Platelet hyperaggregability is associated with decreased ADAMTS13 activity and enhanced endotoxemia in patients with acute cholangitis

Takaya, Hiroaki; Kawaratani, Hideto; Kubo, Takuya; Seki, Kazuhiko; Sawada, Yasuhiko; Kaji, Kosuke; Okada, Yasushi; Takeda, Kosuke; Kitade, Mitsuteru; Moriya, Kyoji; Namisaki, Tadashi; Mitoro, Akira; Matsumoto, Masanori; Fukui, Hiroshi; Yoshiji, Hitoshi

doi:10.1111/hepr.12926

Cited by 13 publications

(21 citation statements)

References 31 publications

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“…Despite playing an important role in the maintenance of hemostasis and the occurrence of micro-and macrovascular thrombosis, VWF-ADAMTS-13 interactions have not received much investigative attention in the evaluation of COVID-19 pathophysiology, specifically in relation to elevated incidence of VTE. Importantly, reduced ADAMTS-13 activity has been shown to correlate with increased inflammation in multiple sys-tems, [100][101][102] while IL-6 has been shown to inhibit the cleavage of ultra-large VWF strings by ADAMTS-13 under flowing conditions. 79,103 The authors could find only five studies evaluating both VWF and ADAMTS-13 levels in COVID-19 patients in literature [104][105][106][107][108] (►Table 3).…”

Section: Vwf-adamts-13 Interactions In Covid-19mentioning

confidence: 99%

Coagulopathy and Thrombosis as a Result of Severe COVID-19 Infection: A Microvascular Focus

et al. 2020

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Coronavirus disease of 2019 (COVID-19) is the clinical manifestation of the respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While primarily recognized as a respiratory disease, it is clear that COVID-19 is systemic illness impacting multiple organ systems. One defining clinical feature of COVID-19 has been the high incidence of thrombotic events. The underlying processes and risk factors for the occurrence of thrombotic events in COVID-19 remain inadequately understood. While severe bacterial, viral, or fungal infections are well recognized to activate the coagulation system, COVID-19-associated coagulopathy is likely to have unique mechanistic features. Inflammatory-driven processes are likely primary drivers of coagulopathy in COVID-19, but the exact mechanisms linking inflammation to dysregulated hemostasis and thrombosis are yet to be delineated. Cumulative findings of microvascular thrombosis has raised question if the endothelium and microvasculature should be a point of investigative focus. von Willebrand factor (VWF) and its protease, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS-13), play important role in the maintenance of microvascular hemostasis. In inflammatory conditions, imbalanced VWF-ADAMTS-13 characterized by elevated VWF levels and inhibited and/or reduced activity of ADAMTS-13 has been reported. Also, an imbalance between ADAMTS-13 activity and VWF antigen is associated with organ dysfunction and death in patients with systemic inflammation. A thorough understanding of VWF-ADAMTS-13 interactions during early and advanced phases of COVID-19 could help better define the pathophysiology, guide thromboprophylaxis and treatment, and improve clinical prognosis.

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Section: Vwf-adamts-13 Interactions In Covid-19mentioning

confidence: 99%

Coagulopathy and Thrombosis as a Result of Severe COVID-19 Infection: A Microvascular Focus

et al. 2020

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“…The tumor microenvironment, notably including the surrounding blood vessels; the hepatic non-parenchymal cells, such as Kupffer cells, hepatic stellate cells (HSCs), liver sinusoidal endothelial cells; and the diverse types of lymphocytes, plays a crucial role in tumor initiation and progression in HCC [11]. A disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13 (ADAMTS13) is predominantly produced in HSCs and cleaves newly secreted, unusually large von Willebrand factor (VWF) multimers (UL-VWFM) on the endothelial surface under high shear stress [12–14]. An imbalance between ADAMTS13 activity and UL-VWFM, formed by endothelial cell (EC) secretion of VWF from the endothelial surface, triggers thrombosis by inducing platelet adhesion and aggregation [15].…”

Section: Introductionmentioning

confidence: 99%

VWF/ADAMTS13 ratio as a potential biomarker for early detection of hepatocellular carcinoma

et al. 2019

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Background To investigate the von Willebrand factor to ADAMTS13 ratio as a potential biomarker for early detection of hepatocellular carcinoma (HCC) in cirrhosis. Methods Serum levels of alpha-fetoprotein, des-γ-carboxy prothrombin, Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (alpha-fetoprotein-L3%), vascular endothelial growth factor, and vascular endothelial growth factor receptor-2, as well as the plasma levels of von Willebrand factor antigen (von Willebrand factor: Ag) and ADAMTS13 activity (ADAMTS13:AC), were evaluated in 41 cirrhotic patients with HCC undergoing radiofrequency ablation and in 20 cirrhotic patients without HCC. The diagnostic accuracy of each biomarker was evaluated using the receiver operating characteristic curve analysis. Results The von Willebrand factor: Ag and von Willebrand factor: Ag/ADAMTS13:AC ratios were significantly higher in cirrhotic patients with HCC than in those without HCC (p < 0.05 and p < 0.01, respectively), whereas ADAMTS13:AC was significantly lower in those with HCC than those without HCC (p < 0.05). However, no relationship was observed between the von Willebrand factor: Ag/ADAMTS13:AC ratio and serum tumor markers such as alpha-fetoprotein, des-γ-carboxy prothrombin, and alpha-fetoprotein-L3%. Multivariate regression analysis identified von Willebrand factor: Ag/ADAMTS13:AC ratio and alpha-fetoprotein-L3% as significant factors of HCC development. Receiver operating characteristic analysis showed that the von Willebrand factor: Ag/ADAMTS13:AC ratio and alpha-fetoprotein-L3% had a better performance than alpha-fetoprotein, des-γ-carboxy prothrombin, alpha-fetoprotein-L3%, vascular endothelial growth factor, and vascular endothelial growth factor receptor-2, von Willebrand factor: Ag, and ADAMTS13:AC. The von Willebrand factor: Ag/ADAMTS13:AC ratio was exclusively correlated with tumor volume and stage as well as serum vascular endothelial growth factor levels. Conclusions The von Willebrand factor: Ag/ADAMTS13:AC ratio can potentially serve as a novel biomarker for early diagnosis of HCC in cirrhotic patients.

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“…Despite playing an important role in the maintenance of hemostasis and prevention of undesirable thrombosis, VWF-ADAMTS13 interactions haven't received much attention in the evaluation of COVID-19 pathophysiology, specifically VTE. Importantly, reduced ADAMTS13 activity has been shown to correlate with increased inflammation in multiple systems (75)(76)(77), while IL-6 has been shown to inhibit the cleavage of ultra-large VWF strings by ADAMTS13 under flowing conditions (62,78). The authors could find only two studies evaluating VWF in COVID-19 patients in literature (7,79).…”

Section: Vwf-adamts13 Interactions In Covid-19mentioning

confidence: 99%

Consumptive Coagulopathy and Thrombosis during Severe COVID-19 Infection: Potential Involvement of VWF/ADAMTS13

Katneni¹,

Alexaki²,

Hunt³

et al. 2020

Preprint

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Coronavirus disease of 2019 (COVID-19) is the clinical manifestation of the respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Following its origin as a regional outbreak in Wuhan, China, COVID-19 rapidly spread globally and eventually was designated as pandemic by the World Health Organization. Multiple studies describing the clinical characteristics of COVID-19 patients highlighted the prevalence of abnormal coagulopathy and higher incidence of thrombosis. These studies identified co-morbid inflammatory disorders as risk factors for hospitalization in SARS-CoV-2 infections. While early evidence suggested inflammatory conditions as the leading cause of abnormal coagulopathy in COVID-19 patients, the mechanisms behind progression of inflammation mediated hemostasis dysregulation to thrombotic outcomes in susceptible individuals are not well understood. In addition, a sensitive and temporal assessments of coagulation and fibrinolysis is still lacking. Von Willebrand Factor (VWF) and ADAMTS13 interactions play an important role in the maintenance of hemostasis and prevention of unwanted thrombosis. In inflammatory conditions, VWF-ADAMTS13 imbalance characterized by elevated VWF levels and inhibited and/or reduced activity of ADAMTS13 is reported. Also, an imbalance between ADAMTS13 activity and VWF antigen is associated with organ dysfunction and death in patients with systemic inflammation. Despite the natural antithrombotic activity of ADAMTS13, its role in COVID-19 pathophysiology, specifically thrombotic outcomes has not yet been investigated. A thorough understanding of VWF-ADAMTS13 interactions during early and advanced phases of COVID-19 could help define the pathophysiology, guide thromboprophylaxis and treatment and improve clinical prognosis.

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Platelet hyperaggregability is associated with decreased ADAMTS13 activity and enhanced endotoxemia in patients with acute cholangitis

Cited by 13 publications

References 31 publications

Coagulopathy and Thrombosis as a Result of Severe COVID-19 Infection: A Microvascular Focus

Coagulopathy and Thrombosis as a Result of Severe COVID-19 Infection: A Microvascular Focus

VWF/ADAMTS13 ratio as a potential biomarker for early detection of hepatocellular carcinoma

Consumptive Coagulopathy and Thrombosis during Severe COVID-19 Infection: Potential Involvement of VWF/ADAMTS13

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