Related Experiment Videos
Tissue factor inhibition and clinical trial results of tissue factor pathway inhibitor in sepsis
1Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver 80220-3700, USA.
Abstract:
Tissue factor mediated pathways leading to microvascular thromboses and endothelial activation appear to play an important role in the development of multiple organ failure associated with severe sepsis. Tissue factor pathway inhibitor (TFPI) is an endogenous inhibitor of tissue factor associated coagulation cascades. In experimental models of severe sepsis, treatment with TFPI results in significant reduction in mortality. Similarly, a recently completed Phase II 210-patient study comparing placebo and infusions of TFPI showed trends toward a relative reduction in day 28 all-cause mortality in TFPI treated patients. These data suggest that coagulation cascades involving tissue factor contribute to organ dysfunction in critically ill septic patients. TFPI may be a useful therapy in improving outcome of severe sepsis.
Insights
Tissue factor pathway inhibitor (TFPI) may reduce mortality in severe sepsis by inhibiting coagulation cascades. Clinical trials show TFPI may improve outcomes in critically ill septic patients, suggesting its therapeutic potential.
Area of Science:
- Biochemistry
- Pathophysiology
- Pharmacology
Background:
- Severe sepsis is linked to microvascular thromboses and endothelial activation via tissue factor pathways.
- Tissue factor pathway inhibitor (TFPI) is a natural inhibitor of coagulation cascades.
- TFPI has shown promise in experimental sepsis models, reducing mortality.
Purpose of the Study:
- To evaluate the role of TFPI in severe sepsis.
- To assess the therapeutic potential of TFPI in improving outcomes for critically ill septic patients.
Main Methods:
- Experimental models of severe sepsis were used to test TFPI treatment.
- A Phase II clinical trial involving 210 patients compared TFPI infusions with placebo.
Main Results:
- TFPI treatment significantly reduced mortality in experimental sepsis models.
- The Phase II trial indicated a trend toward reduced 28-day all-cause mortality in TFPI-treated patients.
Conclusions:
- Coagulation cascades involving tissue factor contribute to organ dysfunction in severe sepsis.
- TFPI demonstrates potential as a therapeutic agent for improving outcomes in severe sepsis.