Observational study to compare antithrombin and thrombomodulin for disseminated intravascular coagulation

Murata, Atsuhiko; Okamoto, Kohji; Mayumi, Toshihiko; Muramatsu, Keiji; Matsuda, Shinya

doi:10.1007/s11096-014-0052-5

Cited by 14 publications

(14 citation statements)

References 32 publications

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“…Despite the differences in DIC aetiology, the findings of our study corroborate their conclusions. However, it should be noted that the length of hospital stay in our study subjects was approximately 20 days longer than that of the subjects in Murata et al 17 . This disparity could be due to our focus on more severe patients who required mechanical ventilation for respiratory dysfunction.…”

Section: Discussioncontrasting

confidence: 61%

“…A retrospective study used propensity-score matching and instrumental variable analyses to examine mechanically ventilated patients with sepsis and DIC after intestinal perforation, and found no association between TM administration and 28-day mortality 21 . Similarly, other studies using DPC databases have also reported no associations between anticoagulant therapies and mortality in septic patients with DIC 17,21 . TM administration in mechanically ventilated patients with acute respiratory distress syndrome and DIC has also been found to improve oxygenation 22 .…”

Section: Discussionmentioning

confidence: 81%

“…The study showed that AT + TM combination therapy was not significantly associated with reduced in-hospital mortality when compared with AT monotherapy. In another analysis of Japanese administrative data, Murata et al similarly found no significant differences in in-hospital mortality between AT and TM in patients with infection-associated DIC 17 . Despite the differences in DIC aetiology, the findings of our study corroborate their conclusions.…”

Section: Discussionmentioning

confidence: 93%

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Effectiveness of combined antithrombin and thrombomodulin therapy on in-hospital mortality in mechanically ventilated septic patients with disseminated intravascular coagulation

Umegaki

Kunisawa

Nishimoto

et al. 2020

Sci Rep

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Septic patients can develop disseminated intravascular coagulation (DIC), which is characterized by systemic blood coagulation and an increased risk of life-threatening haemorrhage. Although antithrombin (AT) and thrombomodulin (TM) combination anticoagulant therapy is frequently used to treat septic patients with DIC in Japan, its effectiveness in improving patient outcomes remains unclear. In this large-scale multicentre retrospective study of adult septic patients with DIC treated at Japanese hospitals between February 2010 and March 2016, we compared in-hospital mortality between AT monotherapy and AT + TM combination therapy. We performed logistic regression analysis with in-hospital mortality as the dependent variable and anticoagulant therapy as the main independent variable of interest. Covariates included patient demographics, disease severity, and body surface area. The AT group and AT + TM group comprised 1,017 patients from 352 hospitals and 1,205 patients from 349 hospitals, respectively. AT + TM combination therapy was not significantly associated with lower mortality when compared with AT monotherapy (odds ratio: 0.97, 95% confidence interval: 0.78-1.21; P = 0.81). AT + TM combination therapy was also not superior to AT monotherapy in reducing mechanical ventilation or hospitalization durations. Despite its widespread use for treating sepsis with DIC, AT + TM combination therapy is not more effective in improving prognoses than the simpler AT monotherapy. Sepsis can lead to disseminated intravascular coagulation (DIC), which is a serious condition characterized by widespread coagulation throughout a patient's bloodstream 1,2. The rapid depletion of blood coagulation factors in these patients increases the risk of potentially fatal haemorrhage. In Japan, this condition was responsible for 10,318 deaths per 100,000 population in 2018, which was comparable to the mortality rates of oesophageal tumours and malignant lymphomas 3. Antithrombin (AT) and thrombomodulin (TM) are frequently administered together as anticoagulant therapy to treat septic patients with DIC in Japan. In a meta-analysis of sepsis-induced DIC, Yatabe et al. reported that AT use is a key factor in DIC resolution 4. A phase III trial conducted between 2000 and 2005 found that TM was not significantly associated with improvements in 28-day mortality when compared with heparin, but that its use significantly improved DIC 5. Similarly, the multinational, multicentre SCARLET randomized clinical trial reported that TM use in patients with sepsis-associated coagulopathy was not significantly associated with reduced mortality 6. In Japan, a multicentre post-marketing survey conducted between 2014 and 2016 showed that approximately half of 510 sepsis-associated DIC patients were treated with AT + TM combination therapy despite the lack of evidence to support its use 7. However, little is known about the effectiveness of AT + TM combination

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Section: Discussioncontrasting

confidence: 61%

Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 93%

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Effectiveness of combined antithrombin and thrombomodulin therapy on in-hospital mortality in mechanically ventilated septic patients with disseminated intravascular coagulation

Umegaki

Kunisawa

Nishimoto

et al. 2020

Sci Rep

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“…Similarly, it was shown that factor VII deficiency is frequent in patients with infections, neoplasia, trauma, nephrotic syndrome, left heart failure, penicillin intake and clearly in patients under vitamin K dependent anticoagulation[34, 35]. However, ATIII should only be altered due to mutations[36], consumption[37] or hepatocellular dysfunction[38, 39]. …”

Section: Discussionmentioning

confidence: 99%

Early prediction of postoperative liver dysfunction and clinical outcome using antithrombin III-activity

et al. 2017

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Background and aimsAntithrombin III (ATIII) has been reported to be associated with liver pathologies and was shown to predict outcome in patients undergoing liver resection for hepatocellular carcinoma. We now aimed to assess whether perioperative ATIII-activity could predict postoperative outcome in patients without underlying liver disease, as well as in a routine clinical setting of patients undergoing hepatic resection.MethodsATIII-activity was evaluated preoperatively and on the first (POD1) and fifth day after liver resection in a retrospective evaluation cohort of 228 colorectal cancer patients with liver metastasis (mCRC). We further aimed to prospectively validate our results in a set of 177 consecutive patients undergoing hepatic resection.ResultsPatients developing postoperative liver dysfunction (LD) had a more pronounced postoperative decrease in ATIII-activity (P<0.001). ATIII-activity on POD1 significantly predicted postoperative LD (P<0.001, AUC = 84.4%) and remained independent upon multivariable analysis. A cut-off value of 61.5% ATIII-activity was determined using ROC analysis. This cut-off was vital to identify high-risk patients for postoperative LD, morbidity, severe morbidity and mortality (P<0.001, respectively) with a highly accurate negative predictive value of 97%, which could be confirmed for LD (P<0.001) and mortality (P = 0.014) in our independent validation cohort. Further, mCRC patients below our cut-off suffered from a significantly decreased overall survival (OS) at 1 and 3 years after surgery (P = 0.011, P = 0.025).ConclusionsThe routine laboratory parameter ATIII-activity on POD1 independently predicted postoperative LD and was associated with clinical outcome. Patients with a postoperative ATIII-activity <61.5% might benefit from close monitoring and timely initiation of supportive therapy.Trial registrationClinicalTrials.gov NCT01700231

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“…The data are coded using the International Classification of Diseases, tenth revision (ICD-10). Neonatologists routinely enter diagnoses in the patient medical records, and the use of the DPC data in clinical reports involving diverse medical specialties has been increasing [7][8][9][10][11][12], but there have been no previous studies on neonatal DIC using the DPC database in Japan. The aim of this retrospective study was to estimate the incidence and prognosis of neonatal DIC in Japan by analyzing the data available in the national administrative DPC database.…”

Section: Introductionmentioning

confidence: 99%

Incidence and In-Hospital Mortality of Neonatal Disseminated Intravascular Coagulation in Japan: An Observational Study of a Nationwide Hospital Claims Database

Araki

Tomioka

Otani

et al. 2019

J UOEH

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This study aimed to estimate the incidence and prognosis of neonatal disseminated intravascular coagulation (DIC) in Japan by analyzing data retrieved from a national administrative database. Clinically, the prognosis of DIC in neonates is poor, but there is little epidemiological data in Japan. This retrospective observational study identified patients diagnosed with neonatal DIC and who were registered in the Japanese diagnosis procedure combination (DPC) database between April 1, 2014 and March 31, 2016. The patients, who were diagnosed with neonatal DIC, included those with ICD-10 code D65 or P60 in primary and secondary diagnosis, with comorbid conditions existing at admission, and with complications occurring after admission. Of 78,073 neonates admitted to 1,474 neonatal intensive care units, 1,864 (2.4%) were diagnosed with DIC. There was no difference between sexes in incidence of DIC; the incidence of DIC was higher in extremely low birth weight infants (9.8%), and significantly higher than that in normal birth weight infants. The overall mean length of hospital stay was longer in neonates with DIC (69.5 days) than in those without DIC (32.6 days, P < 0.001). The number of deaths was 1,156 (1.5%). In-hospital mortality was significantly higher in neonates with DIC (14.1%) than in those without DIC (1.2%, P < 0.001), especially in premature babies. This nationwide study was the first report to investigate the incidence and in-hospital mortality of neonatal DIC in Japan. Neonatal DIC has a significant impact on prognosis, and its influence is greater in premature than in term infants.

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Observational study to compare antithrombin and thrombomodulin for disseminated intravascular coagulation

Abstract: This study demonstrated no significant difference in in-hospital mortality between AT-III and rhs-TM. However, use of rhs-TM was significantly associated with decreased LOS and medical costs during hospitalization in patients with DIC associated with infectious diseases.

Cited by 14 publications

References 32 publications

Effectiveness of combined antithrombin and thrombomodulin therapy on in-hospital mortality in mechanically ventilated septic patients with disseminated intravascular coagulation

Effectiveness of combined antithrombin and thrombomodulin therapy on in-hospital mortality in mechanically ventilated septic patients with disseminated intravascular coagulation

Early prediction of postoperative liver dysfunction and clinical outcome using antithrombin III-activity

Incidence and In-Hospital Mortality of Neonatal Disseminated Intravascular Coagulation in Japan: An Observational Study of a Nationwide Hospital Claims Database

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