Inflammatory cytokines in type 2 diabetes mellitus as facilitators of hypercoagulation and abnormal clot formation

Randeria, Shehan; Thomson, Greig J. A.; Nell, Theo; Roberts, Timothy J.; Pretorius, Etheresia

doi:10.1186/s12933-019-0870-9

Cited by 138 publications

(104 citation statements)

References 83 publications

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“…Fibrinogen is a large, extracellular protein, synthesised by the liver and mainly found in the blood [33][34][35]. Fibrinogen is also an acute-phase protein that is upregulated during inflammation [33,36,37]. Upregulation of fibrin(ogen) is associated with hypercoagulability and endothelial dysfunction.…”

Section: Introductionmentioning

confidence: 99%

Covid-19: The Rollercoaster of Fibrin(Ogen), D-Dimer, Von Willebrand Factor, P-Selectin and Their Interactions with Endothelial Cells, Platelets and Erythrocytes

Grobler

Grobbelaar

Maphumulo

et al. 2020

IJMS

Self Cite

167

154

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Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), also known as coronavirus disease 2019 (COVID-19)-induced infection, is strongly associated with various coagulopathies that may result in either bleeding and thrombocytopenia or hypercoagulation and thrombosis. Thrombotic and bleeding or thrombotic pathologies are significant accompaniments to acute respiratory syndrome and lung complications in COVID-19. Thrombotic events and bleeding often occur in subjects with weak constitutions, multiple risk factors and comorbidities. Of particular interest are the various circulating inflammatory coagulation biomarkers involved directly in clotting, with specific focus on fibrin(ogen), D-dimer, P-selectin and von Willebrand Factor (VWF). Central to the activity of these biomarkers are their receptors and signalling pathways on endothelial cells, platelets and erythrocytes. In this review, we discuss vascular implications of COVID-19 and relate this to circulating biomarker, endothelial, erythrocyte and platelet dysfunction. During the progression of the disease, these markers may either be within healthy levels, upregulated or eventually depleted. Most significant is that patients need to be treated early in the disease progression, when high levels of VWF, P-selectin and fibrinogen are present, with normal or slightly increased levels of D-dimer (however, D-dimer levels will rapidly increase as the disease progresses). Progression to VWF and fibrinogen depletion with high D-dimer levels and even higher P-selectin levels, followed by the cytokine storm, will be indicative of a poor prognosis. We conclude by looking at point-of-care devices and methodologies in COVID-19 management and suggest that a personalized medicine approach should be considered in the treatment of patients.

show abstract

Section: Introductionmentioning

confidence: 99%

Covid-19: The Rollercoaster of Fibrin(Ogen), D-Dimer, Von Willebrand Factor, P-Selectin and Their Interactions with Endothelial Cells, Platelets and Erythrocytes

Grobler

Grobbelaar

Maphumulo

et al. 2020

IJMS

Self Cite

167

154

View full text Add to dashboard Cite

show abstract

“…Fibrinogen is a large, extracellular protein, synthesised by the liver and mainly found in the blood [31][32][33].) Fibrinogen (normal levels between 2 -4 mg/mL) is also an acute-phase protein that is upregulated during inflammation [31,34,35]. Upregulation of fibrin(ogen) is associated with hypercoagulability and endothelial dysfunction.…”

Section: Introductionmentioning

confidence: 99%

COVID-19: The Rollercoaster of Fibrin(ogen), D-dimer, von Willebrand Factor, P-selectin and Their Interactions with Endothelial Cells, Platelets and Erythrocytes

Grobler¹,

Bredenkamp²,

Grobbelaar³

et al. 2020

Preprint

Self Cite

107

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Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), coronavirus disease 2019 (COVID-19)-induced infection is strongly associated with various coagulopathies that may result in either bleeding and thrombocytopenia or hypercoagulation and thrombosis. Thrombotic and bleeding or thrombotic pathologies are significant accompaniments to acute respiratory syndrome and lung complications in COVID-19. Thrombotic events and bleeding, often occurs in subjects with weak multiple risk factors and co-morbidities. Of particular interest are the various circulating inflammatory coagulation biomarkers involved directly in clotting, with specific focus on fibrin(ogen), D-dimer, P-selectin and von Willebrand Factor (vWF). Central to activity of these biomarkers are their receptors and signaling pathways on endothelial cells, platelets and erythrocytes. In this review, we discuss vascular implications of COVID-19, and relate this to circulating biomarker, endothelial, erythrocyte and platelet dysfunction. During the progression of the disease, these markers may either be within healthy levels, upregulated or eventually depleted. Most significant is that patients need to be treated early in the disease progression, when high levels of vWF, P-selectin and fibrinogen are present with still low levels of D-dimer. Progression to vWF and fibrinogen depletion with high D-dimer levels and even higher P-selectin levels, followed by the cytokine storm, will be indicative of a poor prognosis. We conclude by looking at point-of-care devises and methodologies in COVID-19 management and suggest that a personalized medicine approach should be considered in the treatment of patients.

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“…In previous research, women have been reported to have a decrease in ammatory response in comparison to men due to a rapid decline in sex-steroid during reproductive senescence [24]. Previously, researchers often combine men and women into control and experimental groups [26][27][28]. When we combine men and women in the control and experimental, there is no difference between participants with normal and high HbA1c (Fig.…”

Section: Discussionmentioning

confidence: 93%

Sex-specific Relationships Between Il-3, Il-7 and Lipids in African Americans

Williams¹,

Wooten²,

Melendez³

et al. 2020

Preprint

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Purpose: Obesity, a complex chronic disorder characterized by the enlargement of adipose tissue, has a multifactorial etiology. Adipose tissue is now recognized as an active tissue in the regulation of inflammation. Sex chromosome genes and hormones influences immune responses between males and females. Inflammation is rampant in obesity due to the expansion of visceral adipose tissue leading to insulin resistance resulting in type-2 diabetes (T2D). Differences in sex may lead to varied immune responses to T2D.Methods: A total of 116 serum samples were collected from African Americans: 68 women and 48 men. All participants had a BMI > 30. This group consists of 49 normal HbA1c and 71 high HbA1c participants. This study was designed to determine the impact of current circulating glucose on current serum IL-3 and IL-7 levels.Results:Serum cytokine levels are influenced by circulating high glucose and it varies based on sex. We found in women, IL-3 and IL-7 levels were upregulated 1.7-fold in the presence of high circulating glucose. In men, IL-3 levels were downregulated 1.5-fold and IL-7 levels downregulated 1.3-fold in the presence of high circulating glucose. IL-3 and IL-7 serum levels are also correlated with several lipid parameters.Conclusion: IL-3 and IL-7 are members of a complex network of cytokines that play a role in chronic inflammation. Inflammatory signaling impact several diseases including obesity, T2D, atherosclerosis and dyslipidemia. A better understanding of the pathological signaling of cytokines will help facilitate our understanding of inflammation in these diseases.

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Inflammatory cytokines in type 2 diabetes mellitus as facilitators of hypercoagulation and abnormal clot formation

Cited by 138 publications

References 83 publications

Covid-19: The Rollercoaster of Fibrin(Ogen), D-Dimer, Von Willebrand Factor, P-Selectin and Their Interactions with Endothelial Cells, Platelets and Erythrocytes

Covid-19: The Rollercoaster of Fibrin(Ogen), D-Dimer, Von Willebrand Factor, P-Selectin and Their Interactions with Endothelial Cells, Platelets and Erythrocytes

COVID-19: The Rollercoaster of Fibrin(ogen), D-dimer, von Willebrand Factor, P-selectin and Their Interactions with Endothelial Cells, Platelets and Erythrocytes

Sex-specific Relationships Between Il-3, Il-7 and Lipids in African Americans

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