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Effect of High-dose Antithrombin Supplementation in Patients with Septic Shock and Disseminated Intravascular Coagulation.

ABSTRACT: The efficacy of antithrombin (AT) administration in patients with septic shock and disseminated intravascular coagulation (DIC) was uncertain. This study aimed to investigate whether high-dose AT administration improves outcomes in patients with septic shock and DIC. This observational, prospective cohort study included consecutive adult septic shock patients with DIC who showed AT activity <70% between March 2016 and August 2018. The 28 day mortality of the patients treated with AT and without AT was evaluated by propensity score matching and inverse probability of treatment weighting. Among 142 patients with septic shock and DIC, 45 patients (31.7%) received AT supplementation and 97 did not. The 28 day mortality rate was lower in the AT group, but no statistically significant difference persisted after matching. Multivariable analysis showed that AT supplementation was independently associated with 28 day mortality (odds ratio [OR], 0.342; 95% CI [confidence interval], 0.133-0.876; P?=?0.025); however, no such association was observed after matching (OR, 0.480; 95% CI, 0.177-1.301; P?=?0.149). High-dose AT administration in septic shock patients with DIC showed the improvement in survival, but the improvement was not observed after matching. Further larger studies are needed to conclusively confirm these findings.

SUBMITTER: Kim YJ

PROVIDER: S-EPMC6851090 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Effect of High-dose Antithrombin Supplementation in Patients with Septic Shock and Disseminated Intravascular Coagulation.

Kim Youn-Jung YJ Ko Byuk Sung BS Park Seo Young SY Oh Dong Kyu DK Hong Sang-Bum SB Jang Seongsoo S Kim Won Young WY

Scientific reports 20191112 1

The efficacy of antithrombin (AT) administration in patients with septic shock and disseminated intravascular coagulation (DIC) was uncertain. This study aimed to investigate whether high-dose AT administration improves outcomes in patients with septic shock and DIC. This observational, prospective cohort study included consecutive adult septic shock patients with DIC who showed AT activity <70% between March 2016 and August 2018. The 28 day mortality of the patients treated with AT and without ...[more]

PMID: 31719571

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Project description:BackgroundThere is no gold standard to diagnose septic shock-induced disseminated intravascular coagulation (DIC). The objective of our multicenter prospective study was to assess the performances of the different major scoring systems in terms of mortality prediction and DIC diagnosis. The JAAM-DIC 2016 score, the ISTH overt-DIC 2001 score, the associations of sepsis-induced coagulopathy (SIC) score with JAAM-DIC 2016 or ISTH overt-DIC scores were tested in patients within 12 h of their admission in ICU for septic shock (day 1) and at day 2.Results582 patients were enrolled in the study. 182/567 (32.1%) were diagnosed with DIC according to ISTH overt-DIC score, and 193/561 (34.4%) according to JAAM-DIC score; 486/577 patients (84.2%) were diagnosed with a coagulopathy according to SIC score. A moderate concordance was observed between ISTH overt-DIC and JAAM-DIC [κ = 0.67 (0.60, 0.73), p < 0.001]. The delay of positivity of the scores for early DIC patients was not different between JAAM-DIC and ISTH overt-DIC scores. Although it was positive earlier, SIC score had worse diagnosis specificity, as 84.2% of the patients with septic shock were diagnosed with "coagulopathy". The specificity of SIC score alone to predict mortality was very low [0.18 (0.15; 0.22)], compared to the ones of JAAM-DIC score [0.71 (0.67; 0.75)], and of ISTH overt-DIC score [0.76 (0.72; 0.80)], p < 0.001. The sensitivity of SIC score to predict mortality was 0.95 [0.89; 0.98], and the ones of JAAM-DIC score and ISTH overt-DIC score were 0.61 [0.50; 0.70] and 0.68 [0.58; 0.77], respectively. There was no benefit in sensitivity and specificity in combining SIC score to JAAM-DIC score or to ISTH overt-DIC score, compared to JAAM-DIC score or ISTH overt-DIC score alone.ConclusionsOur data suggest that the added value of SIC score alone or combined with other scores is limited, and that both JAAM-DIC score and ISTH overt-DIC score can be used in septic shock patients. Trial registration clinicaltrial; Trial registration number: NCT02391792; Date of registration: 18/03/2015; URL of trial registry record: https://clinicaltrials.gov/ct2/show/NCT02391792?term=meziani&draw=4&rank=1.

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.

Project description:Objectives: Patients with disseminated intravascular coagulation (DIC) due to sepsis often develop cerebral infarction; but the frequency, mechanism of onset and prognosis have not been fully elucidated. We reported courses and characteristics of septic DIC cases hospitalized in our hospital in the present study. Methods: Patients with septic DIC who underwent brain imaging were selected. Vital signs, disorders of consciousness and blood test results at the time of onset were compared between cases that developed cerebral infarction (cerebral infarction group) and those that did not (non-infarction group).In cases of cerebral infarction, the site and the size of the infarct lesion were also described. Results: In 27 septic DIC patients who underwent brain imaging, eight patients had cerebral infarction. Although the percentage of patients who survived in the cerebral infarction group (2/8, 25%) was lower than that in the non-infarction group (7/17, 37%), , no significant difference was observed as both group showed poor prognoses. Those two patients who survived in the cerebral infarction group had severe consciousness disturbance and poor functional prognosis. Although the body temperature was significantly lower and the blood pressure was higher in the cerebral infarction group, no significant difference was found in general blood tests, so we thought it would be necessary to look for other markers that could be indicators for the risk of cerebral infarction. In the cerebral infarction group, two cases had a single lesion, and six cases had multiple lesions. Of the latter, two cases had massive lesions with a diameter of 1.5 cm or greater, four cases had only small lesions with a diameter of less than 1.5 cm, and two cases had a mixture of both. Most of the patients had lesions in the vertebrobasilar artery, which suggested that the pathogenesis involves not only embolism due to microthrombi, but also vasculitis and intravascular inflammation. Conclusions: Cerebral infarction was observed highly frequently; eight out of 27 cases (29.6%) when brain imaging was undergone in septic DIC patients. The prognosis of patients with cerebral infarction was poor, but no difference from the non-infarction group was observed. In addition to embolism, the presence of inflammation is considered to be important for the onset. In order to predict the prognosis and determine a suitable treatment, it would be recommended to undergo brain imaging when patients with septic DIC have consciousness disturbance or elevated blood pressure, and do not have fever.

Dataset Information

Effect of High-dose Antithrombin Supplementation in Patients with Septic Shock and Disseminated Intravascular Coagulation.

Publications

Effect of High-dose Antithrombin Supplementation in Patients with Septic Shock and Disseminated Intravascular Coagulation.

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