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

• Published in: Thrombosis update Vol. 2; p. 100035
• Main Authors: Neto-Neves, Evandro M., Beam, Daren M., Kline, Jeffrey A.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 2021; Elsevier
• Subjects: Alteplase; Human blood clots; Swine blood clots; Thrombolysis resistance; Tissue plasminogen-activator; Human blood clots; Swine blood clots; Alteplase; Thrombolysis resistance; Tissue plasminogen-activator
• ISSN: 2666-5727; 2666-5727
• DOI: 10.1016/j.tru.2021.100035

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. •A large animal model of pulmonary embolism is needed to better study the pathophysiology of acute pulmonary embolism and effect of reperfusion therapy.•Lack of a viable model to study fibrinolysis remains one barrier.•In a swine autologous clot model of PE, we found that human recombinant tPA can produce fibrinolysis, but only at a high dose.