Antithrombin III for critically ill patients: a systematic review with meta-analysis and trial sequential analysis

Allingstrup, Mikkel; Wetterslev, Jørn; Ravn, Frederikke B.; Møller, Ann Merete; Afshari, Arash

doi:10.1007/s00134-016-4225-7

Cited by 82 publications

(88 citation statements)

References 47 publications

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“…In the past, similar rationale has driven research on activated protein C and antithrombin III as adjunctive treatments for sepsis. However, compilation of the available evidence does not support their efficacy, and both are associated with bleeding complications . Interestingly, ADAMTS13 supplementation has no or minimal effect on bleeding .…”

Section: Discussionmentioning

confidence: 99%

Von Willebrand factor and ADAMTS13 impact on the outcome of Staphylococcus aureus sepsis

Peetermans

Meyers

Liesenborghs

et al. 2020

Journal of Thrombosis and Haemostasis

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Background Previous clinical evidence correlates levels of von Willebrand factor (VWF) and its cleaving protease ADAMTS13 with outcome in septic patients. No previous studies addressed if VWF and ADAMTS13 affected the outcome of Staphylococcus aureus sepsis. Objectives We studied the role of VWF and ADAMTS13 in S. aureus sepsis both in patients and in mice. Methods VWF levels and ADAMTS13 activity levels were measured in plasma samples from 89 S. aureus bacteremia patients by chemiluminescent assays and were correlated with clinical sepsis outcome parameters. In wild‐type mice and mice deficient in VWF and ADAMTS13, we investigated the outcome of S. aureus sepsis and quantified bacterial clearance and organ microthrombi. Results In patients with S. aureus bloodstream infections, high VWF levels and low ADAMTS13 activity levels correlated with disease severity and with parameters of inflammation and disseminated intravascular coagulation. In septic mice, VWF deficiency attenuated mortality, whereas ADAMTS13 deficiency increased mortality. Bacterial clearance was enhanced in VWF‐deficient mice. The differences in mortality for the studied genotypes were associated with differential loads of organ microthrombi in both liver and kidneys. Conclusions In conclusion, this study reports the consistent relation of VWF, ADAMTS13 and their ratio to disease severity in patients and mice with S. aureus sepsis. Targeting VWF multimers and/or the relative ADAMTS13 deficiency that occurs in sepsis should be explored as a potential new therapeutic target in S. aureus endovascular infections.

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Section: Discussionmentioning

confidence: 99%

Von Willebrand factor and ADAMTS13 impact on the outcome of Staphylococcus aureus sepsis

Peetermans

Meyers

Liesenborghs

et al. 2020

Journal of Thrombosis and Haemostasis

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“…It was reported that ATⅢ supplementation exhibited beneficial effects on organ function [48], protected against development of venous thromboembolism [49], and decreased mortality [49, 50] in patients with sepsis. Nevertheless, several meta-analyses have shown no significant beneficial effect of ATⅢ substitution on mortality in critically ill patients, whereas ATⅢ increased the risk of bleeding, especially in patients receiving concomitant heparin [51-53]. …”

Section: Discussionmentioning

confidence: 99%

“…Secondly, we should be discreet about concomitant use of heparin. Heparin can not only overwhelmingly accelerate the anticoagulant effect of ATⅢ, but competitively prevent ATⅢ from interacting with the endothelial cellular receptors, eventually reducing ATⅢ’s anti-inflammatory properties, weakening vascular protection, and increasing the risk of bleeding [51]. Thirdly, randomized controlled trials are required to verify the clinical value of ATⅢ supplementation before contrast medium administration in protecting patients with low ATⅢ activities from developing CIN.…”

Section: Discussionmentioning

confidence: 99%

Antithrombin Ⅲ is a Novel Predictor for Contrast Induced Nephropathy After Coronary Angiography

Kong

Yin

et al. 2018

Kidney Blood Press Res

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Background/Aims: Antithrombin Ⅲ (AT Ⅲ) is an important endogenous anticoagulant and has strong anti-inflammatory properties. Low ATⅢ activity is considered to be a predictor of poor outcomes in several conditions, including acute kidney injury after cardiac surgery. However, the association between the ATⅢ level and the occurrence of contrast induced nephropathy (CIN) has not been elucidated. In this study, our aim was to identify the potential predictive value of ATⅢ for CIN. Methods: We enrolled a total of 460 patients who underwent coronary angiography (CAG) from January 2015 to December 2016 in coronary care units (CCU). ATⅢ activity in plasma collected before CAG was measured and <75% was considered low activity according to reference values. A cross-sectional study on CIN after CAG was conducted and the risk factors were analyzed. CIN was diagnosed according to the KDIGO guideline. Results: Of these 460 patients undergoing CAG, 125 (27.17%) progressed to CIN. The incidence of CIN was significantly higher in patients with low ATⅢ activity compared to patients with normal ATⅢ activity (Pearson’s chi-squared test P=0.002). As ATⅢ activity declined, the prevalence of CIN progressively increased, with the highest value (58.8%) in patients with an ATⅢ activity <60%. Moreover, the ATⅢ activity was significantly lower in CIN patients than in non-CIN patients (84.43±16.3% vs. 92.14±13.94%, P<0.001). After multivariable analysis, ATⅢ activity <75% remained a significant independent predictor of CIN (OR 2.207,95%CI [1.29-3.777]; P=0.004) as well as baseline serum creatinine (OR 1.009,95%CI [1.001-1.016]; P=0.026). Conclusions: Patients with low ATⅢ activity had a higher risk of developing CIN after CAG. The initial ATⅢ activity may be a novel independent predictor for CIN.

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“…The study was stopped early because of safety issues: the composite primary outcome of prolonged ICU stay and 30-day mortality was 79 vs. 67%, in-ICU mortality was 79 vs. 39%, and 30-day mortality was 68 vs 39% in the protein C zymogen group vs the placebo group. Concordantly, a systematic review with meta-analysis and trial sequential analysis assessed use of antithrombin III (AT III) in critically ill patients (30 RCTs, 3933 patients), and found no benefit of AT III in critically ill patients in general or in different subgroups of critically ill patients [16]. Importantly, use of AT III significantly increased bleeding events.…”

Section: Bleeding In the Intensive Care Unitmentioning

confidence: 99%

ICM focus on thrombosis and bleeding

2017

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Antithrombin III for critically ill patients: a systematic review with meta-analysis and trial sequential analysis

Cited by 82 publications

References 47 publications

Von Willebrand factor and ADAMTS13 impact on the outcome of Staphylococcus aureus sepsis

Von Willebrand factor and ADAMTS13 impact on the outcome of Staphylococcus aureus sepsis

Antithrombin Ⅲ is a Novel Predictor for Contrast Induced Nephropathy After Coronary Angiography

ICM focus on thrombosis and bleeding

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