Decreased clot burden is associated with factor XIII Val34Leu polymorphism and better functional outcomes in acute ischemic stroke patients treated with intravenous thrombolysis.

<h4>Background</h4>Intravenous thrombolysis using recombinant tissue plasminogen activator remains the mainstay treatment of acute ischemic stroke (AIS), although endovascular treatment is becoming standard of care in case of large vessel occlusions (LVO). To quantify the thrombus burden...

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Autores principales:	István Szegedi, Rita Orbán-Kálmándi, Attila Nagy, Ferenc Sarkady, Nikolett Vasas, Máté Sik, Levente István Lánczi, Ervin Berényi, László Oláh, Alexandra Crișan, László Csiba, Zsuzsa Bagoly
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f9f2cb92308d4b51b52d72f1094f2e0f
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spelling	oai:doaj.org-article:f9f2cb92308d4b51b52d72f1094f2e0f2021-12-02T20:15:35ZDecreased clot burden is associated with factor XIII Val34Leu polymorphism and better functional outcomes in acute ischemic stroke patients treated with intravenous thrombolysis.1932-620310.1371/journal.pone.0254253https://doaj.org/article/f9f2cb92308d4b51b52d72f1094f2e0f2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0254253https://doaj.org/toc/1932-6203<h4>Background</h4>Intravenous thrombolysis using recombinant tissue plasminogen activator remains the mainstay treatment of acute ischemic stroke (AIS), although endovascular treatment is becoming standard of care in case of large vessel occlusions (LVO). To quantify the thrombus burden in LVO, a semiquantitative CT angiography (CTA) grading system, the clot burden score (CBS) can be used. Here we aimed to study the association between CBS and various hemostasis parameters, and to evaluate which parameters are major determinants of thrombolysis outcome.<h4>Methods</h4>In this single-centered prospective observational case-control study, 200 anterior circulation AIS patients receiving intravenous thrombolysis treatment without thrombectomy were enrolled: 100 AIS patients with LVO (CBS 0-9) and 100 age- and sex-matched AIS patients without LVO (CBS 10). Fibrinogen, α2-plasmin inhibitor, plasminogen, factor XIII and D-dimer were assessed from blood samples taken before and 24 h after thrombolysis, and FXIII-A Val34Leu was genotyped. CBS was calculated using admission CTA. Short-term outcomes were defined based on the change in NIHSS by day 7, long-term outcomes were assessed according to the modified Rankin scale at 3 months post-event.<h4>Results</h4>Poor outcomes were significantly more frequent in the CBS 0-9 group. Plasminogen activity on admission was significantly higher in the CBS 0-9 group. In a univariate analysis, significant protective effect of the Leu34 allele against developing larger clots (CBS 0-9) could be demonstrated (OR:0.519; 95%CI:0.298-0.922, p = 0.0227). Multivariate regression analysis revealed that CBS is an independent predictor of short- and long-term functional outcomes, while such effect of the studied hemostasis parameters could not be demonstrated.<h4>Conclusions</h4>CBS was found to be a significant independent predictor of thrombolysis outcomes. FXIII-A Leu34 carrier status was associated with smaller thrombus burden, which is consistent with the in vitro described whole blood clot mass reducing effects of the allele, but the polymorphism had no effect on thrombolysis outcomes.István SzegediRita Orbán-KálmándiAttila NagyFerenc SarkadyNikolett VasasMáté SikLevente István LáncziErvin BerényiLászló OláhAlexandra CrișanLászló CsibaZsuzsa BagolyPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 7, p e0254253 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q István Szegedi Rita Orbán-Kálmándi Attila Nagy Ferenc Sarkady Nikolett Vasas Máté Sik Levente István Lánczi Ervin Berényi László Oláh Alexandra Crișan László Csiba Zsuzsa Bagoly Decreased clot burden is associated with factor XIII Val34Leu polymorphism and better functional outcomes in acute ischemic stroke patients treated with intravenous thrombolysis.
description	<h4>Background</h4>Intravenous thrombolysis using recombinant tissue plasminogen activator remains the mainstay treatment of acute ischemic stroke (AIS), although endovascular treatment is becoming standard of care in case of large vessel occlusions (LVO). To quantify the thrombus burden in LVO, a semiquantitative CT angiography (CTA) grading system, the clot burden score (CBS) can be used. Here we aimed to study the association between CBS and various hemostasis parameters, and to evaluate which parameters are major determinants of thrombolysis outcome.<h4>Methods</h4>In this single-centered prospective observational case-control study, 200 anterior circulation AIS patients receiving intravenous thrombolysis treatment without thrombectomy were enrolled: 100 AIS patients with LVO (CBS 0-9) and 100 age- and sex-matched AIS patients without LVO (CBS 10). Fibrinogen, α2-plasmin inhibitor, plasminogen, factor XIII and D-dimer were assessed from blood samples taken before and 24 h after thrombolysis, and FXIII-A Val34Leu was genotyped. CBS was calculated using admission CTA. Short-term outcomes were defined based on the change in NIHSS by day 7, long-term outcomes were assessed according to the modified Rankin scale at 3 months post-event.<h4>Results</h4>Poor outcomes were significantly more frequent in the CBS 0-9 group. Plasminogen activity on admission was significantly higher in the CBS 0-9 group. In a univariate analysis, significant protective effect of the Leu34 allele against developing larger clots (CBS 0-9) could be demonstrated (OR:0.519; 95%CI:0.298-0.922, p = 0.0227). Multivariate regression analysis revealed that CBS is an independent predictor of short- and long-term functional outcomes, while such effect of the studied hemostasis parameters could not be demonstrated.<h4>Conclusions</h4>CBS was found to be a significant independent predictor of thrombolysis outcomes. FXIII-A Leu34 carrier status was associated with smaller thrombus burden, which is consistent with the in vitro described whole blood clot mass reducing effects of the allele, but the polymorphism had no effect on thrombolysis outcomes.
format	article
author	István Szegedi Rita Orbán-Kálmándi Attila Nagy Ferenc Sarkady Nikolett Vasas Máté Sik Levente István Lánczi Ervin Berényi László Oláh Alexandra Crișan László Csiba Zsuzsa Bagoly
author_facet	István Szegedi Rita Orbán-Kálmándi Attila Nagy Ferenc Sarkady Nikolett Vasas Máté Sik Levente István Lánczi Ervin Berényi László Oláh Alexandra Crișan László Csiba Zsuzsa Bagoly
author_sort	István Szegedi
title	Decreased clot burden is associated with factor XIII Val34Leu polymorphism and better functional outcomes in acute ischemic stroke patients treated with intravenous thrombolysis.
title_short	Decreased clot burden is associated with factor XIII Val34Leu polymorphism and better functional outcomes in acute ischemic stroke patients treated with intravenous thrombolysis.
title_full	Decreased clot burden is associated with factor XIII Val34Leu polymorphism and better functional outcomes in acute ischemic stroke patients treated with intravenous thrombolysis.
title_fullStr	Decreased clot burden is associated with factor XIII Val34Leu polymorphism and better functional outcomes in acute ischemic stroke patients treated with intravenous thrombolysis.
title_full_unstemmed	Decreased clot burden is associated with factor XIII Val34Leu polymorphism and better functional outcomes in acute ischemic stroke patients treated with intravenous thrombolysis.
title_sort	decreased clot burden is associated with factor xiii val34leu polymorphism and better functional outcomes in acute ischemic stroke patients treated with intravenous thrombolysis.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/f9f2cb92308d4b51b52d72f1094f2e0f
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Decreased clot burden is associated with factor XIII Val34Leu polymorphism and better functional outcomes in acute ischemic stroke patients treated with intravenous thrombolysis.

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