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

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.

Základní údaje

Originální název

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

Autoři

VÍTEČEK, Jan (203 Česká republika), Andrea VÍTEČKOVÁ WÜNSCHOVÁ (203 Česká republika, domácí), Sandra THALEROVÁ (203 Česká republika, domácí), Sumeet GULATI (826 Velká Británie a Severní Irsko), Lukáš KUBALA (203 Česká republika), Michaela CAPANDOVÁ (203 Česká republika, domácí), Aleš HAMPL (203 Česká republika, domácí) a Robert MIKULÍK (203 Česká republika)

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30210 Clinical neurology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 3.700 v roce 2022

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.1371/journal.pone.0302269

UT WoS

001241954400011

Klíčová slova anglicky

Blood Coagulation; Erythrocytes; Ischemic Stroke; Tissue Plasminogen Activator

Štítky

14110514, 14110517, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 1. 7. 2024 14:11, Mgr. Tereza Miškechová

Anotace

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.

Návaznosti

MUNI/A/1598/2023, interní kód MU

Název: Zdroje pro tkáňové inženýrství 14

Investor: Masarykova univerzita, Zdroje pro tkáňové inženýrství 14

NU22-08-00124, projekt VaV

Název: Modelování toku v intrakraniálních cévách ve vztahu ke změnám endotelu a rozvoji intrakraniálních aneuryzmat

Investor: Ministerstvo zdravotnictví ČR, Modelování toku v intrakraniálních cévách ve vztahu ke změnám endotelu a rozvoji intrakraniálních aneuryzmat, Podprogram 1 - standardní

Citovat

VÍTEČEK, Jan, Andrea VÍTEČKOVÁ WÜNSCHOVÁ, Sandra THALEROVÁ, Sumeet GULATI, Lukáš KUBALA, Michaela CAPANDOVÁ, Aleš HAMPL a Robert MIKULÍK. Factors influencing the efficacy of recombinant tissue plasminogen activator: Implications for ischemic stroke treatment. PLOS ONE. SAN FRANCISCO: PUBLIC LIBRARY SCIENCE, 2024, roč. 6, č. 19, s. 1-13. ISSN 1932-6203. Dostupné z: https://dx.doi.org/10.1371/journal.pone.0302269.

@article{2409857,
   author = {Víteček, Jan and Vítečková Wünschová, Andrea and Thalerová, Sandra and Gulati, Sumeet and Kubala, Lukáš and Capandová, Michaela and Hampl, Aleš and Mikulík, Robert},
   article_location = {SAN FRANCISCO},
   article_number = {19},
   doi = {http://dx.doi.org/10.1371/journal.pone.0302269},
   keywords = {Blood Coagulation; Erythrocytes; Ischemic Stroke; Tissue Plasminogen Activator},
   language = {eng},
   issn = {1932-6203},
   journal = {PLOS ONE},
   title = {Factors influencing the efficacy of recombinant tissue plasminogen activator: Implications for ischemic stroke treatment},
   url = {https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0302269},
   volume = {6},
   year = {2024}
}

TY  - JOUR
ID  - 2409857
AU  - Víteček, Jan - Vítečková Wünschová, Andrea - Thalerová, Sandra - Gulati, Sumeet - Kubala, Lukáš - Capandová, Michaela - Hampl, Aleš - Mikulík, Robert
PY  - 2024
TI  - Factors influencing the efficacy of recombinant tissue plasminogen activator: Implications for ischemic stroke treatment
JF  - PLOS ONE
VL  - 6
IS  - 19
SP  - 1-13
EP  - 1-13
PB  - PUBLIC LIBRARY SCIENCE
SN  - 19326203
KW  - Blood Coagulation
KW  - Erythrocytes
KW  - Ischemic Stroke
KW  - Tissue Plasminogen Activator
UR  - https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0302269
N2  - 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.
ER  -

VÍTEČEK, Jan, Andrea VÍTEČKOVÁ WÜNSCHOVÁ, Sandra THALEROVÁ, Sumeet GULATI, Lukáš KUBALA, Michaela CAPANDOVÁ, Aleš HAMPL a Robert MIKULÍK. Factors influencing the efficacy of recombinant tissue plasminogen activator: Implications for ischemic stroke treatment. \textit{PLOS ONE}. SAN FRANCISCO: PUBLIC LIBRARY SCIENCE, 2024, roč.~6, č.~19, s.~1-13. ISSN~1932-6203. Dostupné z: https://dx.doi.org/10.1371/journal.pone.0302269.

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