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Abstract Vascular hypo‐fibrinolysis is a historically underappreciated and understudied aspect of venous thromboembolism (VTE). This paper describes the development of a micro‐clot dissolution assay for quantifying the fibrinolytic capacity of endothelial cells – a key driver of VTE development. This assay is enabled using aqueous two‐phase systems (ATPS) to bioprint microscale fibrin clots over human umbilical vein endothelial cells (HUVECs). Importantly, these micro‐clots are orders of magnitude smaller than conventional fibrin constructs and allow HUVEC‐produced plasminogen activators to mediate visually quantifiable fibrinolysis. Using live‐cell time‐lapse imaging, micro‐clot dissolution by HUVECs is tracked, and fibrinolysis kinetics are quantified. The sensitivity of cell‐driven fibrinolysis to various stimuli is rapidly tested. The physiological relevance of this convenient high‐throughput assay is illustrated through treatments with lipopolysaccharide (LPS) and rosuvastatin that elicit anti‐ and pro‐fibrinolytic responses, respectively. Furthermore, treatment with baricitinib, an anti‐inflammatory therapeutic found to increase cardiovascular risks after market approval, provokes an anti‐fibrinolytic response – which highlights the potential role of endothelial cells in increasing VTE risk for patients receiving this drug. This endothelial cell fibrinolysis assay provides a high‐throughput and versatile drug testing platform – potentially allowing for early preclinical identification of therapeutics that may beneficially enhance or adversely impair endothelial fibrinolysis.
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Evaluating the Ability of Caprini and Padua Scores to Predict Venous Thromboembolism in a Nationwide Study
Venous thromboembolism (VTE) is a preventable complication of hospitalization. VTE risk-assessment models (RAMs) including the Caprini and Padua RAMs quantify VTE risk based on demographic and clinical characteristics. Both RAMs have performed well in selected high-risk cohorts with relatively small sample sizes but few studies have evaluated the RAMs in large, unselected cohorts. We assessed the ability of both RAMs to predict VTE in a large, nationwide, diverse cohort of surgical and nonsurgical patients.
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- Award ID(s):
- 2051800
- PAR ID:
- 10507571
- Publisher / Repository:
- Society for Vascular Surgery
- Date Published:
- Journal Name:
- Journal of Vascular Surgery: Venous and Lymphatic Disorders
- Volume:
- 11
- Issue:
- 2
- ISSN:
- 2213-333X
- Page Range / eLocation ID:
- 457 to 458
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1016/j.jvsv.2022.12.035
