Abstract
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, 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.
Highlights
Venous thromboembolism is a significant source of morbidity and mortality worldwide
Primary findings indicate that collagen increased and erythrocytes decreased with thrombus age, and the presence of the fibrinolysis inhibitors plasminogen activator inhibitor 1, alpha 2-antiplasmin, and thrombin-activatable fibrinolysis inhibitor in samples
Ultrasound shear wave elastography was used to assess the elastic modulus of the sample, and the MRI sequence quantitative susceptibility mapping to gauge the fraction of erythrocytes in the sample
Summary
Venous thromboembolism is a significant source of morbidity and mortality worldwide. Catheterdirected thrombolytics is the primary treatment used to relieve critical obstructions, though its efficacy varies based on the thrombus composition. Thrombus samples extracted from venous thromboembolism patients were analyzed ex vivo to determine their histological properties, susceptibility to lytic therapy, and imaging characteristics. 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. The extended treatment time increases the risk of serious bleeding complications associated with rt-PA24 and healthcare costs Alternative interventions such as mechanical extraction[25,26] or histotripsy-aided thrombolysis[27] can be effective for thrombi non-responsive to lytics. The observed changes in clot structure reflect the complex mechanisms by which VTE microstructure may develop lytic resistance, and these mechanisms can be gauged using imaging metrics
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
