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High CSF thrombin concentration and activity is associated with an unfavorable outcome in patients with intracerebral hemorrhage

BACKGROUND: The cerebral thrombin system is activated in the early stage after intracerebral hemorrhage (ICH). Expression of thrombin leads to concentration dependent secondary neuronal damage and detrimental neurological outcome. In this study we aimed to investigate the impact of thrombin concentr...

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Autores principales: Krenzlin, Harald, Frenz, Christina, Schmitt, Jan, Masomi-Bornwasser, Julia, Wesp, Dominik, Kalasauskas, Darius, Kerz, Thomas, Lotz, Johannes, Alessandri, Beat, Ringel, Florian, Keric, Naureen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657554/
https://www.ncbi.nlm.nih.gov/pubmed/33175864
http://dx.doi.org/10.1371/journal.pone.0241565
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author Krenzlin, Harald
Frenz, Christina
Schmitt, Jan
Masomi-Bornwasser, Julia
Wesp, Dominik
Kalasauskas, Darius
Kerz, Thomas
Lotz, Johannes
Alessandri, Beat
Ringel, Florian
Keric, Naureen
author_facet Krenzlin, Harald
Frenz, Christina
Schmitt, Jan
Masomi-Bornwasser, Julia
Wesp, Dominik
Kalasauskas, Darius
Kerz, Thomas
Lotz, Johannes
Alessandri, Beat
Ringel, Florian
Keric, Naureen
author_sort Krenzlin, Harald
collection PubMed
description BACKGROUND: The cerebral thrombin system is activated in the early stage after intracerebral hemorrhage (ICH). Expression of thrombin leads to concentration dependent secondary neuronal damage and detrimental neurological outcome. In this study we aimed to investigate the impact of thrombin concentration and activity in the cerebrospinal fluid (CSF) of patients with ICH on clinical outcome. METHODS: Patients presenting with space-occupying lobar supratentorial hemorrhage requiring extra-ventricular drainage (EVD) were included in our study. The CSF levels of thrombin, its precursor prothrombin and the Thrombin-Antithrombin complex (TAT) were measured using enzyme linked immune sorbent assays (ELISA). The oxidative stress marker Superoxide dismutase (SOD) was assessed in CSF. Initial clot size and intraventricular hemorrhage (IVH) volume was calculated based on by computerized tomography (CT) upon admission to our hospital. Demographic data, clinical status at admission and neurological outcome were assessed using the modified Rankin Scale (mRS) at 6-weeks and 6-month after ICH. RESULTS: Twenty-two consecutive patients (9 females, 11 males) with supratentorial hemorrhage were included in this study. CSF concentrations of prothrombin (p < 0.005), thrombin (p = 0.005) and TAT (p = 0.046) were statistical significantly different in patients with ICH compared to non-hemorrhagic CSF samples. CSF concentrations of thrombin 24h after ICH correlated with the mRS index after 6 weeks (r(2) = 0.73; < 0.005) and 6 months (r(2) = 0.63; < 0.005) after discharge from hospital. Thrombin activity, measured via TAT as surrogate parameter of coagulation, likewise correlated with the mRS at 6 weeks (r(2) = 0.54; < 0.01) and 6 months (r(2) = 0.66; < 0.04). High thrombin concentrations coincide with higher SOD levels 24h after ICH (p = 0.01). CONCLUSION: In this study we found that initial thrombin concentration and activity in CSF of ICH patients did not correlate with ICH and IVH volume but are associated with a poorer functional neurological outcome. These findings support mounting evidence of the role of thrombin as a contributor to secondary injury formation after ICH.
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spelling pubmed-76575542020-11-18 High CSF thrombin concentration and activity is associated with an unfavorable outcome in patients with intracerebral hemorrhage Krenzlin, Harald Frenz, Christina Schmitt, Jan Masomi-Bornwasser, Julia Wesp, Dominik Kalasauskas, Darius Kerz, Thomas Lotz, Johannes Alessandri, Beat Ringel, Florian Keric, Naureen PLoS One Research Article BACKGROUND: The cerebral thrombin system is activated in the early stage after intracerebral hemorrhage (ICH). Expression of thrombin leads to concentration dependent secondary neuronal damage and detrimental neurological outcome. In this study we aimed to investigate the impact of thrombin concentration and activity in the cerebrospinal fluid (CSF) of patients with ICH on clinical outcome. METHODS: Patients presenting with space-occupying lobar supratentorial hemorrhage requiring extra-ventricular drainage (EVD) were included in our study. The CSF levels of thrombin, its precursor prothrombin and the Thrombin-Antithrombin complex (TAT) were measured using enzyme linked immune sorbent assays (ELISA). The oxidative stress marker Superoxide dismutase (SOD) was assessed in CSF. Initial clot size and intraventricular hemorrhage (IVH) volume was calculated based on by computerized tomography (CT) upon admission to our hospital. Demographic data, clinical status at admission and neurological outcome were assessed using the modified Rankin Scale (mRS) at 6-weeks and 6-month after ICH. RESULTS: Twenty-two consecutive patients (9 females, 11 males) with supratentorial hemorrhage were included in this study. CSF concentrations of prothrombin (p < 0.005), thrombin (p = 0.005) and TAT (p = 0.046) were statistical significantly different in patients with ICH compared to non-hemorrhagic CSF samples. CSF concentrations of thrombin 24h after ICH correlated with the mRS index after 6 weeks (r(2) = 0.73; < 0.005) and 6 months (r(2) = 0.63; < 0.005) after discharge from hospital. Thrombin activity, measured via TAT as surrogate parameter of coagulation, likewise correlated with the mRS at 6 weeks (r(2) = 0.54; < 0.01) and 6 months (r(2) = 0.66; < 0.04). High thrombin concentrations coincide with higher SOD levels 24h after ICH (p = 0.01). CONCLUSION: In this study we found that initial thrombin concentration and activity in CSF of ICH patients did not correlate with ICH and IVH volume but are associated with a poorer functional neurological outcome. These findings support mounting evidence of the role of thrombin as a contributor to secondary injury formation after ICH. Public Library of Science 2020-11-11 /pmc/articles/PMC7657554/ /pubmed/33175864 http://dx.doi.org/10.1371/journal.pone.0241565 Text en © 2020 Krenzlin et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Krenzlin, Harald
Frenz, Christina
Schmitt, Jan
Masomi-Bornwasser, Julia
Wesp, Dominik
Kalasauskas, Darius
Kerz, Thomas
Lotz, Johannes
Alessandri, Beat
Ringel, Florian
Keric, Naureen
High CSF thrombin concentration and activity is associated with an unfavorable outcome in patients with intracerebral hemorrhage
title High CSF thrombin concentration and activity is associated with an unfavorable outcome in patients with intracerebral hemorrhage
title_full High CSF thrombin concentration and activity is associated with an unfavorable outcome in patients with intracerebral hemorrhage
title_fullStr High CSF thrombin concentration and activity is associated with an unfavorable outcome in patients with intracerebral hemorrhage
title_full_unstemmed High CSF thrombin concentration and activity is associated with an unfavorable outcome in patients with intracerebral hemorrhage
title_short High CSF thrombin concentration and activity is associated with an unfavorable outcome in patients with intracerebral hemorrhage
title_sort high csf thrombin concentration and activity is associated with an unfavorable outcome in patients with intracerebral hemorrhage
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657554/
https://www.ncbi.nlm.nih.gov/pubmed/33175864
http://dx.doi.org/10.1371/journal.pone.0241565
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