Platelet Collection Set Manufacturer Likely Source of Polymicrobial Transfusion-Transmitted Sepsis Cases

Findings from an extensive investigation performed by the Centers for Disease Control and Prevention and the Food and Drug Administration suggest that bacterial contamination found at a platelet collection set manufacturing facility appears to be the most likely source of multiple episodes of polymicrobial contamination of platelet components identified between May 2018 and December 2022. The findings were reported in an early release article from the CDC’s Emerging Infectious Diseases.

Whole-genome sequencing showed that environmental isolates found at the manufacturing facility were closely related genetically to patient and platelet isolates, indicating the manufacturer was the most probable source of recurrent polymicrobial contamination. The report recommends that clinicians maintain awareness of possible transfusion-transmitted sepsis even when bacterial risk control strategies are in place.

During the investigation, primary cultures of platelet collections by blood establishments before transfusion helped identify bacterial contamination with implicated strains, thus averting possible septic reactions. Despite the use of bacterial risk control strategies, including primary culture, secondary rapid testing, and pathogen reduction, seven cases of transfusion-transmitted sepsis were traced back to bacterial contamination of six platelet components from six different donors, resulting in three patient deaths.

Six of the seven (86%) cases were determined to have polymicrobial contamination; in one case, only Acinetobacter calcoaceticus-baumannii complex (ACBC) was isolated. Posttransfusion blood cultures from seven patients identified ACBC in six (86%), S. saprophyticus in four (57%) patients, Leclercia adecarboxylata in one (14%) patient and Enterobacter spp. in one (14%) patient. ACBC was identified in 6 out of 7 (86%) posttransfusion cultures, followed by S. saprophyticus in 6 out of 7 (86%), L. adecarboxylata in 3 out of 7 (43%), Enterobacter spp. in 1 out of 7 (14%), and Bacillus spp. in 1 out of 7 (14%) cultures.

FDA-required bacterial risk control strategies (primary culture, pathogen reduction or primary culture, and secondary rapid test) were performed before transfusion. Four (57%) of the implicated seven components were pathogen reduced and three (43%) were found to be negative following primary bacterial culture at least 24 hours after collection; two (67%) were determined to be negative following secondary rapid testing at day 4. Researchers noted that the manufacturer of the secondary rapid test used to detect bacterial contamination has since updated the device to improve detection of ACBC. A September 2021 Transfusion article confirms that the secondary rapid test was updated to enable Acinetobacter spp. detection to respond to morbidity and mortality events in 2018 and 2020 involving platelets contaminated with ACBC.

The researchers identified transfusion-transmitted sepsis via mandatory reporting of transfusion-related deaths to FDA. Cases were included if identical bacterial species were isolated from a transfused patient and a transfused platelet component, and if ACBC or S. saprophyticus — both uncommon species in transfusion-transmitted bacterial sepsis — was isolated from either a transfused patient or transfused platelet component.

The researchers also reviewed environmental surface sampling (conducted by CDC and local and state health departments) in blood establishments and health care facilities from which platelet components were collected, or in hospitals in which cases of transfusion-transmitted sepsis were reported, in five U.S. states (California, Connecticut, Massachusetts, North Carolina and Utah). As part of routine environmental monitoring, the manufacturer collected environmental isolates of the platelet collection set manufacturing facilities in Puerto Rico and the Dominican Republic.

The implicated platelets were collected by apheresis on the Amicus platform (Fenwal International, Inc.) and suspended in 65% platelet additive solution (InterSol Solution/Platelet Additive Solution 3 [PAS-C]; Fenwal International, Inc.) and 35% plasma. One blood establishment collected platelets from six different donors in six states.

The FDA investigation found that platelet collection sets were from a single manufacturer and were associated with multiple lot numbers of collection sets, saline, anti-coagulant solution and PAS-C manufactured between 2018 and 2020. The blood establishment took measures, including terminal cleaning, to reduce the risk of bacterial contamination in all platelet components. During a recent AABB Thursday Forum discussion, FDA confirmed that the agency does not recommend cleaning the external surface of platelet storage bags.

Current bacterial contamination mitigation strategies, such as secondary testing and pathogen reduction, are still considered to be highly effective in preventing contaminated platelet components from reaching patients. The investigators noted that of the roughly 2.1 million apheresis platelet units transfused in 2021, about 843,000 were pathogen reduced and roughly 1.2 million underwent various bacterial testing methods, underscoring the rarity of cases described in the study.

AABB encourages members to review Association Bulletin #21-02, which provides information that can help blood centers and transfusion services communicate and discuss mitigation strategies to support the continued availability of platelets for transfusion. Members should also consult AABB’s Bacterial Risk Reference Sheets for additional information.