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The effect of antithrombin added to recombinant human-soluble thrombomodulin for severe community-acquired pneumonia-associated disseminated intravascular coagulation: a retrospective cohort study using a nationwide inpatient database.

ABSTRACT: Background:Studies showed potential benefits of recombinant human-soluble thrombomodulin (rhTM) and antithrombin for treating sepsis associated disseminated intravascular coagulation. However, benefits of their combination have been inconclusive. Methods:Using a nationwide inpatient database in Japan, we performed propensity-score matched analyses to compare outcomes between rhTM combined with antithrombin and rhTM alone for severe community-acquired pneumonia associated disseminated intravascular coagulation from July 2010 to March 2015. The outcomes included in-hospital mortality and requirement of red cell transfusion. Results:Propensity score matching created 189 pairs of patients who received rhTM combined with antithrombin or rhTM alone within 2 days of admission. There was no significant difference between the two groups for in-hospital mortality (40.2% vs. 45.5%). Patients treated with rhTM and antithrombin were more likely to require red cell transfusion than those treated with rhTM alone (37.0% vs. 25.9%). Conclusions:Compared with rhTM alone, combination of rhTM with antithrombin for severe community-acquired pneumonia-associated disseminated intravascular coagulation may be ineffective for reducing mortality and may increase bleeding.

SUBMITTER: Suzuki J

PROVIDER: S-EPMC6958595 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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The effect of antithrombin added to recombinant human-soluble thrombomodulin for severe community-acquired pneumonia-associated disseminated intravascular coagulation: a retrospective cohort study using a nationwide inpatient database.

Suzuki Jun J Sasabuchi Yusuke Y Hatakeyama Shuji S Matsui Hiroki H Sasahara Teppei T Morisawa Yuji Y Yamada Toshiyuki T Yasunaga Hideo H

Journal of intensive care 20200113

<h4>Background</h4>Studies showed potential benefits of recombinant human-soluble thrombomodulin (rhTM) and antithrombin for treating sepsis associated disseminated intravascular coagulation. However, benefits of their combination have been inconclusive.<h4>Methods</h4>Using a nationwide inpatient database in Japan, we performed propensity-score matched analyses to compare outcomes between rhTM combined with antithrombin and rhTM alone for severe community-acquired pneumonia associated dissemina ...[more]

PMID: 31956416

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Project description:The thrombomodulin (TM)/activated protein C (APC) system plays an important role in maintaining the homeostasis of thrombosis and hemostasis and maintaining vascular integrity in vivo. TM expressed on vascular endothelium binds to thrombin, forming a 1:1 complex and acts as an anticoagulant. In addition, the thrombin-TM complex activates protein C to produce APC, which inactivates factors VIIIa and Va in the presence of protein S, thereby inhibiting further thrombin formation. Intriguingly, APC possesses anti-inflammatory as well as cytoprotective activities. Moreover, the extracellular domain of TM also possesses APC-independent anti-inflammatory and cytoprotective activities. Of note, the TM/APC system is compromised in disseminated intravascular coagulation (DIC) caused by sepsis due to various mechanisms, including cleavage of cell-surface TM by exaggerated cytokines and proteases produced by activated inflammatory cells. Thus, it is reasonable to assume that reconstitution of the TM/APC system by recombinant proteins would alleviate sepsis and DIC. On the basis of the success of the Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) trial, the FDA approved the use of recombinant human APC (rhAPC) for severe sepsis patients in 2002. However, subsequent clinical trials failed to show clinical benefits for rhAPC, and an increased incidence of hemorrhage-related adverse events was noted, which prompted the industry to withdraw rhAPC from the market. On the other hand, recombinant human soluble TM (rTM) has been used for treatment of individuals with DIC since 2008 in Japan, and a phase III clinical trial evaluating the efficacy of rTM in severe sepsis patients with coagulopathy is now ongoing in the USA, South America, Asia, Australia, European Union, and other countries. This review article discusses the molecular mechanisms by which the TM/APC system produces anticoagulant as well as anti-inflammatory and cytoprotective activities in septic DIC patients.

Dataset Information

The effect of antithrombin added to recombinant human-soluble thrombomodulin for severe community-acquired pneumonia-associated disseminated intravascular coagulation: a retrospective cohort study using a nationwide inpatient database.

Publications

The effect of antithrombin added to recombinant human-soluble thrombomodulin for severe community-acquired pneumonia-associated disseminated intravascular coagulation: a retrospective cohort study using a nationwide inpatient database.

Similar Datasets

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