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Clinical experience with antithrombin III concentrates in critically ill patients with sepsis and multiple organ
Abstract:
Despite improvements in critical care medicine and the development and aggressive use of potent broad-spectrum anti-microbial agents, mortality due to severe sepsis has not changed during the recent years and still comes to 35% to 45%. For quite a long time our understanding of the pathophysiology of sepsis was mainly focused on endotoxin and proinflammatory cytokines like tumor necrosis factor or interleukin-1. Now it is generally accepted that many signs and symptoms of sepsis are not directly mediated by cytokines but are transmitted through other mediator systems. The coagulation system comes into play especially when the septic process progresses to malperfusion and organ failure. Antithrombin III is an important inhibitor of the intrinsic, extrinsic and common pathway of coagulation. Recently, evidence has been accumulating that there is an additional anti-inflammatory potential of the drug. Currently there are several clinical trials ongoing to investigate whether this effect is of clinical relevance in the treatment of patients with severe sepsis.
Insights
Severe sepsis mortality remains high despite advances. Antithrombin III, a coagulation inhibitor, shows potential anti-inflammatory effects, with ongoing trials investigating its clinical relevance in sepsis treatment.
Area of Science:
- Critical care medicine
- Immunology
- Hematology
Background:
- Severe sepsis mortality rates persist between 35-45% despite advancements in critical care and antimicrobial therapies.
- Traditional understanding of sepsis pathophysiology focused on endotoxins and pro-inflammatory cytokines.
- Emerging evidence suggests sepsis symptoms are mediated by systems beyond cytokines, including the coagulation cascade.
Purpose of the Study:
- To explore the role of the coagulation system in sepsis progression, particularly in cases of malperfusion and organ failure.
- To investigate the potential anti-inflammatory properties of Antithrombin III beyond its anticoagulant function.
- To assess the clinical relevance of Antithrombin III in severe sepsis treatment through ongoing clinical trials.
Main Methods:
- Review of current understanding of sepsis pathophysiology.
- Analysis of the role of Antithrombin III as a coagulation inhibitor.
- Monitoring of ongoing clinical trials evaluating Antithrombin III in severe sepsis.
Main Results:
- The coagulation system is implicated in sepsis progression, especially with malperfusion and organ failure.
- Accumulating evidence suggests Antithrombin III possesses anti-inflammatory potential.
- Clinical trials are currently underway to determine the therapeutic significance of this effect.
Conclusions:
- Antithrombin III's established role in coagulation inhibition may be complemented by significant anti-inflammatory effects.
- Further clinical investigation is crucial to establish Antithrombin III as a relevant therapeutic agent for severe sepsis.
- The evolving understanding of sepsis pathophysiology highlights the importance of exploring multifaceted therapeutic targets.