Artikel
Comparative analysis of fibrinolytic properties of rtPA, Tenecteplase and Urokinase in a clot model of intracerebral haemorrhage
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Autoren
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Naureen Keric
- Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Klinik und Poliklinik für Neurochirurgie, Mainz, Deutschland
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Melanie Döbel
- Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Klinik und Poliklinik für Neurochirurgie, Mainz, Deutschland
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Axel Heimann
- Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Neurochirurgische Pathophysiologie, Mainz, Deutschland
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Sven Rainer Kantelhardt
- Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Klinik und Poliklinik für Neurochirurgie, Mainz, Deutschland
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Florian Ringel
- Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Klinik und Poliklinik für Neurochirurgie, Mainz, Deutschland
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Julia Masomi-Bornwasser
- Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Klinik und Poliklinik für Neurochirurgie, Mainz, Deutschland
| Veröffentlicht: | 18. Juni 2018 |
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Gliederung
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Objective: Hematoma lysis with recombinant tissue plasminogen activator (rtPA) has emerged as an alternative therapy for spontaneous intracerebral and intraventricular haemorrhage (ICH and IVH). However the CLEAR III trial failed to show significant improvement of favourable outcomes. Besides experimental and clinical trials revealed neurotoxic effects of rtPA. The demand for optimization of fibrinolytic therapy persists. Herein, we used our recently devised clot model of ICH to systematically analyse fibrinolytic effects of rtPA, Tenecteplase and Urokinase.
Methods: In vitro clots of human blood (size: 25 ml and 50 ml; age: 1.5 h, 24 h and 48 h) were produced and equipped with a catheter into the clot core for drug delivery and drainage. Various doses of Tenecteplase and Urokinase with different treatment periods were examined (all groups n=3 each), assessing the optimal dose and treatment time of these fibrinolytics. Clots were weighed before and at the end of treatment. These results were compared with clots treated with 1 mg rtPA.
Results: The optimal treatment scheme of Tenecteplase was 100 IU with an incubation time of 30 min compared to placebo (P=0.0062). For Urokinase 50000 IU with incubation of 20 and 60 min showed highest lysis rates compared to placebo (P=0.011 and P=0.0015). The relative end weights after the optimal treatment regimens were comparable (rtPA: 36.7 ±10.7%; Tenecteplase: 31.3 ±11.9%; Urokinase (20 min) 34.8 ±7.7% and Urokinase (60 min) 28.9 ±8.9%). Larger clots were more effectively treated with Tenecteplase compared to Urokinase and rtPA (P=0.05). Urokinase and Tenecteplase reached a trend of higher lysis rates in older clots.
Conclusion: In our in vitro clot model we could show optimal treatment regimen of Tenecteplase (100 IU, 30 min) and Urokinase (50000 IU, 20-60 min). These schemes were well comparable in their fibrinolytic potential with 1mg rtPA in small clots. Tenecteplase was more effective in larger clots. These findings are the basis for further in vivo investigations.
