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Disseminated Intravascular Coagulation: An Update on Pathogenesis, Diagnosis, and Therapeutic Strategies
Chrysoula Papageorgiou1, Georges Jourdi2,3, Eusebe Adjambri4
1Service Anesthésie, Réanimation Hôpital Tenon, Hôpitaux Universitaires Est Parisien, Assistance Publique Hôpitaux de Paris, Paris, France.
Insights
Disseminated intravascular coagulation (DIC) is a life-threatening condition requiring treatment of the underlying cause. While some therapies show promise, clinical trials specifically for DIC are limited, necessitating further research.
Area of Science:
- Hematology
- Critical Care Medicine
- Pharmacology
Background:
- Disseminated intravascular coagulation (DIC) is a critical condition involving widespread coagulation activation, leading to organ dysfunction and hemorrhage.
- DIC is triggered by various conditions, including sepsis, cancer, trauma, and obstetric emergencies.
- Effective treatment hinges on addressing the underlying disorder and managing coagulation activation and bleeding risks.
Purpose of the Study:
- To review current therapeutic strategies for disseminated intravascular coagulation (DIC).
- To assess the efficacy and safety of investigational treatments for DIC based on available clinical trial data.
- To highlight the limitations in clinical research for DIC and identify areas for future investigation.
Main Methods:
- Review of published phase III clinical trials investigating treatments for sepsis-associated DIC.
- Analysis of studies evaluating antithrombin (AT), activated protein C (APC), tissue factor pathway inhibitor (TFPI), and thrombomodulin (TM).
- Examination of data on the efficacy and safety of other anticoagulants and blood product transfusions in DIC.
Main Results:
- Activated protein C (APC) showed a survival benefit in severe sepsis with DIC but increased bleeding risk, leading to market withdrawal.
- Antithrombin (AT) did not reduce mortality in severe sepsis, though subgroup analysis suggested potential benefit in DIC.
- Recombinant TFPI and thrombomodulin (TM) have demonstrated promising results in preliminary studies.
- Efficacy and safety of unfractionated heparin, low-molecular-weight heparin, platelet, or clotting factor concentrates in DIC remain unassessed.
Conclusions:
- Treatment of the underlying disorder is paramount in managing DIC.
- While some agents like TFPI and TM show promise, robust clinical trial data specifically for DIC is scarce.
- Further research is needed to establish optimal therapeutic strategies and assess the safety and efficacy of various interventions for DIC.
Abstract:
Disseminated intravascular coagulation (DIC) is an acquired clinicobiological syndrome characterized by widespread activation of coagulation leading to fibrin deposition in the vasculature, organ dysfunction, consumption of clotting factors and platelets, and life-threatening hemorrhage. Disseminated intravascular coagulation is provoked by several underlying disorders (sepsis, cancer, trauma, and pregnancy complicated with eclampsia or other calamities). Treatment of the underlying disease and elimination of the trigger mechanism are the cornerstone therapeutic approaches. Therapeutic strategies specific for DIC aim to control activation of blood coagulation and bleeding risk. The clinical trials using DIC as entry criterion are limited. Large randomized, phase III clinical trials have investigated the efficacy of antithrombin (AT), activated protein C (APC), tissue factor pathway inhibitor (TFPI), and thrombomodulin (TM) in patients with sepsis, but the diagnosis of DIC was not part of the inclusion criteria. Treatment with APC reduced 28-day mortality of patients with severe sepsis, including patients retrospectively assigned to a subgroup with sepsis-associated DIC. Treatment with APC did not have any positive effects in other patient groups. The APC treatment increased the bleeding risk in patients with sepsis, which led to the withdrawal of this drug from the market. Treatment with AT failed to reduce 28-day mortality in patients with severe sepsis, but a retrospective subgroup analysis suggested possible efficacy in patients with DIC. Clinical studies with recombinant TFPI or TM have been carried out showing promising results. The efficacy and safety of other anticoagulants (ie, unfractionated heparin, low-molecular-weight heparin) or transfusion of platelet concentrates or clotting factor concentrates have not been objectively assessed.
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