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Characterization of ADAMTS13 and von Willebrand factor levels in septic and non-septic ICU patients

Sepsis is a life-threatening disease characterized by excessive host response to infection that can lead to activation of the coagulation system. Von Willebrand Factor (VWF) and ADAMTS13 are important regulators of hemostasis and their dysregulation during sepsis progression is not well understood....

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Autores principales: Singh, Kanwal, Kwong, Andrew C., Madarati, Hasam, Kunasekaran, Sharumathy, Sparring, Taylor, Fox-Robichaud, Alison E., Liaw, Patricia C., Kretz, Colin A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894828/
https://www.ncbi.nlm.nih.gov/pubmed/33606732
http://dx.doi.org/10.1371/journal.pone.0247017
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author Singh, Kanwal
Kwong, Andrew C.
Madarati, Hasam
Kunasekaran, Sharumathy
Sparring, Taylor
Fox-Robichaud, Alison E.
Liaw, Patricia C.
Kretz, Colin A.
author_facet Singh, Kanwal
Kwong, Andrew C.
Madarati, Hasam
Kunasekaran, Sharumathy
Sparring, Taylor
Fox-Robichaud, Alison E.
Liaw, Patricia C.
Kretz, Colin A.
author_sort Singh, Kanwal
collection PubMed
description Sepsis is a life-threatening disease characterized by excessive host response to infection that can lead to activation of the coagulation system. Von Willebrand Factor (VWF) and ADAMTS13 are important regulators of hemostasis and their dysregulation during sepsis progression is not well understood. Herein we characterize ADAMTS13 and VWF in septic and non-septic patients. ADAMTS13 activity, ADAMTS13 antigen, VWF antigen, myeloperoxidase, and protein C, were measured in plasma collected from 40 septic patients (20 non-survivors and 20 survivors) and 40 non-septic patients on the first and last day of their ICU stay. ADAMTS13 activity and ADAMTS13 antigen were reduced, whereas VWF antigen was elevated among septic patients compared to non-septic patients and healthy controls. Non-septic patients also exhibited elevated VWF antigen and reduced ADAMTS13 activity, but to a lesser extent than septic patients. Non-survivor septic patients exhibited the lowest levels of ADAMTS13 activity. ADAMTS13 activity:antigen ratio was similar across all patient cohorts suggesting that the specific activity of ADAMTS13 remains unchanged. Therefore, reduced ADAMTS13 function in circulation is likely due to a reduction in circulating levels. We suggest that massive release of VWF in response to inflammation consumes limited circulating ADAMTS13, resulting in the imbalance observed between VWF and ADAMTS13 among septic and to a lesser extent in non-septic ICU patients. Changes to ADAMTS13 did not correlate with myeloperoxidase or protein C levels. Reduced ADAMTS13 activity and antigen, and elevated VWF antigen observed among all patient cohorts on admission remained unchanged in survivors at ICU discharge. Prolonged reduction in ADAMTS13 activity and antigen in septic patients coincides with elevated levels of VWF. The persistent abnormalities in ADAMTS13 and VWF in sepsis patients discharged from the ICU may contribute to a sustained prothrombotic state.
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spelling pubmed-78948282021-03-01 Characterization of ADAMTS13 and von Willebrand factor levels in septic and non-septic ICU patients Singh, Kanwal Kwong, Andrew C. Madarati, Hasam Kunasekaran, Sharumathy Sparring, Taylor Fox-Robichaud, Alison E. Liaw, Patricia C. Kretz, Colin A. PLoS One Research Article Sepsis is a life-threatening disease characterized by excessive host response to infection that can lead to activation of the coagulation system. Von Willebrand Factor (VWF) and ADAMTS13 are important regulators of hemostasis and their dysregulation during sepsis progression is not well understood. Herein we characterize ADAMTS13 and VWF in septic and non-septic patients. ADAMTS13 activity, ADAMTS13 antigen, VWF antigen, myeloperoxidase, and protein C, were measured in plasma collected from 40 septic patients (20 non-survivors and 20 survivors) and 40 non-septic patients on the first and last day of their ICU stay. ADAMTS13 activity and ADAMTS13 antigen were reduced, whereas VWF antigen was elevated among septic patients compared to non-septic patients and healthy controls. Non-septic patients also exhibited elevated VWF antigen and reduced ADAMTS13 activity, but to a lesser extent than septic patients. Non-survivor septic patients exhibited the lowest levels of ADAMTS13 activity. ADAMTS13 activity:antigen ratio was similar across all patient cohorts suggesting that the specific activity of ADAMTS13 remains unchanged. Therefore, reduced ADAMTS13 function in circulation is likely due to a reduction in circulating levels. We suggest that massive release of VWF in response to inflammation consumes limited circulating ADAMTS13, resulting in the imbalance observed between VWF and ADAMTS13 among septic and to a lesser extent in non-septic ICU patients. Changes to ADAMTS13 did not correlate with myeloperoxidase or protein C levels. Reduced ADAMTS13 activity and antigen, and elevated VWF antigen observed among all patient cohorts on admission remained unchanged in survivors at ICU discharge. Prolonged reduction in ADAMTS13 activity and antigen in septic patients coincides with elevated levels of VWF. The persistent abnormalities in ADAMTS13 and VWF in sepsis patients discharged from the ICU may contribute to a sustained prothrombotic state. Public Library of Science 2021-02-19 /pmc/articles/PMC7894828/ /pubmed/33606732 http://dx.doi.org/10.1371/journal.pone.0247017 Text en © 2021 Singh 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
Singh, Kanwal
Kwong, Andrew C.
Madarati, Hasam
Kunasekaran, Sharumathy
Sparring, Taylor
Fox-Robichaud, Alison E.
Liaw, Patricia C.
Kretz, Colin A.
Characterization of ADAMTS13 and von Willebrand factor levels in septic and non-septic ICU patients
title Characterization of ADAMTS13 and von Willebrand factor levels in septic and non-septic ICU patients
title_full Characterization of ADAMTS13 and von Willebrand factor levels in septic and non-septic ICU patients
title_fullStr Characterization of ADAMTS13 and von Willebrand factor levels in septic and non-septic ICU patients
title_full_unstemmed Characterization of ADAMTS13 and von Willebrand factor levels in septic and non-septic ICU patients
title_short Characterization of ADAMTS13 and von Willebrand factor levels in septic and non-septic ICU patients
title_sort characterization of adamts13 and von willebrand factor levels in septic and non-septic icu patients
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894828/
https://www.ncbi.nlm.nih.gov/pubmed/33606732
http://dx.doi.org/10.1371/journal.pone.0247017
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