Inflammation and coagulation: implications for the septic patient

Area of Science:

• Critical care medicine
• Hematology
• Pathophysiology of sepsis

Background:

• Severe sepsis, characterized by acute organ dysfunction, is a leading cause of mortality and imposes a substantial economic burden.
• Current therapeutic strategies primarily focus on managing inflammation, but have shown limited success in reducing morbidity and mortality.
• The intricate link between inflammation and coagulation in sepsis is increasingly recognized, with sepsis-associated coagulopathy being nearly universal.

Purpose of the Study:

• To review the pathophysiological and clinical significance of the relationship between coagulation and inflammation in severe sepsis.
• To discuss the efficacy of antithrombotic-targeted therapies in managing severe sepsis.
• To examine the outcomes of clinical trials investigating antithrombotic interventions for severe sepsis.

Main Methods:

• Literature review of preclinical and clinical studies on sepsis, inflammation, coagulation, and antithrombotic therapies.
• Analysis of the role of recombinant human activated protein C (drotrecogin alpha [activated]) as a pioneering antithrombotic treatment.
• Discussion of the pathophysiological mechanisms linking coagulation and inflammation in sepsis.

Main Results:

• Preclinical studies suggested antithrombotic therapy could reduce sepsis-related morbidity and mortality.
• Recombinant human activated protein C (drotrecogin alpha [activated]) was the first antithrombotic agent to demonstrate a significant reduction in 28-day all-cause mortality in severe sepsis patients.
• Clinical trials of antithrombotic therapy have yielded both positive and negative results, highlighting the complexity of this approach.

Conclusions:

• Antithrombotic-targeted therapy represents a promising strategy for severe sepsis, distinct from anti-inflammatory approaches.
• Understanding the interplay between coagulation and inflammation is crucial for developing effective sepsis treatments.
• Further research and clinical trials are warranted to optimize antithrombotic interventions for severe sepsis.