Factors influencing the efficacy of recombinant tissue plasminogen activator: Implications for ischemic stroke treatment

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Publikace nespadá pod Ekonomicko-správní fakultu, ale pod Lékařskou fakultu. Oficiální stránka publikace je na webu muni.cz.
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VÍTEČEK Jan VÍTEČKOVÁ WÜNSCHOVÁ Andrea THALEROVÁ Sandra GULATI Sumeet KUBALA Lukáš CAPANDOVÁ Michaela HAMPL Aleš MIKULÍK Robert

Rok publikování 2024
Druh Článek v odborném periodiku
Časopis / Zdroj PLOS ONE
Fakulta / Pracoviště MU

Lékařská fakulta

Citace
www https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0302269
Doi http://dx.doi.org/10.1371/journal.pone.0302269
Klíčová slova Blood Coagulation; Erythrocytes; Ischemic Stroke; Tissue Plasminogen Activator
Popis Intravenous thrombolysis with a recombinant tissue plasminogen activator (rt-PA) is the first-line treatment of acute ischemic stroke. However, successful recanalization is relatively low and the underlying processes are not completely understood. The goal was to provide insights into clinically important factors potentially limiting rt-PA efficacy such as clot size, rt-PA concentration, clot age and also rt-PA in combination with heparin anticoagulant. We established a static in vitro thrombolytic model based on red blood cell (RBC) dominant clots prepared using spontaneous clotting from the blood of healthy donors. Thrombolysis was determined by clot mass loss and by RBC release. The rt-PA became increasingly less efficient for clots larger than 50 µl at a clinically relevant concentration of 1.3 mg/l. A tenfold decrease or increase in concentration induced only a 2-fold decrease or increase in clot degradation. Clot age did not affect rt-PA-induced thrombolysis but 2-hours-old clots were degraded more readily due to higher activity of spontaneous thrombolysis, as compared to 5-hours-old clots. Finally, heparin (50 and 100 IU/ml) did not influence the rt-PA-induced thrombolysis. Our study provided in vitro evidence for a clot size threshold: clots larger than 50 µl are hard to degrade by rt-PA. Increasing rt-PA concentration provided limited thrombolytic efficacy improvement, whereas heparin addition had no effect. However, the higher susceptibility of younger clots to thrombolysis may prompt a shortened time from the onset of stroke to rt-PA treatment.
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