Abstract
BackgroundOptimizing 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).MethodsIn 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.ResultsWeight 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).ConclusionsTenecteplase dissolved clots more effectively than rt-PA with and without ultrasound. A higher sample size could provide more convincing results for TEM.
Highlights
Optimizing thrombolytic therapy is vital for improving stroke outcomes
For Recombinant tissue plasminogen activator (rt-PA) we observed a plateau of weight loss between 40 and 50 μg/ml (Fig. 1)
We found one study performed on patients with acute myocardial infarction, showing rt-PA concentration to be at about 3 μg/ml at the steady state after intravenous administration [26]
Summary
Optimizing thrombolytic therapy is vital for improving stroke outcomes. Stroke remains one of the leading causes of death and serious long time disability in the world. Stroke is a clinically and epidemiologically highly relevant and impactful disease, and will remain so in the near future. Thrombectomy is an addition and not a replacement to intravenous thrombolytic therapy. Concerning thrombolytic drugs, rt-PA (Actilyse®) remains the standard treatment within 4.5 h of stroke onset, regardless of severity. Rt-PA offers significant drawbacks, such as the risk of intracranial hemorrhages following treatment and a still limited time window for treatment post onset of symptoms [3] even if this time window is likely to open further [4].
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