Combined therapy with antithrombin and recombinant human soluble thrombomodulin in patients with severe sepsis and disseminated intravascular coagulation

Objective: This study was performed in order to investigate the effects of combined therapy with antithrombin (AT) products and recombinant human soluble thrombomodulin (rTM) in patients with severe sepsis and disseminated intravascular coagulation (DIC) based on a retrospective historical cohort analysis.<BR>Methods: Diagnoses of DIC were made according to the criteria of acute DIC of the Japan Association of Acute Medicine. We examined 111 patients with severe sepsis diagnosed with DIC who were admitted to the intensive care unit and treated with AT products for anticoagulant therapy. The patients were divided into two groups: 51 patients received rTM for six days in addition to AT products (combination group), and 60 patients received AT products only, without rTM (control group). Changes in the coagulation parameters, DIC scores, and sequential organ failure assessment (SOFA) scores that occurred during the treatment were compared between the two groups. Furthermore, the survival outcomes of the patients at 28 days were evaluated by using the Kaplan-Meier method.<BR>Results: Before treatment, the platelet counts were significantly lower, and both the systemic inflammatory response syndrome (SIRS) positive scores and SOFA scores were significantly higher in the patients in the combination group. However, there were no differences between the two groups regarding the other parameters. During the treatment, no differences were observed between the two groups regarding the changes of PT ratios, fibrinogen levels, or AT activity levels were detected. However, statistically significant improvements were seen in the platelet counts, D-dimer test results, SIRS positive scores, and DIC scores for the patients in the combination group. The patients receiving combined therapy also showed significant improvements in SOFA scores. There were no differences between the two groups in the frequency of bleeding complications. The survival outcomes were significantly better for the patients in the combination group than for those in the control group (28 day survival rates: 86.3% versus 60%, p=0.0016). Significant improvements were only observed in the severely ill patients, such as those with acute physiology and chronic health evaluation (APACHE) II scores > 25 or AT activity levels < 50%. A multivariate analysis indicated the baseline AT activity levels and the administration of rTM to be independent beneficial factors associated with the 28-day survival rates.<BR>Conclusion: The combined therapy with AT and rTM showed a superior efficacy in the treatment of septic DIC, with improvements observed in coagulation parameters, and organ failure rates, and survival rates. This therapy is therefore considered to be a new and effective strategy for treating severe cases of the septic DIC.