Changes in fibrinolysis and severity of organ failure in sepsis: a prospective observational study using point-of-care test--ROTEM

Abstract

Purpose: We hypothesized that the thromboelastometry (ROTEM; Pentapharm GmbH, Munich, Germany) fibrinolysis parameter "maximum lysis" (ML) would have an independent inverse association with the severity of organ failure in sepsis.

Methods: Selected adult patients with sepsis (n = 77) were recruited within 24 hours of antibiotic commencement. Patients with Sequential Organ Failure Assessment score higher than 1 (n = 57) were followed for 72 hours. Prothrombin fragments 1 + 2, plasminogen activator inhibitor-1 (aPAI-1), ROTEM, and routine coagulation tests were measured daily along with Sequential Organ Failure Assessment scores.

Results: The activity of functional aPAI-1 increased with increasing severity of organ failure (P = .01) and was higher as compared with healthy controls (95% confidence interval, -65.4 to -29.9; P < .001). There was a decreasing trend in ML with increased organ failure (P = .001); however, there was no trend in d-dimer. Among all tests, only the lower ML (ß = -0.38, P < .001) and higher international normalized ratio (INR; ß = 0.32, P = .002) values significantly contributed to greater severity of organ failure (R(2) = 0.35, F2,73 = 19.29, P < .001). Despite an increase in INR, the prothrombin fragment remained unchanged (P = .89). Strong correlations were observed between early (24 hours) increase in fibrinolysis and recovery of organ failures for 48 hours (ML: r = 0.679, P = .001; aPAI-1: r = 0.694, P < .001).

Conclusions: Lower ML and higher INR values predicted greater severity of organ failure at presentation. Further studies are required, as ROTEM could aid selection of patients and guide interventions aimed at fibrinolysis in severe sepsis.

Keywords: Coagulation; Fibrinolysis; Plasminogen activator inhibitor-1; ROTEM; Sepsis; Thromboelastometry.