Zero tolerance

B lood transfusion will never be completely safe, although tremendous improvements have been made in the past 10 years, through improved screening technologies and hemovigilance. In recent years defining the acceptable level of transfusion risk, and the provision of resources to achieve the defined levels, has been a largely political process. The move from storing blood in glass bottles to plastic packs in the early 1950s greatly reduced the incidence of posttransfusion bacterial infection. For 4°C stored red cell (RBC) products, sepsis remains a rare event. The introduction of storage at 22°C for platelets (PLTs) in the early 1970s by the late Scott Murphy and colleagues, as forewarned at the time, led to an increased rate of posttransfusion bacterial infection, particularly when the shelf life of such products was briefly extended beyond 5 days. With improvements to the methods for detecting the major transfusiontransmitted virus infections of concern, bacteria now account for the majority of transfusion-transmitted infections. By use of sensitive tests for the presence of bacteria, approximately 400 per million PLTs tested are found to be contaminated although most of these are at a level which will cause little or no harm to patients. After much debate, bacterial screening of PLT products was introduced in the United States in March 2004 after earlier implementation in some European countries. (AABB Standard 5.1.5.1. states: “The blood bank or transfusion service shall have methods to limit and detect bacterial contamination in all platelet components. Standard 5.6.2 applies [skin disinfection].” All AABB accredited blood banks were required to meet Standard 5.1.5.1 by March 1, 2004.) With the agreement of the FDA, through the PASSPORT scheme, the option exists to reextend PLT shelf life to 7 days. This scheme, which depends on bacterial testing by both aerobic and anaerobic methods at 24 hours with an additional 24-hour quarantine and retesting at outdate (7 days), has the advantage of defining an acceptable risk, in this case “no worse than the current bacterial risk for 5-day stored platelets,” estimated by the FDA to be around 100 per million doses (1 in 10,000). These statements refer to the rate of test-reactive units rather than the subset of stored PLTs that cause actual clinical problems. As with any screening assay concerns relate to the sensitivity and specificity. Recent reports(and C.V. Prowse, J. AuBuchon, and S. Wendel on behalf of the BEST Collaborative and ISBT Transfusion Transmitted Infection Subcommittee, bacterial testing practices survey 2004, unpublished) have shown that in combination with improved donor skin disinfection and diversion of the first few milliliters of donated blood, testing of PLTs with culture methods can prevent a significant number of bacterially infective PLTs from entering the blood supply (Table 1). Problems remain with the rate of false-positive tests, however, which leads to the discard of valuable product, and occasional test-negative units, which cause infection (false negatives). Evidence from the robust Canadian hemovigilance system records that diversion and testing has reduced the number of PLT-related posttransfusion infections by more than 70 percent, while surveillance in the United States suggests a 75 percent reduction in clinically evident bacteremia. A recent editorial in TRANSFUSION and a number of recent reviews have itemized the outcomes of such studies and the effects of the variable growth of bacterial species on test outcomes, together with their dependency on choice of assay method (including the choice of whether to undertake both aerobic and anaerobic assays if culturing), sampling time, sampled volume, the impact of retesting at later storage times, and the consequences for blood bank stocks, outdate rates, and age at issue. For the purposes of this commentary, it is sufficient to emphasize that the more serious clinical sequelae of transfusing contaminated PLTs have been associated with species that are largely aerobic and multiply fast, that European experience is that slow-growing contaminants may only become test-positive at a stage when up to 50 percent of units have already been transfused, and that sepsis and death still occur, albeit at a much reduced rate, even when a robust bacterial testing system is implemented (Table 1). Retesting, or use of anaerobic as well as aerobic tests, has obvious financial implications. The ideal solution would be to have a sensitive and rapid point-of-issue bacterial detection test. Such tests are in development by a number of companies and beg the question of what sensitivity is required. It is generally accepted that initial bacterial levels in infected units are of the order of 1 to 10 per mL (300-3000 per adult dose) and need to increase around 10,000-fold to have a clinical impact. In March 2007, one company announced that they have applied to the FDA for licensure of an assay with a sensitivity of approximately 10 to 10 bacteria per mL and an assay turnaround time of 30 minutes (license submitted March 15, 2007, to the FDA for 30-minute assay from Verax Pan Genera Detection based on the detection TRANSFUSION 2007;47:1106-1109.