Intensive care medicine · 2026
Plasminogen supplementation reverses fibrinolytic insufficiency in sepsis-induced disseminated intravascular coagulation: a pilot study.
СтатьяРандомизированное исследованиеНазвание и аннотация: Перевод в очереди
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Tschirhart Marine, Curtiaud Anaïs, Abou Rjeily Ramy, Merdji Hamid, Demiselle Julien, Severac François, Guerin Daniel, Caçao Micael, El Ghazouani Fatiha, Angles-Cano Eduardo, Toti Florence, Meziani Ferhat, Helms Julie
Аннотация
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.
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.