Antithrombin: anti-inflammatory properties and clinical applications

Levy, Jerrold H.; Sniecinski, Roman M.; Welsby, Ian J.; Levi, Marcel

doi:10.1160/th15-08-0687

Cited by 142 publications

(72 citation statements)

References 120 publications

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“…Second, differences between groups are likely to be statistically significant if the control event rate is high. Third, anticoagulants such as antithrombin and rhTM have specific anti-inflammatory activities unrelated to anticoagulant activity [ 30 – 32 ], and these anti-inflammatory effects might be clinically evident only in the severely ill patients.…”

Section: Discussionmentioning

confidence: 99%

Benefit profile of anticoagulant therapy in sepsis: a nationwide multicentre registry in Japan

et al. 2016

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BackgroundLittle evidence supports anticoagulant therapy as effective adjuvant therapy to reduce mortality overall in sepsis. However, several studies suggest that anticoagulant therapy may reduce mortality in specific patients. This study aimed to identify a subset of patients with high benefit profiles for anticoagulant therapy against sepsis.MethodsThis post hoc subgroup analysis of a nationwide multicentre retrospective registry was conducted in 42 intensive care units in Japan. Consecutive adult patients with sepsis were included. Treatment effects of anticoagulants, e.g. antithrombin, recombinant thrombomodulin, heparin, and protease inhibitors, were evaluated by stratifying patients according to disseminated intravascular coagulation (DIC) and Sequential Organ Failure Assessment (SOFA) score. Intervention effects of anticoagulant therapy on in-hospital mortality and bleeding complications were analysed using Cox regression analysis stratified by propensity scores.ResultsParticipants comprised 2663 consecutive patients with sepsis; 1247 patients received anticoagulants and 1416 received none. After adjustment for imbalances, anticoagulant administration was significantly associated with reduced mortality only in subsets of patients diagnosed with DIC, whereas similar mortality rates were observed in non-DIC subsets with anticoagulant therapy. Favourable associations between anticoagulant therapy and mortality were observed only in the high-risk subset (SOFA score 13–17; adjusted hazard ratio 0.601; 95 % confidence interval 0.451, 0.800) but not in the subsets of patients with sepsis with low to moderate risk. Although the differences were not statistically significant, there was a consistent tendency towards an increase in bleeding-related transfusions in all SOFA score subsets.ConclusionsThe analysis of this large database indicates anticoagulant therapy may be associated with a survival benefit in patients with sepsis-induced coagulopathy and/or very severe disease.Trial registrationUniversity Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR ID: UMIN000012543). Registered on 10 December 2013.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1415-1) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Benefit profile of anticoagulant therapy in sepsis: a nationwide multicentre registry in Japan

et al. 2016

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“…Some anti-inflammatory actions of antithrombin are mediated by its anticoagulation action, whereas others are not [5,6]. …”

Section: The Mechanism Of Atiii Actionmentioning

confidence: 99%

“…antithrombin inhibits factor Xa-induced production of interleukin (IL)-6 and IL-8, as well as other molecules involved in monocyte recruitment and adhesion to endothelial cells [6]. …”

Section: The Mechanism Of Atiii Actionmentioning

confidence: 99%

SerpinC1/Antithrombin III in kidney-related diseases

Wang

Liang

2017

Clinical Science

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The gene SerpinC1 encodes a serine protease inhibitor named antithrombin III (ATIII). This protease demonstrates both anticoagulant and anti-inflammatory action. ATIII is the most important coagulation factor inhibitor, and even minor changes in ATIII can significantly alter the risk of thromboembolism. ATIII can also suppress inflammation via a coagulation-dependent or -independent effect. Moreover, apart from ATIII deficiency, ATIII and its gene SerpinC1 may also be related to many diseases (e.g. hypertension, kidney diseases). The present review summarizes how ATIII affects the progress of kidney disease and its mechanism. Further studies are required to investigate how ATIII affects renal function and the treatment.

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“…In the present study, early heparin + antithrombin treatment significantly inhibited inflammation and suppressed the activities of caspase-3 and caspase-9 through the inhibition of NF-κB/p65 in the rabbit model of severe burns complicated by inhalation injury. Levy et al ( 16 ) also showed that antithrombin possesses noteworthy anti-inflammatory properties.…”

Section: Discussionmentioning

confidence: 99%

Early anticoagulation therapy for severe burns complicated by inhalation injury in a rabbit model

Guo

Xiong

et al. 2017

Molecular Medicine Reports

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The aim of the present study was to determine the effects of early anticoagulation treatment on severe burns complicated by inhalation injury in a rabbit model. Under anesthetization, an electrical burns instrument (100°C) was used to scald the backs of rabbits for 15 sec, which established a 30% III severe burns model. Treatment of the rabbits with early anticoagulation effectively improved the severe burns complicated by inhalation injury-induced lung injury, reduced PaO2, PaCO2 and SPO2 levels, suppressed the expression of tumor necrosis factor-α, interleukin (IL)-1β and IL-6, and increased the activity of IL-10. In addition, it was found that early anticoagulation treatment effectively suppressed the activities of caspase-3 and caspase-9, upregulated the protein expression of vascular endothelial growth factor (VEGF) and decreased the protein expression of protease-activated receptor 1 (PAR1) in the severe burns model. It was concluded that early anticoagulation treatment affected the severe burns complicated by inhalation injury in a rabbit model through the upregulation of VEGF and downregulation of PAR1 signaling pathways. Thus, early anticoagulation is a potential therapeutic option for severe burns complicated by inhalation injury.

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Antithrombin: anti-inflammatory properties and clinical applications

Cited by 142 publications

References 120 publications

Benefit profile of anticoagulant therapy in sepsis: a nationwide multicentre registry in Japan

Benefit profile of anticoagulant therapy in sepsis: a nationwide multicentre registry in Japan

SerpinC1/Antithrombin III in kidney-related diseases

Early anticoagulation therapy for severe burns complicated by inhalation injury in a rabbit model

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