IL (Interleukin)-6 Contributes to Deep Vein Thrombosis and Is Negatively Regulated by miR-338-5p

Zhang, Yunhong; Zhang, Zhen; Wei, Ran; Miao, Xiuming; Sun, Shenghua; Liang, Gang; Chu, Chu; Zhao, Lin; Zhu, Xiaoxiao; Guo, Qiang; Wang, Bin; Li, Xia

doi:10.1161/atvbaha.119.313137

Cited by 96 publications

(92 citation statements)

References 52 publications

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“…has demonstrated the increase risk of deep vein thrombosis with tumor derived IL-6 in the mouse model of ovarian cancer via the induction of hepatic thrombopoietin, promoting thrombus formation [12]. Moreover, IL-6 has been reported to contribute to deep vein thrombosis by dysregulation of miR-338-5p expression [16].…”

Section: Discussionmentioning

confidence: 99%

Tocilizumab and Thromboembolism in COVID-19: A Retrospective Hospital-based Cohort Analysis

Chan

Patel

Podel

et al. 2020

Preprint

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Background:Tocilizumab, an IL-6 receptor antagonist has been used in patients with Coronavirus Disease 2019 (COVID-19) as an anti-cytokine agent. IL-6 also plays a complex role in hemostasis and thrombosis. We observed a transient elevation of D-dimer in our patients who received Tocilizumab, which triggered the current study.Methods:A retrospective hospital-based cohort analysis of patients with confirmed COVID-19 who received Tocilizumab during the study period of 03/15/2020 to 05/20/2020. We retrieved demographic, clinical and laboratory data, we excluded patients who were receiving therapeutic anticoagulation therapy prior to Tocilizumab administration. Descriptive analysis was performed, the cause of death and trends of D-dimer and inflammatory markers were studied. Results: Out of the 436 confirmed COVID 19 patients admitted during the study period, 24 met the inclusion criteria. Their median age was 47.5 years old. They were 18 males and 6 females; 15 patients survived, and 9 expired. Of the group that survived, 12 received therapeutic anticoagulation. Of the 7 patients who did not receive therapeutic anticoagulation, 4 expired, 1 from sepsis and 3 probably from thromboembolic complications, compared to 5 deaths in the 17 patients who received therapeutic anticoagulation with 4 dying from sepsis, and one possibly from thromboembolic complications.Conclusions:The interplay between IL-6, IL-6 receptor antagonist and venous thromboembolism are complex. We observed a transient elevation of D-dimer in COVID-19 patients who received Tocilizumab, and a trend toward increased death secondary to thromboembolism. This observation is novel and highlights the potential thrombophilic side effects of Tocilizumab.

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Section: Discussionmentioning

confidence: 99%

Tocilizumab and Thromboembolism in COVID-19: A Retrospective Hospital-based Cohort Analysis

Chan

Patel

Podel

et al. 2020

Preprint

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“…Patients with complicated appendicitis were reported to have higher plasma IL-6 level than those with simple appendicitis [11]. Elevated IL-6 might have induced DVT [12] in those patients. Further study is needed to confirm this theory.…”

Section: Discussionmentioning

confidence: 99%

Incidence of postsurgical pulmonary embolism and deep venous thrombosis: a single-center retrospective observational study

Otsuka¹,

Izumi²,

Ota³

et al. 2020

JA Clin Rep

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Background: Cancer is a risk factor for perioperative deep venous thrombosis and pulmonary embolism (DVT/PE). However, there is a paucity of data on non-malignant digestive diseases. In this study, we aimed to investigate the incidence of DVT/PE among patients, following surgery for acute appendicitis and other digestive diseases.Methods: We retrospectively reviewed the records of patients who underwent surgical procedures involving the digestive system between April 2018 and March 2019 attended by anesthesiologists (n = 536).Results: DVT/PE developed in seven patients (7/77, 9.1%, 95% confidence interval [CI] 3.7-17.8%) after surgery for acute appendicitis, and in six patients (6/83, 7.2%, 95%CI 2.7-15.1%) after elective surgery for colorectal cancer. Among the acute appendicitis group, six patients (6/30 20.0%) with complicated appendicitis (gangrenous or perforated appendicitis), and one patient (1/47 2.1%) with simple appendicitis showed postoperative DVT/PE. Patients with complicated appendicitis had a higher risk of DVT/PE than those with simple appendicitis with an odds ratio of 11.5 (95%CI 1.3-101.1). Conclusions:Although patients with acute appendicitis lack three of the risk factors for DVT/PE (cancer, long operative time, and older age), their 95% CI for the incidence of DVT/PE was comparable to that of patients undergoing elective surgery for colorectal cancer. Therefore, caution must be exercised during the perioperative period for preventing DVT/PE.

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“…Sun et al (2020) [52] demonstrated that the expression level of miR-103a-3p was downregulated not only in patients with acute DVT (n = 81) versus healthy controls (n = 20) but also in a mouse model of DVT (IVC stenosis model). Zhang et al (2020) [53] demonstrated that the expression of miR-338-5p was substantially downregulated in peripheral blood mononuclear cells of DVT patients (n = 36) in comparison to healthy controls (n = 36). Consistent with the findings in DVT patients, the expression of miR-338-5p was significantly lower in a mouse model of DVT (IVC stenosis model) versus control mice [53].…”

Section: Epidemiological Studies: Mirnas and Venous Thromboembolismmentioning

confidence: 99%

“…Zhang et al (2020) [53] demonstrated that the expression of miR-338-5p was substantially downregulated in peripheral blood mononuclear cells of DVT patients (n = 36) in comparison to healthy controls (n = 36). Consistent with the findings in DVT patients, the expression of miR-338-5p was significantly lower in a mouse model of DVT (IVC stenosis model) versus control mice [53].…”

Section: Epidemiological Studies: Mirnas and Venous Thromboembolismmentioning

confidence: 99%

“…Such finding reinforces the potential role of miR-103a-3p in the pathogenesis of VTE, since this miRNA has also been found to be downregulated in VTE patients in three different studies [52,54,55] as previously described (Table 2). Zhang et al (2020) [53] reported that intravenous administration of miR-338-5p mimics resulted in decreased interleukin-6 expression and venous thrombus formation. In vitro assays confirmed that miR-338-5p regulated interleukin-6 expression.…”

Section: Modulation Of Mirna Activity In Animal Models Of Venous Thromentioning

confidence: 99%

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Role of microRNAs in Venous Thromboembolism

Morelli

Brækkan

Hansen

2020

IJMS

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MicroRNAs (miRNAs) are non-coding RNAs that execute their function by targeted downregulation of gene expressions. There is growing evidence from epidemiological studies and animal models suggesting that the expression level of miRNAs is dysregulated in venous thromboembolism (VTE). In this review, we summarize the current knowledge on the role of miRNAs as biomarkers for VTE and provide general insight into research exploring the modulation of miRNA activity in animal models of venous thrombosis. Up to now, published studies have yielded inconsistent results on the role of miRNAs as biomarkers for VTE with most of the reports focused on diagnostic research. The limited statistical power of the individual studies, due to the small sample sizes, may substantially contribute to the poor reproducibility among studies. In animal models, over-expression or inhibition of some miRNAs appear to influence venous thrombus formation and resolution. However, there is an important gap in knowledge on the potential role of miRNAs as therapeutic targets in VTE. Future research involving large cohorts should be designed to clarify the clinical usefulness of miRNAs as biomarkers for VTE, and animal model studies should be pursued to unravel the role of miRNAs in the pathogenesis of VTE and their potential as therapeutic targets.

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IL (Interleukin)-6 Contributes to Deep Vein Thrombosis and Is Negatively Regulated by miR-338-5p

Cited by 96 publications

References 52 publications

Tocilizumab and Thromboembolism in COVID-19: A Retrospective Hospital-based Cohort Analysis

Tocilizumab and Thromboembolism in COVID-19: A Retrospective Hospital-based Cohort Analysis

Incidence of postsurgical pulmonary embolism and deep venous thrombosis: a single-center retrospective observational study

Role of microRNAs in Venous Thromboembolism

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