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Dear Editor, We read with interest the retrospective analysis by Hoshino and colleagues on prognostic biomarkers in patients with sepsis [1]. These authors evaluated various biomarkers of sepsis and coagulation/fibrinolysis markers in adult patients with sepsis. They showed that plasminogen activator inhibitor-1 (PAI-1) was the only independent predictive marker of 28-day mortality. In the commentary to the study by Hoshino et al., Iba and Thachil described a crucial role of the fibrinolytic system in the pathophysiology of sepsis, where multiple factors such as PAI-1, thrombin-activatable fibrinolysis inhibitor, and protein C participate in modulating the system [2]. They questioned why only PAI-1, but no other coagulation markers, was associated with mortality. They concluded that they recommend against one-point PAI-1 analysis for assessing coagulation/fibrinolytic systems, and were concerned that the findings by Hoshino and colleagues might mislead future studies. We wish to provide an alternative view in this correspondence. Inflammation and coagulation constitute two host defense systems with a complementary role against infection in sepsis. Depending on the severity of the systemic inflammatory reaction and the degree of involvement of coagulation derangement, sepsis exhibits various patterns of disease or organ dysfunction. In addition, the severity of inflammation and coagulopathy dramatically changes over time, and how these changes occur may affect the patients’ prognosis. Therefore, for precisely evaluating disease severity and progress at the time, what type of pathophysiological mechanism the markers of sepsis reflect and how it usually changes over time in the course of sepsis need to be understood. In the study by Hoshino et al. [1], the trends of coagulation/fibrinolysis markers over time between survivors and non-survivors in patients with sepsis are similar to the results of previous studies [3–5]. Notably, the time course of PAI-1 is consistent with our previous results, where a marked increase in its peak was observed in non-survivors on the day of admission, and this promptly decreased over a few days [5]. PAI-1 is a marker of inhibitory fibrinolysis and is excessively induced on the surface of endothelial cells by proinflammatory cytokines. This rapid increase in PAI-1 with a peak at around the onset of sepsis may suggest that PAI-1 reflects the severity of inflammation and coagulopathy in the early phase of sepsis. It might be, therefore, a reasonable finding that PAI-1 was a strong predictor of mortality at the time of ICU admission in Hoshino et al.’s study [1]. In Hoshino et al.’s study [1], their finding that only PAI-1 was significantly associated with mortality does not deny a relationship of other coagulation/fibrinolysis markers with mortality or with the pathophysiology of sepsis. In their study, logistic regression analysis was conducted for comparison of variables for the association with mortality, not for adjustment of baseline. Other markers, such as thrombin-antithrombin complex (TAT), protein C, and soluble fibrin, were associated with mortality in univariate analysis. Therefore, their results should be interpreted that there * Correspondence: k_koyama@jichi.ac.jp Division of Intensive Care, Department of Anesthesiology and Intensive Care Medicine, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan

Single measurement of plasminogen activator inhibitor-1 in sepsis: is it useful for evaluating the severity or prognosis of sepsis?