminated with Acinetobacter calcoaceticus/baumannii complex bacteria and Staphylococcus saprophyticus after pathogen reduction. Transfusion 2020; 60(9): 1960-9.
- Fadeyi EA, Wagner SJ, Goldberg C, et al. Fatal sepsis associated with a storage container leak permitting platelet contamination with environmental bacteria after pathogen reduction. Transfusion 2021; 61(2): 641-8.
- U.S. 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. 2020. Available: https://www.fda.gov/media/123448/download