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Sepsis-Associated DIC with Decreased Levels of Antithrombin and Fibrinogen is the Target for Combination Therapy with
Hideo Wada1, Kazuo Kawasugi2, Goichi Honda3
1Department of General Medicine, Mie Prefectural General Medical Center, Mie, Japan.
Insights
Disseminated intravascular coagulation (DIC) patients with low antithrombin and fibrinogen levels face worse outcomes. Combination therapy with antithrombin and thrombomodulin benefits infection-based DIC, improving survival rates.
Area of Science:
- Hematology
- Critical Care Medicine
Background:
- Disseminated intravascular coagulation (DIC) is a complex condition with variable pathophysiology and outcomes.
- Anticoagulant therapy benefits in DIC are subtype-specific, necessitating targeted treatment strategies.
Purpose of the Study:
- To identify patient subgroups who benefit from combination therapy with thrombomodulin and antithrombin.
- To evaluate the efficacy of combined antithrombin and thrombomodulin treatment in different DIC subtypes.
Main Methods:
- Analysis of 2,839 patients from thrombomodulin postmarketing surveillance data.
- Stratification of patients into four groups based on antithrombin and fibrinogen levels.
- Examination of additive effects of antithrombin on thrombomodulin therapy.
Main Results:
- Patients with low antithrombin/low fibrinogen exhibited higher DIC scores, SOFA scores, and mortality.
- Combination therapy significantly improved survival compared to thrombomodulin monotherapy.
- Therapeutic benefit of combination therapy was observed exclusively in infection-based DIC.
Conclusions:
- DIC patients with low antithrombin/low fibrinogen are at high risk for poor outcomes.
- Combination therapy with antithrombin and thrombomodulin is a viable option for infection-based DIC with these low levels.
- Targeted combination therapy can improve survival in specific, high-risk DIC populations.
Abstract:
Background Disseminated intravascular coagulation (DIC) is not a homogeneous condition, but rather includes heterogeneous conditions, and its pathophysiology and outcome vary considerably depending on the background. Although anticoagulant therapy is expected to be of benefit in the treatment of DIC, previous studies have suggested that the benefits are limited only to a specific subtype. Objects The purpose of this study was to identify the group that would benefit from combination therapy using thrombomodulin/antithrombin. Methods The data from 2,839 patients registered in the postmarketing surveillance of thrombomodulin were evaluated. The patients were divided into four groups depending on antithrombin and fibrinogen levels, and the additive effects of antithrombin on thrombomodulin were examined in the groups. Results The DIC score, Sequential Organ Failure Assessment score, and mortality were significantly higher in the DIC group with low-antithrombin/low-fibrinogen than in the DIC groups without either low antithrombin or low fibrinogen. The survival curve was significantly higher in DIC patients with combination therapy than in patients treated with thrombomodulin monotherapy, but this effect was seen only in patients with infection-based DIC. Conclusion DIC patients with low-antithrombin/low-fibrinogen risk poor outcomes, but they can be the target of combination therapy with antithrombin and thrombomodulin as long as the DIC is due to infection.
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