The resistance of swine blood clots to alteplase-induced thrombolysis in vitro is concentration-dependent

Abstract

Background: Swine have been used as a large animal translational research model to investigate the effectiveness of fibrinolytic agents. However, swine thrombi have different characteristics than human thrombi, which may confer more resistance to fibrinolysis.

Methods: In this study, we performed an in-vitro clot lysis assay to compare both human and swine blood clots lysis induced by alteplase, a recombinant tissue plasminogen-activator agent. Human and swine whole blood were allowed to clot for 3 ​h at 37 ​°C. Increasing concentrations of alteplase (250–580,000 IU/mL) or phosphate-buffered saline (PBS, pH 7.4) were added into the clots. Clot lysis was determined by calculating the difference between the clot mass pre- and post-lysis.

Results: At low alteplase concentrations (250–2000 IU/mL) we observed significantly less swine blood clot lysis (14 ​± ​1.7% - 35 ​± ​4.9%) compared to the lysis found to human blood clots (52 ​± ​4.8% - 68 ​± ​3.3%, ∗p ​< ​0.05). In contrast, we did not find lysis differences between human and swine clots at higher alteplase concentrations (5000–580,000 IU/mL).

Conclusions: In conclusion, our results suggest that the swine clot resistance to alteplase-induced thrombolysis is concentration-dependent. A high concentration of alteplase allows equivalent thrombolysis of swine and human blood clots in vitro.