Thrombin generation in severe sepsis

Introduction: Hemostasis and inflammation are two tightly interrelated systems in the host's response to infection. Thrombin generation in sepsis plays a crucial role in enhancing and modulation of inflammation. The present study aimed to investigate the course of thrombin generation in patients with severe sepsis, and its correlation with outcome.

Materials and methods: Thrombin generation was measured in platelet-poor plasma from 32 healthy controls and 75 patients with severe sepsis using the commercially available Calibrated Automated Thrombography. Samples were taken within 24 hours of the diagnosis of severe sepsis (t1) as well as on day 2 (t2), day 3 or 4 (t3) and between day 6 to 8 (t4), while this was done only once in healthy controls. The assay was run with and without the addition of thrombomodulin. Clinical data were also collected at the same time points.

Results: Except for endogenous thrombin potential, there was significant difference between patients and controls regarding peak thrombin, lag time and time to thrombin peak. Twelve patients (16%) died in the ICU. There was no significant difference in endogenous thrombin potential between survivors and non-survivors of sepsis. Thrombin peak was higher in survivors than non-survivors at all time points, with a significant difference at t2 and t4. The lag time and time to thrombin peak were shorter in non-survivors than in survivors at t1 and t3.

Conclusions: While thrombin peak shows a positive correlation with survival, the lag phase and time to thrombin peak may be signs of impending DIC. The endogenous thrombin potential does not have any prognostic importance.