Assessment of histological characteristics, imaging markers, and rt-PA susceptibility of ex vivo venous thrombi

• Published in: Scientific reports Vol. 11; no. 1; pp. 22805 - 12
• Main Authors: Hendley, Samuel A., Dimov, Alexey, Bhargava, Aarushi, Snoddy, Erin, Mansour, Daniel, Afifi, Rana O., Wool, Geoffrey D., Zha, Yuanyuan, Sammet, Steffen, Lu, Zheng Feng, Ahmed, Osman, Paul, Jonathan D., Bader, Kenneth B.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23-11-2021; Nature Publishing Group; Nature Portfolio
• Subjects: 692/308/53/2423; 692/4019/592; Biomarkers - metabolism; Blood clots; Catheters; Clinical outcomes; Elasticity Imaging Techniques - methods; Fibrin; Fibrinolytic Agents - administration & dosage; Humanities and Social Sciences; Humans; Magnetic resonance imaging; Medical instruments; Morbidity; multidisciplinary; Science; Science (multidisciplinary); Thromboembolism; Thrombosis; Tissue Plasminogen Activator - administration & dosage; Ultrasonography - methods; Venous Thrombosis - drug therapy; Venous Thrombosis - metabolism; Venous Thrombosis - pathology
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-02030-7

Venous thromboembolism is a significant source of morbidity and mortality worldwide. Catheter-directed thrombolytics is the primary treatment used to relieve critical obstructions, though its efficacy varies based on the thrombus composition. Non-responsive portions of the specimen often remain in situ
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which prohibits mechanistic investigation of lytic resistance or the development of diagnostic indicators for treatment outcomes. In this study, thrombus samples extracted from venous thromboembolism patients were analyzed ex vivo to determine their histological properties, susceptibility to lytic therapy, and imaging characteristics. A wide range of thrombus morphologies were observed, with a dependence on age and etymology of the specimen. Fibrinolytic inhibitors including PAI-1, alpha 2-antiplasmin, and TAFI were present in samples, which may contribute to the response venous thrombi to catheter-directed thrombolytics. Finally, a weak but significant correlation was observed between the response of the sample to lytic drug and its magnetic microstructure assessed with a quantitative MRI sequence. These findings highlight the myriad of changes in venous thrombi that may promote lytic resistance, and imaging metrics that correlate with treatment outcomes.