THROMBOMODULIN IN INTENSIVE-CARE PATIENTS

Objective: Changes of endothelial-related coagulation was studied in intensive care patients. Design: Descriptive, prospective. Setting: Clinical investigation, intensive care unit of an university hospital. Patients: 40 consecutive critically ill patients with severe trauma (n = 20) or postoperative complications (n = 20) were studied. 14 patients suffered from sepsis, 12 patients suffered from acute renal failure. Interventions: 12 patients with acute renal failure were continuously hemofiltrated. All patients were on continuous sedation (fentanyl and midazolam) and mechanical ventilation. Measurements: In addition to standard coagulation variables, thrombomodulin (TM), protein C and protein S as well as thrombin/antithrombin III (TAT) plasma concentrations were measured from arterial blood samples using enzyme-linked, immuno-sorbent assays (ELISA). Measurements were carried out on the day of admission (trauma patients) or on the day of diagnosis of sepsis and during the next 4 days. Main results: Throughout the entire investigation period, TM plasma concentrations in patients with sepsis (baseline: 90 +/- 25 mu g/l, 4th day: 152 +/- 28 mu g/l) were significantly higher than in non-septic patients (baseline: 60 +/- 29 mu g/l 4th day: 42 +/- 15 mu g/l). 15 of the 40 patients died within or after the end of the investigation period. TM plasma concentrations of survivors were lower (maximum: 63 +/- 18 mu g/l) than in the non-survivors (maximum: 159 +/- 22 mu g/l) (p < 0.05). Hemofiltered patients showed higher TM plasma levels, which further increased during the hemofiltration procedure. Protein C and (free) protein S were without significant group differences. TAT plasma levels were elevated above normal in ail patients (no group differences). Conclusions: Besides plasmatic and platelet-related coagulation, endothelium-associated coagulation appears to be also important for maintenance of hemostasis. TM plasma concentrations were elevated in all our critically ill patients, particularly when sepsis was evident. This appears to be most likely due to endothelial membrane damage with increased release of membrane-bound TM into the circulating blood in these patients. The importance of the elevated plasma levels of circulating soluble TM on hemostasis in these patients is an ongoing debate and warrants further studies.