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Novel approaches to the management of disseminated intravascular coagulation
M Levi1, E de Jonge, T van der Poll
1Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, The Netherlands.
Insights
Disseminated intravascular coagulation (DIC) causes organ failure through fibrin deposition. Novel treatments targeting coagulation activation show promise in experimental and early clinical studies for managing this critical condition.
Area of Science:
- Hematology
- Pathophysiology
- Critical Care Medicine
Background:
- Disseminated intravascular coagulation (DIC) involves systemic activation of coagulation and fibrin deposition.
- DIC is associated with significant morbidity and mortality, often leading to multiple organ failure.
Purpose of the Study:
- To determine if fibrin deposition in DIC contributes to multiple organ failure.
- To review the pathogenesis of DIC.
- To explore current and future therapeutic strategies for DIC.
Main Methods:
- Systematic review of published articles.
- Inclusion of experimental animal models of DIC.
- Inclusion of clinical studies in patients with DIC.
Main Results:
- DIC is strongly linked to increased morbidity and mortality.
- Pathogenesis involves cytokine-mediated coagulation activation via tissue factor/factor VIIa.
- Impaired fibrinolysis due to plasminogen activator inhibitor-1 enhances fibrin deposition.
Conclusions:
- Treating the underlying disorder is primary in DIC management.
- Inhibiting coagulation activation (e.g., tissue factor inhibition, restoring anticoagulant pathways) is a promising therapeutic strategy.
- While controlled trial data is limited, novel approaches like antithrombin or protein C concentrate administration are under investigation.
Objective:
Disseminated intravascular coagulation (DIC) is a syndrome characterized by systemic intravascular activation of coagulation, leading to widespread deposition of fibrin in the circulation. We addressed the issue of whether there is evidence that this fibrin deposition contributes to multiple organ failure. We also explored the current knowledge on the pathogenesis of DIC and reviewed current and future treatment for DIC.
Data Sources:
We searched and reviewed published articles on experimental studies of DIC models in animals and clinical studies in patients with DIC.
Data Synthesis:
There is ample experimental and clinical evidence that DIC contributes to morbidity and mortality. Recent knowledge on important pathogenetic mechanisms that may lead to DIC has resulted in novel preventive and therapeutic approaches to patients with DIC. Although the trigger for the activation of the coagulation system may vary depending on the underlying condition, it is usually mediated by several cytokines. Thrombin generation proceeds via the (extrinsic) tissue factor/factor VIIa route and simultaneously occurring depression of inhibitory mechanisms, such as antithrombin III and the protein C-protein S system. Also, impaired fibrin degradation, because of high circulating levels of plasminogen activator inhibitor, type 1, contributes to enhanced intravascular fibrin deposition.
Conclusions:
Although the cornerstone of DIC management is the specific and vigorous treatment of the underlying disorder, strategies aimed at inhibiting coagulation activation may theoretically be justified. Such strategies have been found to be beneficial in experimental and initial clinical studies. These strategies, which follow from our current understanding of the pathophysiology of DIC, involve inhibition of tissue factor-mediated activation of coagulation or restoration of physiologic anticoagulant pathways by means of the administration of antithrombin concentrate or (activated) protein C concentrate. Although no complete evidence from controlled clinical trials is available for most of the proposed therapeutic interventions, these novel strategies are being studied.