Anticoagulation Therapy Using rh-Thrombomodulin and/or Antithrombin III Agent is Associated With Reduction in in-Hospital Mortality in Septic Disseminated Intravascular Coagulation: A Nationwide Registry Study

Tanaka, Keiko; Takeba, Jun; Matsumoto, Hironori; Ohshita, Muneaki; Annen, Suguru; Moriyama, Naoki; Nakabayashi, Yuki; Aibiki, Mayuki

doi:10.1097/shk.0000000000001230

Cited by 17 publications

(24 citation statements)

References 32 publications

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“…Furthermore, the ISTH-DIC patients in this study were more likely to have more severe APACHE II scores greater than or equal to 30 (data not shown). As we (12) and others (3,22) have reported previously, anticoagulation therapy could be more effective for septic DIC patients with higher severity, such as the ISTH-DIC patients in this study. However, as the lower panel of Table 3 shows, when only ISTH-DIC patients were considered, there were no statistically signi cant differences in in-hospital mortality rate among the three treatment-protocol groups.…”

Section: Rate Of Anti-coagulation Therapy Administration In Each Groupsupporting

confidence: 66%

“…In this study, we have clearly shown that differences in institutional policies regarding the administration of anti-coagulation treatments for septic DIC, are associated with differences in in-hospital mortality rate (HMR) and in adjusted HRs of HMR, especially between the DO-TX and NO-TX groups of patients with septic DIC. This nding appears to support the use of anticoagulants such as rh-TM or AT concentrates (12) for septic DIC with MOF.…”

Section: Discussionmentioning

confidence: 52%

“…Even non-DIC subjects (n=2513) were required to have this information. As a result, the number of patients in each DIC criteria category differs from that in our previous paper using the same database (12).…”

Section: Patient Selection and Data Collectionmentioning

confidence: 80%

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Institutional Anticoagulation Protocol for Septic DIC is Associated with Differences in In-Hospital Mortality. J-SEPTIC DIC STUDY (A Nationwide Registry Study)

Tanaka

Matsumoto

Ohshita

et al. 2020

Preprint

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Background: We analyzed data from Japanese nationwide registry study of severe sepsis/septic shock to determine the influence of institutional treatment protocol, which has not been evaluated, on in-hospital mortality rate in septic DIC. Methods: From among all sepsis patients (n=3193), we selected those (n=1856) diagnosed with DIC according to the JAAM criteria, then divided them into three groups depending on DIC treatment protocol: patients admitted to hospitals providing basically no anti-coagulation therapy (NO-TX group: n=287); those admitted to hospitals routinely providing such treatment (anti-thrombin concentrate and/or rh-thrombomodulin or other anti-coagulants such as heparin/heparinoids: DO-TX group: n=1202); and those admitted to hospitals providing treatment at the discretion of the physician-in-charge (DEP-TX group: n=446). Results: In DIC patients only, in-hospital mortality was much higher in the NO-TX group (46.2%) than in the DO-TX group (34.1%) despite comparable APACHE II scores. The hazard ratio (HR) of mortality was much lower in the DO-TX group (0.76, 95% CI: 0.61-0.96) than in the NO-TX group (set at 1.0). When non-DIC subjects whose records contained complete information on JAAM and ISTH scores were also included (n=2513), however, different treatment protocols were no longer associated with differences in HR. Nevertheless, in-hospital mortality rates still differed among the three groups even after non-DIC patients were included. Conclusions: Thus, the present results support the use of anti-coagulation treatments for septic DIC and suggest that outcomes are affected by other institutional factors besides anti-coagulation protocol, such as an institutional approach to sepsis. The mechanisms underlying this effect should be clarified.

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Section: Rate Of Anti-coagulation Therapy Administration In Each Groupsupporting

confidence: 66%

Section: Discussionmentioning

confidence: 52%

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Institutional Anticoagulation Protocol for Septic DIC is Associated with Differences in In-Hospital Mortality. J-SEPTIC DIC STUDY (A Nationwide Registry Study)

Tanaka

Matsumoto

Ohshita

et al. 2020

Preprint

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“…Although a recent study suggested that rhTM with or without AT might be associated with better prognosis in the patients with sepsis-induced DIC compared with other DIC treatments [20], the study did not investigate whether rhTM with AT was associated with lower mortality compared with rhTM alone. On the other hand, our results suggest that combination therapy with rhTM and AT may be an ineffective therapeutic approach for reducing mortality and increase bleeding in patients with DIC caused by severe community-acquired pneumonia.…”

Section: Discussionmentioning

confidence: 99%

“…Antithrombin (AT) is also used as an anticoagulant in patients with sepsis-associated DIC, and rhTM is often used with AT for treatment of sepsis-associated DIC in Japan [16][17][18][19], and AT added to rhTM may reduce mortality for patients with sepsis induced DIC [20]. One previous study showed that AT added to rhTM was associated with lower mortality [19].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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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 inhospital 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.

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Anticoagulant therapy for septic coagulopathy and disseminated intravascular coagulation: where do KyberSept and SCARLET leave us?

Wiedermann¹

2020

Acute Medicine & Surgery

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The use of antithrombin and thrombomodulin to restore impaired anticoagulant pathways in septic coagulopathy has been shown to significantly increase the resolution rate of disseminated intravascular coagulation. In KyberSept and SCARLET, two large, international, randomized controlled trials in patients with sepsis, these anticoagulants have not shown significantly reduced mortality. The aim of this assessment was to compare the heterogeneity in responses to treatment in the two trials according to different patient phenotypes. Results of the KyberSept and SCARLET trials reported in original and post-hoc publications were analyzed and directly compared for treatment effects in various patient subgroups. In both KyberSept and SCARLET, the septic coagulopathy phenotype that benefited most from endogenous anticoagulant supplementation showed markers of excessive activation of coagulation. Interaction between concomitant thromboprophylactic heparin and the endogenous anticoagulants abrogated the efficacy of both antithrombin and thrombomodulin. In both trials, higher disease severity was associated with better treatment outcome. In conclusion, in two landmark studies of endogenous anticoagulants in patients with sepsis, similar findings of beneficial effects in the coagulopathy phenotype and interactions with heparin comedication and disease severity support the potential roles that thrombomodulin and antithrombin might play in treating septic coagulopathy and disseminated intravascular coagulation. Further prospective validation is warranted. Future trial designs to definitively establish the therapeutic relevance of antithrombin and thrombomodulin in septic coagulopathy should focus on involvement of patients characterized by coagulopathy and disease severity as well as interactions between endogenous anticoagulants and exogenous heparin.

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Anticoagulation Therapy Using rh-Thrombomodulin and/or Antithrombin III Agent is Associated With Reduction in in-Hospital Mortality in Septic Disseminated Intravascular Coagulation: A Nationwide Registry Study

Cited by 17 publications

References 32 publications

Institutional Anticoagulation Protocol for Septic DIC is Associated with Differences in In-Hospital Mortality. J-SEPTIC DIC STUDY (A Nationwide Registry Study)

Institutional Anticoagulation Protocol for Septic DIC is Associated with Differences in In-Hospital Mortality. J-SEPTIC DIC STUDY (A Nationwide Registry Study)

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

Anticoagulant therapy for septic coagulopathy and disseminated intravascular coagulation: where do KyberSept and SCARLET leave us?

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