Association between thrombomodulin and high mobility group box 1 in sepsis patients

World J Crit Care Med. 2020 Oct 18;9(4):63-73. doi: 10.5492/wjccm.v9.i4.63.

Abstract

Background: High mobility group box 1 (HMGB1) has been studied as a molecule associated with severe outcomes in sepsis and thrombomodulin (TM) seems to decrease HMGB1 activity.

Aim: To investigate the role of the thrombomodulin/high mobility group box 1 (T/H) ratio in patients with sepsis and their association with their clinic, testing the hypothesis that higher ratios are associated with better outcomes.

Methods: Twenty patients diagnosed with sepsis or septic shock, according to the 2016 criteria sepsis and septic shock (Sepsis-3), were studied. Patients were followed until they left the intensive care unit or until they achieved 28 d of hospitalization (D28). The following clinical outcomes were observed: Sequential Organ Failure Assessment (SOFA) score; Need for mechanical pulmonary ventilation; Presence of septic shock; Occurrence of sepsis-induced coagulopathy; Need for renal replacement therapy (RRT); and Death.

Results: The results showed that patients with SOFA scores greater than or equal to 12 points had higher serum levels of TM: 76.41 ± 29.21 pg/mL vs 37.41 ± 22.55 pg/mL among those whose SOFA scores were less than 12 points, P = 0.003. The T/H ratio was also higher in patients whose SOFA scores were greater than or equal to 12 points, P = 0.001. The T/H ratio was, on average, three times higher in patients in need of RRT (0.38 ± 0.14 vs 0.11 ± 0.09), P < 0.001.

Conclusion: Higher serum levels of TM and, therefore, higher T/H ratio in the first 24 h after the diagnosis of sepsis were associated with more severe disease and the need for renal replacement therapy, while those with better clinical outcomes and those who were discharged before D28 showed a tendency for lower T/H ratio values.

Keywords: High mobility group box 1; Mechanical ventilation; Renal replacement therapy; Sepsis; Septic shock; Thrombomodulin.