Altered fibrin clot structure contributes to thrombosis risk in severe COVID-19

Wygrecka, Małgorzata; Birnhuber, Anna; Seeliger, Benjamin; Michalick, Laura; Pak, Oleg; Schultz, Astrid-Solveig; Schramm, Fabian; Zacharias, Martin; Gorkiewicz, Gregor; David, Sascha; Welte, Tobias; Schmidt, Julius J.; Weißmann, Norbert; Schermuly, Ralph T.; Barreto, Guillermo; Schäfer, Liliana; Markart, Philipp; Brack, Markus C.; Hippenstiel, Stefan; Kurth, Florian; Sander, Leif Erik; Witzenrath, Martin; Kuebler, Wolfgang M.; Kwapiszewska, Grażyna; Preissner, Klaus T.

doi:10.1101/2021.09.17.460777

Cited by 2 publications

(3 citation statements)

References 64 publications

(67 reference statements)

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“…FXII was reduced, plasma kallikrein-like activity and HK cleavage products were increased in COVID-19 patients in comparison to influenza ARDS and controls. This shows the decrease in FXII is due to activation (34). A similar pattern of decreased FXII, PKa and HK was reported in a study of 66 intensive care COVID-19 patients (35).…”

Section: The Contact System and Kallikrein Kinin Systemsupporting

confidence: 84%

“…Wygrecka et al compared the levels of factor XII (FXII) and its activation products from critically ill COVID-19 patients with samples from influenza patients with severe ARDS (34). FXII was reduced, plasma kallikrein-like activity and HK cleavage products were increased in COVID-19 patients in comparison to influenza ARDS and controls.…”

Section: The Contact System and Kallikrein Kinin Systemmentioning

confidence: 99%

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Vascular risk factors for COVID-19 ARDS: endothelium, contact-kinin system

et al. 2023

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SARS-CoV-2 binds to ACE2 receptors, expressed within the lungs. Risk factors for hospitalization include hypertension, diabetes, ischaemic heart disease and obesity–conditions linked by the presence of endothelial pathology. Viral infection in this setting causes increased conversion of circulating Factor XII to its active form (FXIIa). This is the first step in the contact-kinin pathway, leading to synchronous activation of the intrinsic coagulation cascade and the plasma Kallikrein-Kinin system, resulting in clotting and inflammatory lung disease. Temporal trends are evident from blood results of hospitalized patients. In the first week of symptoms the activated partial thromboplastin time (APTT) is prolonged. This can occur when clotting factors are consumed as part of the contact (intrinsic) pathway. Platelet counts initially fall, reflecting their consumption in coagulation. Lymphopenia occurs after approximately 1 week, reflecting the emergence of a lymphocytic pneumonitis [COVID-19 acute respiratory distress syndrome (ARDS)]. Intrinsic coagulation also induces the contact-kinin pathway of inflammation. A major product of this pathway, bradykinin causes oedema with ground glass opacities (GGO) on imaging in early COVID-19. Bradykinin also causes release of the pleiotrophic cytokine IL-6, which causes lymphocyte recruitment. Thromobosis and lymphocytic pneumonitis are hallmark features of COVID-19 ARDS. In this review we examine the literature with particular reference to the contact-kinin pathway. Measurements of platelets, lymphocytes and APTT should be undertaken in severe infections to stratify for risk of developing ARDS.

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Section: The Contact System and Kallikrein Kinin Systemsupporting

confidence: 84%

Section: The Contact System and Kallikrein Kinin Systemmentioning

confidence: 99%

Vascular risk factors for COVID-19 ARDS: endothelium, contact-kinin system

et al. 2023

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“…3B). Serpine-1 encodes plasminogen activator inhibitor-1 (PAI-1), an inhibitor of fibrinolysis, which inhibits clot breakdown and pushes the coagulation system in a pro-coagulant direction (16).…”

Section: Discussionmentioning

confidence: 99%

Acute Vaping of a golden Syrian Hamster is Feasible and Leads to Nicotine-Dependent Respiratory Tract Inflammation

Hinds

Nick

Vallin

et al. 2022

Preprint

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IntroductionE-cigarette vaping has become a major portion of nicotine consumption, especially for children and young adults. Although it is branded as a safer alternative to cigarette smoking, murine and rat models of sub-acute and chronic e-cigarette vaping exposure have shown many pro-inflammatory changes in the respiratory tract. An acute vaping exposure paradigm has not been demonstrated in the golden Syrian hamster, and the hamster is a readily available small animal model that has the unique benefit of becoming infected with and transmitting SARS-CoV-2 without genetic alteration to the animal or virus.MethodsUsing a two-day, whole-body vaping exposure protocol in male golden Syrian hamsters, we evaluated serum cotinine, bronchoalveolar lavage cells, lung and nasal histopathology, and gene expression in the nasopharynx and lung through RT-qPCR. Depending on the presence of nonnormality or outliers, statistical analysis was performed by ANOVA or Kruskal-Wallis tests. For tests that were statistically significant (p-value <0.05), post-hoc Tukey-Kramer and Dunn’s tests, respectively, were performed to make pairwise comparisons between groups.ResultsIn nasal tissue, RT-qPCR analysis revealed nicotine-dependent increases in genes associated with type 1 inflammation (CCL-5 and CXCL-10), fibrosis (TGF-β), and a nicotine-independent decrease in the vasculogenesis/angiogenesis gene VEGF-A. In the lung, nicotine-dependent increases in the expression of genes involved in the renin-angiotensin pathway (ACE, ACE2), coagulation (tissue factor, Serpine-1), extracellular matrix remodeling (MMP-2, MMP-9), type 1 inflammation (IL-1β, TNF-α, and CXCL-10), fibrosis (TGF-β and Serpine-1), oxidative stress response (SOD-2), neutrophil extracellular traps release (ELANE), and vasculogenesis and angiogenesis (VEGF-A) were identified.ConclusionTo our knowledge, this is the first demonstration that the Syrian hamster is a viable model of e-cig induced inhalational injury. In addition, this is the first report that e-cig vaping with nicotine can increase tissue factor gene expression in the lung. Our results show that even an acute exposure to e-cigarette vaping causes significant upregulation in the respiratory tract of pathways involving the renin-angiotensin system, coagulation, extracellular matrix remodeling, type 1 inflammation, fibrosis, oxidative stress response, NETosis, vasculogenesis, and angiogenesis.

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Altered fibrin clot structure contributes to thrombosis risk in severe COVID-19

Cited by 2 publications

References 64 publications

Vascular risk factors for COVID-19 ARDS: endothelium, contact-kinin system

Vascular risk factors for COVID-19 ARDS: endothelium, contact-kinin system

Acute Vaping of a golden Syrian Hamster is Feasible and Leads to Nicotine-Dependent Respiratory Tract Inflammation

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