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Cecal Ligation Puncture Procedure
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Cecal Ligation Puncture Procedure

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Inflammation and coagulation: implications for the septic patient

R Phillip Dellinger1

  • 1Critical Care Section, . of Cardiovascular Diseases and Critical Care Medicine, Cooper Health System, Camden, New Jersey 08103, USA. dellinger-phil@cooperhealth.edu

Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America
|May 15, 2003
PubMed

Insights

Severe sepsis, a common and fatal condition, presents challenges for treatment. Antithrombotic therapy, like drotrecogin alpha (activated), shows promise in reducing sepsis-related mortality by targeting coagulation pathways.

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.

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