Related Experiment Video
Updated: Feb 26, 2026
A Fibrin-Enriched and tPA-Sensitive Photothrombotic Stroke Model
Published on: June 4, 2021
Plasminogen supplementation reverses fibrinolytic insufficiency in sepsis-induced disseminated intravascular
Marine Tschirhart1, Anaïs Curtiaud1,2,3, Ramy Abou Rjeily4
1INSERM (French National Institute of Health and Medical Research) UMR 1260, Regenerative Nanomedicine (RNM), Strasbourg, France.
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.
Related Concept Videos
01:16Clot Retraction and Fibrinolysis
01:29Venous Thrombosis III: Interprofessional Care
01:30Anticoagulant Drugs: Low-Molecular-Weight Heparins
01:20Extrinsic and Intrinsic Pathways of Hemostasis
The Extrinsic Pathway
The extrinsic pathway of coagulation is typically initiated by tissue damage that exposes blood to tissue factor (TF), a protein released by the damaged tissue cells outside the blood vessels—this interaction with TF triggers biochemical reactions involving specific clotting factors. The key player here is Factor VII, which...
01:29Pulmonary Embolism II: Diagnostic Studies and Interprofessional Care
01:22Formation of the Platelet Plug
As the injured blood vessel contracts, endothelial cells undergo contraction, revealing collagen fibers in the basement membrane and underlying connective tissue. Furthermore, the plasma membrane of endothelial cells becomes adhesive, preparing the site for platelet adhesion. Platelets...