Key result
Low-concentration alteplase induces less lysis in swine versus human clots, but higher concentrations perform equally.
Why the study?
Swine thrombi have different characteristics than human thrombi that may confer greater resistance to fibrinolysis, impacting their use as a translational research model.
Swine blood clots exhibit concentration-dependent resistance to alteplase-induced thrombolysis compared to human clots, requiring higher concentrations for equivalent lysis in translational models.
Answers are grounded in this paper and cite their sources.
May limit swine model applicability for low-dose alteplase; leaves open species-specific validation in translational thrombolysis research.
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. 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. 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). 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.
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Neto‐Neves et al. (2021) studied Blood clots. Alteplase vs. Human blood clots and phosphate-buffered saline was evaluated on Clot lysis (difference between clot mass pre- and post-lysis) (p=<0.05). Alteplase at low concentrations (250–2000 IU/mL) induced significantly less lysis in swine blood clots compared to human blood clots (p<0.05), with equivalent lysis at higher concentrations.
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