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Prediction of Early Death in Patients With Sepsis-Associated Coagulation Disorder Treated With Antithrombin Supplementation.

ABSTRACT: For success in clinical trials, eliminating inclusion of patients with irreversible recovery is important. The purpose of this study was to identify the patient population who do not survive for more than 3 days. A total of 449 patients with sepsis suspected of having disseminated intravascular coagulation (DIC) and treated with antithrombin were examined. The patient characteristics, baseline sequential organ failure assessment (SOFA) score, DIC score, and hemostatic markers were retrospectively analyzed in relation to early death (died within 3 days). At the end of day 3, a total of 419 patients had survived and 30 patients had died. A logistic regression analysis revealed a significant association between early death and the baseline prothrombin time-international normalized ratio PT-INR (P <.05) and the total SOFA score (P <.01). In contrast, neither the platelet count, fibrinogen/fibrin degradation products, and antithrombin activity nor the DIC score was associated with early death. Although the accuracy for predicting early death defined by either baseline PT-INR of ?1.57 or total SOFA score of more than 13 was not high enough, that of "high-risk of early death (PT-INR ? 1.57 and SOFA score ? 13)" was 83.5%. Furthermore, the negative predictive of this category was 96.0%. The baseline SOFA score and PT-INR were associated with early death among patients with sepsis-associated coagulation disorders. Patients who do not meet the "high-risk of early death" criteria were likely to survive for more than 3 days and therefore should be considered for future therapeutic clinical trials.

SUBMITTER: Iba T

PROVIDER: S-EPMC6714842 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Prediction of Early Death in Patients With Sepsis-Associated Coagulation Disorder Treated With Antithrombin Supplementation.

Iba Toshiaki T Arakawa Makoto M Ohchi Yoshifumi Y Arai Takao T Sato Koichi K Wada Hideo H Levy Jerrold H JH

Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis 20180909 9_suppl

For success in clinical trials, eliminating inclusion of patients with irreversible recovery is important. The purpose of this study was to identify the patient population who do not survive for more than 3 days. A total of 449 patients with sepsis suspected of having disseminated intravascular coagulation (DIC) and treated with antithrombin were examined. The patient characteristics, baseline sequential organ failure assessment (SOFA) score, DIC score, and hemostatic markers were retrospectivel ...[more]

PMID: 30198317

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Project description:BackgroundDisseminated intravascular coagulation (DIC) syndrome is a highly lethal condition characterized by the complication of multiple organ damage. Although the effects of combined antithrombin (AT) and recombinant thrombomodulin (rTM) on DIC syndrome have previously been examined, the results are inconsistent and inconclusive. Therefore, we conducted a systematic review on the combined administration of AT and rTM for the treatment of septic DIC to investigate the superiority of the combination therapy over either AT or rTM monotherapy using a random-effects analysis model.MethodWe searched electronic databases, including Medline, Cochrane Central Register of Controlled Trials, Scopus, and Igaku-Chuo Zasshi (ICHU-SHI) Japanese Central Review of Medicine Web from inception to January 2022. Studies assessing the efficacy of combined AT and rTM were included. The primary outcome was all-cause mortality, and the secondary outcome was occurrence of serious bleeding complications compared to monotherapy. We presented the pooled odds ratio (OR) or hazard ratio (HR) with 95% confidence intervals (CI) depending on reporting results in each primary study.ResultsWe analyzed seven enrolled clinical trials, all of which were observational studies. Combination therapy had a non-significant favorable association with lower 28-day mortality compared to monotherapy (HR 0.67 [0.43-1.05], OR 0.73 [0.45-1.18]). The I2 values were 60% and 72%, respectively, suggesting high heterogeneity. As a secondary outcome, bleeding complications were similar between the two groups (pooled OR 1.11 [0.55-2.23], I2 value 55%).ConclusionsAlthough the findings in this analysis could not confirm a statistically significant effect of AT and rTM combination therapy for septic DIC, it showed a promising effect in terms of improving mortality. The incidence of bleeding was low and clinically feasible. Further research is warranted to draw more conclusive results.Trial registrationThis study was registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN ID: 000049820).

Project description:Background: Atrial fibrillation (AF) and coagulation disorder, two common complications of sepsis, are associated with the mortality. However, the relationship between early coagulation disorder and AF in sepsis remains elusive. This study aimed to evaluate the interaction between AF and early coagulation disorder on mortality. Methods: In this retrospective study, all data were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. Septic patients with coagulation tests during the first 24 h after admission to intensive care units (ICUs) meeting study criteria were included in the analysis. Early coagulation disorder is defined by abnormalities in platelet count (PLT), international normalized ratio (INR) and activated partial thromboplastin time (APTT) within the first 24 h after admission, whose score was defined with reference to sepsis-induced coagulopathy (SIC) and coagulopathy. Patients meeting study criteria were divided into AF and non-AF groups. Results: In total, 7,528 septic patients were enrolled, including 1,243 (16.51%) with AF and 5,112 (67.91%) with early coagulation disorder. Compared with patients in the non-AF group, patients in the AF group had higher levels of INR and APTT (P < 0.001). Multivariable logistic regression analyses showed that stroke, early coagulation disorder, age, gender, congestive heart failure (CHF), chronic pulmonary disease, renal failure, and chronic liver disease were independent risk factors for AF. In addition, AF was related to in-hospital mortality and 90-day mortality. In the subgroup analysis stratified by the scores of early coagulation disorder, AF was associated with an increased risk of 90-day mortality when the scores of early coagulation disorder were 1 or 2 and 3 or 4. Conclusion: In sepsis, coagulation disorder within the first 24 h after admission to the ICUs is an independent risk factor for AF. The effect of AF on 90-day mortality varies with the severity of early coagulation disorder.

Project description:# Background Acute kidney injury (AKI) in sepsis patients increases patient mortality. Endothelial cells are important players in the pathophysiology of sepsis-associated AKI (SA-AKI), yet knowledge regarding their spatiotemporal involvement in coagulation disbalance and leukocyte recruitment is lacking. This study investigated the identity and kinetics of responses of different microvascular compartments in kidney cortex in response to SA-AKI. # Methods Laser microdissected arterioles, glomeruli, peritubular capillaries, and postcapillary venules from kidneys of mice subjected to cecal ligation and puncture (CLP) were analyzed using RNA sequencing. Differential expression and pathway enrichment analyses identified genes involved in coagulation and inflammation. A selection of these genes was evaluated by RT-qPCR in microvascular compartments of renal biopsies from patients with SA-AKI. The role of two identified genes in lipopolysaccharide-induced endothelial coagulation and inflammatory activation were determined in vitro in HUVEC using siRNA-based gene silencing. # Results CLP-sepsis in mice induced altered expression of approximately 400 genes in the renal microvasculature, with microvascular compartments exhibiting unique spatiotemporal responses. In mice, changes in gene expression related to coagulation and inflammation were most extensive in glomeruli at early and intermediate time points, with high induction of Plat, Serpine1, Thbd, Icam1, Stat3, and Ifitm3. In human SA-AKI, PROCR and STAT3 were induced in postcapillary venules, while SERPINE1 expression was diminished. IFITM3 was increased in arterioles and glomeruli. In vitro studies revealed that STAT3 and IFITM3 partly control endothelial coagulation and inflammatory activation. # Conclusion Renal microvascular compartments in mice and humans exhibited heterogeneous changes in coagulation- and inflammation-related gene expression in response to SA-AKI. Additional research should aim at understanding the functional consequences of the here described heterogeneous microvascular responses to establish the usefulness of identified genes as therapeutic targets in SA-AKI.

Dataset Information

Prediction of Early Death in Patients With Sepsis-Associated Coagulation Disorder Treated With Antithrombin Supplementation.

Publications

Prediction of Early Death in Patients With Sepsis-Associated Coagulation Disorder Treated With Antithrombin Supplementation.

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