A modified in vitro clot lysis assay predicts outcomes and safety in acute ischemic stroke patients undergoing intravenous thrombolysis

Abstract The outcome of intravenous thrombolysis using recombinant tissue plasminogen activator (rt-PA) is only favorable in ≈ 40% of acute ischemic stroke (AIS) patients. Moreover, in ≈ 6–8% of cases, intracerebral hemorrhage (ICH) develops. We tested whether a modification of clot lysis assay (CLA...

Full description

Bibliographic Details
Main Authors: Rita Orbán-Kálmándi, István Szegedi, Ferenc Sarkady, István Fekete, Klára Fekete, Nikolett Vasas, Ervin Berényi, László Csiba, Zsuzsa Bagoly
Format: Article
Language:English
Published: Nature Publishing Group 2021-06-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-92041-1
id doaj-af99f94ee0064776ab13f80afb582255
record_format Article
spelling doaj-af99f94ee0064776ab13f80afb5822552021-06-20T11:33:06ZengNature Publishing GroupScientific Reports2045-23222021-06-0111111410.1038/s41598-021-92041-1A modified in vitro clot lysis assay predicts outcomes and safety in acute ischemic stroke patients undergoing intravenous thrombolysisRita Orbán-Kálmándi0István Szegedi1Ferenc Sarkady2István Fekete3Klára Fekete4Nikolett Vasas5Ervin Berényi6László Csiba7Zsuzsa Bagoly8Division of Clinical Laboratory Sciences, Department of Laboratory Medicine, Faculty of Medicine, Kálmán Laki Doctoral School, University of DebrecenDepartment of Neurology, Faculty of Medicine, University of DebrecenDivision of Clinical Laboratory Sciences, Department of Laboratory Medicine, Faculty of Medicine, Kálmán Laki Doctoral School, University of DebrecenDepartment of Neurology, Faculty of Medicine, University of DebrecenDepartment of Neurology, Faculty of Medicine, University of DebrecenDepartment of Radiology, Faculty of Medicine, University of DebrecenDepartment of Radiology, Faculty of Medicine, University of DebrecenDepartment of Neurology, Faculty of Medicine, University of DebrecenDivision of Clinical Laboratory Sciences, Department of Laboratory Medicine, Faculty of Medicine, Kálmán Laki Doctoral School, University of DebrecenAbstract The outcome of intravenous thrombolysis using recombinant tissue plasminogen activator (rt-PA) is only favorable in ≈ 40% of acute ischemic stroke (AIS) patients. Moreover, in ≈ 6–8% of cases, intracerebral hemorrhage (ICH) develops. We tested whether a modification of clot lysis assay (CLA), might predict therapy outcomes and safety. In this prospective observational study, blood samples of 231 AIS patients, all receiving intravenous rt-PA, were taken before thrombolysis. Cell-free DNA (cfDNA), CLA and CLA supplemented with cfDNA and histones (mCLA) were determined from the blood samples. Stroke severity was determined by NIHSS on admission. ICH was classified according to ECASSII. Short- and long-term outcomes were defined at 7 and 90 days post-event according to ΔNIHSS and by the modified Rankin Scale, respectively. Stroke severity demonstrated a step-wise positive association with cfDNA levels, while a negative association was found with the time to reach 50% lysis (50%CLT) parameter of CLA and mCLA. ROC analysis showed improved diagnostic performance of the mCLA. Logistic regression analysis proved that 50%CLT is a predictor of short-term therapy failure, while the AUC parameter predicts ICH occurrence. A modified CLA, supplemented with cfDNA and histones, might be a promising tool to predict short-term AIS outcomes and post-lysis ICH.https://doi.org/10.1038/s41598-021-92041-1
collection DOAJ
language English
format Article
sources DOAJ
author Rita Orbán-Kálmándi
István Szegedi
Ferenc Sarkady
István Fekete
Klára Fekete
Nikolett Vasas
Ervin Berényi
László Csiba
Zsuzsa Bagoly
spellingShingle Rita Orbán-Kálmándi
István Szegedi
Ferenc Sarkady
István Fekete
Klára Fekete
Nikolett Vasas
Ervin Berényi
László Csiba
Zsuzsa Bagoly
A modified in vitro clot lysis assay predicts outcomes and safety in acute ischemic stroke patients undergoing intravenous thrombolysis
Scientific Reports
author_facet Rita Orbán-Kálmándi
István Szegedi
Ferenc Sarkady
István Fekete
Klára Fekete
Nikolett Vasas
Ervin Berényi
László Csiba
Zsuzsa Bagoly
author_sort Rita Orbán-Kálmándi
title A modified in vitro clot lysis assay predicts outcomes and safety in acute ischemic stroke patients undergoing intravenous thrombolysis
title_short A modified in vitro clot lysis assay predicts outcomes and safety in acute ischemic stroke patients undergoing intravenous thrombolysis
title_full A modified in vitro clot lysis assay predicts outcomes and safety in acute ischemic stroke patients undergoing intravenous thrombolysis
title_fullStr A modified in vitro clot lysis assay predicts outcomes and safety in acute ischemic stroke patients undergoing intravenous thrombolysis
title_full_unstemmed A modified in vitro clot lysis assay predicts outcomes and safety in acute ischemic stroke patients undergoing intravenous thrombolysis
title_sort modified in vitro clot lysis assay predicts outcomes and safety in acute ischemic stroke patients undergoing intravenous thrombolysis
publisher Nature Publishing Group
series Scientific Reports
issn 2045-2322
publishDate 2021-06-01
description Abstract The outcome of intravenous thrombolysis using recombinant tissue plasminogen activator (rt-PA) is only favorable in ≈ 40% of acute ischemic stroke (AIS) patients. Moreover, in ≈ 6–8% of cases, intracerebral hemorrhage (ICH) develops. We tested whether a modification of clot lysis assay (CLA), might predict therapy outcomes and safety. In this prospective observational study, blood samples of 231 AIS patients, all receiving intravenous rt-PA, were taken before thrombolysis. Cell-free DNA (cfDNA), CLA and CLA supplemented with cfDNA and histones (mCLA) were determined from the blood samples. Stroke severity was determined by NIHSS on admission. ICH was classified according to ECASSII. Short- and long-term outcomes were defined at 7 and 90 days post-event according to ΔNIHSS and by the modified Rankin Scale, respectively. Stroke severity demonstrated a step-wise positive association with cfDNA levels, while a negative association was found with the time to reach 50% lysis (50%CLT) parameter of CLA and mCLA. ROC analysis showed improved diagnostic performance of the mCLA. Logistic regression analysis proved that 50%CLT is a predictor of short-term therapy failure, while the AUC parameter predicts ICH occurrence. A modified CLA, supplemented with cfDNA and histones, might be a promising tool to predict short-term AIS outcomes and post-lysis ICH.
url https://doi.org/10.1038/s41598-021-92041-1
work_keys_str_mv AT ritaorbankalmandi amodifiedinvitroclotlysisassaypredictsoutcomesandsafetyinacuteischemicstrokepatientsundergoingintravenousthrombolysis
AT istvanszegedi amodifiedinvitroclotlysisassaypredictsoutcomesandsafetyinacuteischemicstrokepatientsundergoingintravenousthrombolysis
AT ferencsarkady amodifiedinvitroclotlysisassaypredictsoutcomesandsafetyinacuteischemicstrokepatientsundergoingintravenousthrombolysis
AT istvanfekete amodifiedinvitroclotlysisassaypredictsoutcomesandsafetyinacuteischemicstrokepatientsundergoingintravenousthrombolysis
AT klarafekete amodifiedinvitroclotlysisassaypredictsoutcomesandsafetyinacuteischemicstrokepatientsundergoingintravenousthrombolysis
AT nikolettvasas amodifiedinvitroclotlysisassaypredictsoutcomesandsafetyinacuteischemicstrokepatientsundergoingintravenousthrombolysis
AT ervinberenyi amodifiedinvitroclotlysisassaypredictsoutcomesandsafetyinacuteischemicstrokepatientsundergoingintravenousthrombolysis
AT laszlocsiba amodifiedinvitroclotlysisassaypredictsoutcomesandsafetyinacuteischemicstrokepatientsundergoingintravenousthrombolysis
AT zsuzsabagoly amodifiedinvitroclotlysisassaypredictsoutcomesandsafetyinacuteischemicstrokepatientsundergoingintravenousthrombolysis
AT ritaorbankalmandi modifiedinvitroclotlysisassaypredictsoutcomesandsafetyinacuteischemicstrokepatientsundergoingintravenousthrombolysis
AT istvanszegedi modifiedinvitroclotlysisassaypredictsoutcomesandsafetyinacuteischemicstrokepatientsundergoingintravenousthrombolysis
AT ferencsarkady modifiedinvitroclotlysisassaypredictsoutcomesandsafetyinacuteischemicstrokepatientsundergoingintravenousthrombolysis
AT istvanfekete modifiedinvitroclotlysisassaypredictsoutcomesandsafetyinacuteischemicstrokepatientsundergoingintravenousthrombolysis
AT klarafekete modifiedinvitroclotlysisassaypredictsoutcomesandsafetyinacuteischemicstrokepatientsundergoingintravenousthrombolysis
AT nikolettvasas modifiedinvitroclotlysisassaypredictsoutcomesandsafetyinacuteischemicstrokepatientsundergoingintravenousthrombolysis
AT ervinberenyi modifiedinvitroclotlysisassaypredictsoutcomesandsafetyinacuteischemicstrokepatientsundergoingintravenousthrombolysis
AT laszlocsiba modifiedinvitroclotlysisassaypredictsoutcomesandsafetyinacuteischemicstrokepatientsundergoingintravenousthrombolysis
AT zsuzsabagoly modifiedinvitroclotlysisassaypredictsoutcomesandsafetyinacuteischemicstrokepatientsundergoingintravenousthrombolysis
_version_ 1721370022049218560