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SUMMARY: OBJECTIVE We observed that many critically ill patients developed leukocytosis following blood transfusions. To validate this observation and to explore a possible mechanism, a prospective study was designed.DESIGN Prospective, noninterventional study.SETTING Surgical/medical intensive care unit in a university-affiliated community hospital.PATIENTS Consecutive patients who required packed red blood cells transfusion.INTERVENTIONS White blood cell count (mean ± sd) ×109/L before and 2, 4, 6, 12, and 24 hrs following transfusion of nonfiltered packed red cells was measured in 96 patients.MEASUREMENTS AND MAIN RESULTS Twenty patients were septic at the time of transfusion, whereas 76 were not. The incidence of post-transfusion leukocytosis in septic vs. nonseptic patients was 15% vs. 76%, respectively (p < .001). The white blood cell count in nonseptic patients increased from 14.3 ± 4.8 before transfusion to 19.5 ± 7.0 2 hrs following transfusion (p < .001) and returned to baseline in 24 hrs. In the septic group, no significant post-transfusion leukocytosis occurred. In 11 nonseptic patients requiring more than one unit of packed red cells, a significant increase in mean white blood cell count occurred 2 hrs after transfusion with nonfiltered packed red cells, whereas transfusion with prestorage-filtered packed red cells did not result in such an increase. Interleukin-8 concentrations (pg/mL) in stored nonfiltered packed red cells were significantly higher after 4 wks of storage (745.5 ± 710, p = .02) than at weeks 1 (61.2 ± 21.6) and 2 (59.3 ± 29). In the last 16 nonseptic patients, the units of nonfiltered packed red cells were assayed for interleukin-8 immediately before transfusion. Interleukin-8 concentrations were higher in units that caused leukocytosis in the recipients compared with those that did not (408.4 ± 202 vs. 65.1 ± 49, p = .02).CONCLUSIONS Transfusion of nonfiltered packed red cells, but not of prestorage-filtered packed red cells, may frequently cause an acute and transient leukocytosis in critically ill nonseptic patients. Interleukin-8 accumulating in stored nonfiltered packed red cells may play a role in this phenomenon. Recognition of post packed red cell transfusion leukocytosis may avoid unnecessary investigations and therapies in false suspicion of sepsis. [ABSTRACT FROM AUTHOR]