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.

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:

URL

Impact factor

Impact factor: 3.700 in 2022

Organization unit

Faculty of Medicine

DOI

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

UT WoS

001241954400011

Keywords in English

Blood Coagulation; Erythrocytes; Ischemic Stroke; Tissue Plasminogen Activator

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

Citovat

VÍTEČEK, Jan, Andrea VÍTEČKOVÁ WÜNSCHOVÁ, Sandra THALEROVÁ, Sumeet GULATI, Lukáš KUBALA, Michaela CAPANDOVÁ, Aleš HAMPL and Robert MIKULÍK. Factors influencing the efficacy of recombinant tissue plasminogen activator: Implications for ischemic stroke treatment. PLOS ONE. SAN FRANCISCO: PUBLIC LIBRARY SCIENCE, 2024, vol. 6, No 19, p. 1-13. ISSN 1932-6203. Available from: 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 and 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, vol.~6, No~19, p.~1-13. ISSN~1932-6203. Available from: https://dx.doi.org/10.1371/journal.pone.0302269.

Detailed Information on Publication Record