J 2024

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

VÍTEČEK, Jan, Andrea VÍTEČKOVÁ WÜNSCHOVÁ, Sandra THALEROVÁ, Sumeet GULATI, Lukáš KUBALA et. al.

Basic information

Original name

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

Authors

VÍTEČEK, Jan (203 Czech Republic), Andrea VÍTEČKOVÁ WÜNSCHOVÁ (203 Czech Republic, belonging to the institution), Sandra THALEROVÁ (203 Czech Republic, belonging to the institution), Sumeet GULATI (826 United Kingdom of Great Britain and Northern Ireland), Lukáš KUBALA (203 Czech Republic), Michaela CAPANDOVÁ (203 Czech Republic, belonging to the institution), Aleš HAMPL (203 Czech Republic, belonging to the institution) and Robert MIKULÍK (203 Czech Republic)

Edition

PLOS ONE, SAN FRANCISCO, PUBLIC LIBRARY SCIENCE, 2024, 1932-6203

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30210 Clinical neurology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 3.700 in 2022

Organization unit

Faculty of Medicine

UT WoS

001241954400011

Keywords in English

Blood Coagulation; Erythrocytes; Ischemic Stroke; Tissue Plasminogen Activator

Tags

International impact, Reviewed
Změněno: 1/7/2024 14:11, Mgr. Tereza Miškechová

Abstract

V originále

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.

Links

MUNI/A/1598/2023, interní kód MU
Name: Zdroje pro tkáňové inženýrství 14
Investor: Masaryk University, Resources pro tissue engineering 14
NU22-08-00124, research and development project
Name: Modelování toku v intrakraniálních cévách ve vztahu ke změnám endotelu a rozvoji intrakraniálních aneuryzmat
Investor: Ministry of Health of the CR, Subprogram 1 - standard