Abstract
Objective: We investigated the therapeutic effect of recombinant soluble thrombomodulin (rTM) in patients with sepsis who have disseminated intravascular coagulation (DIC).
Methods: The patients with sepsis who met the diagnostic criteria for acute DIC (JAAM) and showed a level of antithrombin (AT) lower than 70% were treated with AT products and Gabexate mesilate, and designated as the Control group. The septic DIC patients treated with rTM in addition to the above treatment were designated as TM group. Patients with severe liver dysfunction, severe bleeding tendency, or receiving other medications for DIC were excluded. The difference between TM and Control groups was investigated to see the effect of rTM by evaluating the clinical course through DIC score, and hemostatic and inflammatory markers.
Results: Twelve patients were included in the TM group, and 16 patients in the Control group. There were no differences in the APACHEII score, DIC score, or mortality between the groups. The effects of the rTM were as follows; 1) Patients in the TM group showed earlier DIC resolution at day 5 than Control at day 7. 2) Hypercoagulant state expressed by the increased levels of soluble fibrin monomer (SF) or thrombin-antithrombin complex (TAT) was improved more quickly in TM group compared with Control group. Because the levels of SF at day 3 and day 7 in TM group were lower than those in Control group, rTM may suppress thrombin production. 3) AT was more increased at day 3 after AT product administration in TM group compared to Control group, which also can be explained by suppression of thrombin production by rTM. 4) Increased levels of the complex of α2PI and plasmin (PIC), D-dimer, and fibrin/fibrinogen degradation product (FDP) were also improved earlier in TM group than Control group at day 7, suggesting the anti-thrombolytic effect of rTM. The inflammatory markers, TNF-α, IL-6, HMGB1 were decreased significantly at day 3 as compared with day 0 in TM group, but not in Control group, suggesting that rTM may act as an anti-inflammatory molecule.
Discussion: DIC was resolved more earlier in TM group than in Control group. rTM administration may preserve plasma AT and attenuate hypercogulable, hyperfibrinolytic and hyperinflammatory state in septic DIC through suppression of thrombin generation.
Conclusion: rTM may be beneficial in improving septic DIC via its anti-thrombogenic and anti-inflammatory properties.
