In vitro examination of the thrombolytic efficacy of tenecteplase and therapeutic ultrasound compared to rt-PA

• Main Authors: Tobias Frühwald, Ulrich Gärtner, Nils Stöckmann, Jan-Henning Marxsen, Carolin Gramsch, Florian C. Roessler
• Format: Article
• Language: English
• Published: BMC 2019-08-01
• Series: BMC Neurology
• Subjects: Stroke; Thrombolysis; Tenecteplase; Ultrasound; Transmission electron microscopy
• Online Access: http://link.springer.com/article/10.1186/s12883-019-1404-5

Abstract Background Optimizing thrombolytic therapy is vital for improving stroke outcomes. We aimed to develop standardized thrombolysis conditions to evaluate the efficacy of tenecteplase (TNK) compared to the current gold standard rt-PA (alteplase), with and without additional ultrasound treatment. We also wanted to introduce a new analytical approach to quantify fibrin fiber density in transmission electron microscopy (TEM). Methods In vitro clots that are similar to ex vivo clots concerning their histological condition and their durability were generated from whole blood. For five treatment groups we compared relative clot weight loss (each n = 60) and fibrin fiber density in TEM (each n = 5). The control group (A) was treated only with plasma. Two groups were designated for each rt-PA (B + C) and TNK (D + E). Groups C and E were additionally treated with ultrasound. Dosages were 50 μg/ml for rt-PA and 30 μg/ml for TNK. Results were evaluated by using analyses of variance (ANOVA) and post-hoc t-tests. Results Weight loss was increased significantly for all groups compared to the control group. Both TNK groups showed significantly increased weight loss compared to their counterpart rt-PA group (p ≤ 0.001). For TEM only group D showed significantly decreased fibrin fiber density (p < 0.05) compared to both rt-PA groups. Ultrasound did not significantly increase dissolution of clots with either method (best p = 0.16). Conclusions Tenecteplase dissolved clots more effectively than rt-PA with and without ultrasound. A higher sample size could provide more convincing results for TEM.