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Pathogenesis and treatment of disseminated intravascular coagulation in the septic patient
1Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Insights
Sepsis-related disseminated intravascular coagulation (DIC) increases mortality and organ dysfunction. Current treatments like antithrombin and activated protein C show promise, with future therapies exploring combination approaches for effective DIC reversal.
Area of Science:
- Critical Care Medicine
- Hematology
- Pathophysiology
Background:
- Sepsis incidence and complications remain high despite advanced care.
- Disseminated intravascular coagulation (DIC) is a frequent, high-mortality complication of sepsis.
- DIC correlates with organ dysfunction, driven by cytokine-induced procoagulant states and factor consumption.
Purpose of the Study:
- To review the pathophysiology of sepsis-induced DIC.
- To discuss current and emerging therapeutic strategies for DIC.
- To highlight the role of antithrombin and activated protein C in severe sepsis.
Main Methods:
- Literature review of sepsis and DIC pathophysiology.
- Analysis of clinical trials on novel therapeutic agents.
- Examination of molecular mechanisms in DIC development and treatment.
Main Results:
- Cytokine release in sepsis promotes intravascular fibrin deposition.
- Bleeding in later DIC stages results from clotting factor depletion.
- Antithrombin and activated protein C supplementation are supported by recent trials for severe sepsis DIC.
Conclusions:
- Therapeutic strategies target multiple stages of the DIC molecular cascade.
- Ongoing studies explore novel treatments, including combination therapies.
- Future efforts aim for prompt and successful DIC reversal through combined agents.
Abstract:
The incidence of sepsis and complications stemming from septicemia has remained constant in recent years despite improved levels of monitoring and care. Disseminated intravascular coagulation (DIC), a syndrome that occurs frequently in septic patients, is associated with increased mortality. Organ dysfunction is also a common sequela that is strongly correlated with DIC. Cytokines released early in the course of sepsis stimulate a procoagulant state that causes development of intravascular fibrin deposition. In a later stage of DIC, bleeding may occur in parallel because of consumption of clotting factors and inhibitors. Therapeutic strategies to attenuate or reverse these conditions have focused on multiple stages of the molecular cascade of events, including preventing cytokine induction, inhibiting coagulation processes, and promoting fibrinolysis. Recent clinical trials have supported the use of antithrombin and activated protein C supplementation in DIC associated with severe sepsis. Studies of other novel therapeutic avenues are still ongoing. Future efforts may be directed at combining 2 or more agents to achieve prompt and successful reversal of DIC.
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