The Factor VIII Acute Phase Response Requires the Participation of NFκB and C/EBP

Notley, Colleen; Tinlin, Shawn; Sawyer, Lisa; Begbie, Megan E.; Lillicrap, David

doi:10.1055/s-0037-1613999

Cited by 71 publications

(16 citation statements)

References 36 publications

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“…Our results demonstrate that the patients receiving colchicine had a more significant percentage decrease in D -dimer levels compared to the control group. Direct endothelial injury caused by inflammatory cytokines has been shown to cause a state of hypercoagulability, which can lead to an increase in D -dimer levels [ 27 ]. Colchicine's anti-inflammatory properties may be responsible for the lower rise of the D -dimer levels in patients who received colchicine, which could function as an adjunctive treatment to anticoagulants.…”

Section: Discussionmentioning

confidence: 99%

A Case Control Study to Evaluate the Impact of Colchicine on Patients Admitted to the Hospital with Moderate to Severe COVID-19 Infection

Sandhu

Tieng

Chilimuri

et al. 2020

Canadian Journal of Infectious Diseases and Medical Microbiolog

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Background. Colchicine has been used in conditions such as periodic febrile illness, acute pericarditis, and gouty arthritis, all having a common hyperinflammatory response as seen in moderate to severe forms of coronavirus disease 2019 (COVID-19). This project was carried out during the rapid surge of cases in New York City, and the goal was to assess the efficacy of colchicine in treating patients with COVID-19. Methods. Patients admitted to two distinct pulmonary oriented floors of the BronxCare Hospital Center were compared. Patients on one floor were given colchicine in addition to standard of care, while control patients from another floor received only standard of care. Patients who had at least two separate timepoint measurements for at least two out of four serum inflammatory markers (C-reactive protein (CRP), D-dimer, ferritin, or lactate dehydrogenase (LDH)) were selected for the final comprehensive analysis. Results. An initial analysis performed on all patients, irrespective of the availability of two timepoint inflammatory markers, revealed a lower mortality (49.1% versus 72.9%, P = 0.002 ), a lower percentage of intubations (52.8% versus 73.6%, P = 0.006 ), and a higher discharge rate (50.9% versus 27.1%, P = 0.002 ), in the patients who received colchicine. Patients in the final comprehensive analysis groups (34 in the colchicine group and 78 in the control group) had a similar prevalence of comorbid medical conditions, except for renal failure, which was higher in the control group (65.3% versus 35.2%, P = 0.015 ). HTN (71.8% versus 52.9%, P = 0.053 ) and DM (51.3% versus 32.4%, P = 0.064 ) were also more prevalent in the control group, although the difference was not statistically significant. Patients who received colchicine had a lower mortality than the control group (47.1% versus 80.8%, P = 0.0003 ), lower rate of intubations (47.1% versus 87.2%, P < 0.0001 ), and a higher discharge rate (52.9% versus 19.2%, P = 0.0003 ). Patients in the colchicine group also showed a more significant decrease in inflammatory markers for D-dimer ( P = 0.037 ), CRP ( P = 0.014 ), and ferritin ( P = 0.012 ). Conclusions. Our study demonstrates that colchicine improved outcomes in patients with COVID-19 receiving standard of care therapy. Future randomized, placebo-controlled clinical trials to assess the potential benefit of colchicine in COVID-19 are warranted.

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Section: Discussionmentioning

confidence: 99%

A Case Control Study to Evaluate the Impact of Colchicine on Patients Admitted to the Hospital with Moderate to Severe COVID-19 Infection

Sandhu

Tieng

Chilimuri

et al. 2020

Canadian Journal of Infectious Diseases and Medical Microbiolog

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“…Furthermore, a variety of coagulation factors and regulators are induced by NF-κB, including tissue factor [F3, (121)], factor VIII (122), urokinase-type plasminogen activator (uPA) (123), and Plasminogen activator inhibitor-1 (PAI-1) (124). Thus, NF-κB contributes to coagulatory events not only via cellular activation processes, but also by transcriptional induction of proteins of the plasmatic coagulation cascade.…”

Section: Nf-κb Signaling Pathwaysmentioning

confidence: 99%

Cell Type-Specific Roles of NF-κB Linking Inflammation and Thrombosis

et al. 2019

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The transcription factor NF-κB is a central mediator of inflammation with multiple links to thrombotic processes. In this review, we focus on the role of NF-κB signaling in cell types within the vasculature and the circulation that are involved in thrombo-inflammatory processes. All these cells express NF-κB, which mediates important functions in cellular interactions, cell survival and differentiation, as well as expression of cytokines, chemokines, and coagulation factors. Even platelets, as anucleated cells, contain NF-κB family members and their corresponding signaling molecules, which are involved in platelet activation, as well as secondary feedback circuits. The response of endothelial cells to inflammation and NF-κB activation is characterized by the induction of adhesion molecules promoting binding and transmigration of leukocytes, while simultaneously increasing their thrombogenic potential. Paracrine signaling from endothelial cells activates NF-κB in vascular smooth muscle cells and causes a phenotypic switch to a “synthetic” state associated with a decrease in contractile proteins. Monocytes react to inflammatory situations with enforced expression of tissue factor and after differentiation to macrophages with altered polarization. Neutrophils respond with an extension of their life span—and upon full activation they can expel their DNA thereby forming so-called neutrophil extracellular traps (NETs), which exert antibacterial functions, but also induce a strong coagulatory response. This may cause formation of microthrombi that are important for the immobilization of pathogens, a process designated as immunothrombosis. However, deregulation of the complex cellular links between inflammation and thrombosis by unrestrained NET formation or the loss of the endothelial layer due to mechanical rupture or erosion can result in rapid activation and aggregation of platelets and the manifestation of thrombo-inflammatory diseases. Sepsis is an important example of such a disorder caused by a dysregulated host response to infection finally leading to severe coagulopathies. NF-κB is critically involved in these pathophysiological processes as it induces both inflammatory and thrombotic responses.

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“…Increased angiogenesis was also seen in these patients [5]. Increased cytokines are released, such as interleukin (IL)-6, and various acute-phase reactants in COVID-19 can lead to endothelial injury [6]. Reports also suggest activation of alternate and lectin complement pathways (C 5b-9 [membrane attack complex], C4d, and mannose-binding proteinassociated serine protease 2 [MASP2]), leading to further endothelial cell injury [7].…”

Section: Pathogenesismentioning

confidence: 99%

Current Overview on Hypercoagulability in COVID-19

Singhania

Bansal

Nimmatoori

et al. 2020

Am J Cardiovasc Drugs

171

232

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The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has brought many unique pathologies, such as coagulopathy, prompting a desperate need for effective management. COVID-19-associated coagulopathy (CAC) can cause various thromboembolic complications, especially in critically ill patients. The pathogenesis is likely due to endothelial injury, immobilization, and an increase in circulating prothrombotic factors. Data on treatment are limited, although prophylactic anticoagulation is advised in all hospitalized patients. Herein, we have comprehensively reviewed the current literature available on CAC and highlight the pathogenesis, clinical features, and management of CAC. Key Messages Venous thromboembolism (VTE) is common in COVID-19 patients, especially those in the intensive care unit. Prophylactic anticoagulation is recommended in all patients with COVID-19 unless contraindicated.

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The Factor VIII Acute Phase Response Requires the Participation of NFκB and C/EBP

Cited by 71 publications

References 36 publications

A Case Control Study to Evaluate the Impact of Colchicine on Patients Admitted to the Hospital with Moderate to Severe COVID-19 Infection

A Case Control Study to Evaluate the Impact of Colchicine on Patients Admitted to the Hospital with Moderate to Severe COVID-19 Infection

Cell Type-Specific Roles of NF-κB Linking Inflammation and Thrombosis

Current Overview on Hypercoagulability in COVID-19

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