Plasminogen supplementation reverses fibrinolytic insufficiency in sepsis-induced disseminated intravascular coagulation: a pilot study.

PURPOSE: Sepsis-induced disseminated intravascular coagulation (DIC) is characterized by impaired fibrinolysis, partly due to neutrophil elastase-mediated plasminogen degradation. We aimed to evaluate whether plasminogen supplementation could restore fibrinolytic capacity in patients with sepsis-induced coagulopathy and in a murine model of septic DIC.

METHODS

60 patients with sepsis-induced coagulopathy were randomized to receive 12 mL/kg of placebo (NaCl 0.9%) or OctaplasLG®, a pathogen-inactivated pooled human plasma containing 2 µM plasminogen. Pre- and post-infusion levels of functional plasminogen, plasmin generation, and fibrinolysis markers (plasmin-antiplasmin complexes, plasminogen activator inhibitor-1, and tissue-type plasminogen activator) were measured. In parallel, in a sepsis-induced DIC model, transgenic TMpro/pro mice received either purified plasminogen or placebo. Functional plasminogen levels and plasmin generation were assessed via enzymatic assays.

RESULTS

In patients, baseline plasminogen and plasmin generation were significantly lower than in healthy controls. OctaplasLG® significantly increased functional plasminogen (+ 46 nM [-96; 118] vs. -84 [-180; 27] nM, p < 0.05) and improved plasmin generation (0.12 [-0.25; 1.27] vs. -0.36 [-1.58; 0.12] fmol, p < 0.05). No changes were observed in plasmin-antiplasmin, plasminogen activator inhibitor-1, or tissue-type plasminogen activator levels. A non-significant trend toward reduced mortality was noted in patients receiving OctaplasLG® (42.3% vs. 60.0%). Septic DIC-mice also exhibited reduced functional plasminogen (100 [66-126] vs. 295 [268-343] nM) and impaired plasmin generation (1.8 [1.4-2.1] vs. 3.0 [2.8-3.3] fmol, p < 0.05), which were restored after plasminogen supplementation (plasminogen: 346 [287; 360] nM; plasmin generation: 4.1 [3.7; 5.5] fmol).

CONCLUSION

Plasminogen supplementation restores fibrinolytic capacity, supporting its therapeutic potential in sepsis-induced DIC.