Endothelial Injury and Glycocalyx Degradation in Critically Ill Coronavirus Disease 2019 Patients: Implications for Microvascular Platelet Aggregation
Objectives:. Coronavirus disease 2019 is caused by the novel severe acute respiratory syndrome coronavirus 2 virus. Patients admitted to the ICU suffer from microvascular thrombosis, which may contribute to mortality. Our aim was to profile plasma thrombotic factors and endothelial injury markers in...
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Wolters Kluwer
2020
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oai:doaj.org-article:b201f1567225428ab5d1671023780bbd2021-11-25T07:52:08ZEndothelial Injury and Glycocalyx Degradation in Critically Ill Coronavirus Disease 2019 Patients: Implications for Microvascular Platelet Aggregation2639-802810.1097/CCE.0000000000000194https://doaj.org/article/b201f1567225428ab5d1671023780bbd2020-09-01T00:00:00Zhttp://journals.lww.com/10.1097/CCE.0000000000000194https://doaj.org/toc/2639-8028Objectives:. Coronavirus disease 2019 is caused by the novel severe acute respiratory syndrome coronavirus 2 virus. Patients admitted to the ICU suffer from microvascular thrombosis, which may contribute to mortality. Our aim was to profile plasma thrombotic factors and endothelial injury markers in critically ill coronavirus disease 2019 ICU patients to help understand their thrombotic mechanisms. Design:. Daily blood coagulation and thrombotic factor profiling with immunoassays and in vitro experiments on human pulmonary microvascular endothelial cells. Setting:. Tertiary care ICU and academic laboratory. Subjects:. All patients admitted to the ICU suspected of being infected with severe acute respiratory syndrome coronavirus 2, using standardized hospital screening methodologies, had daily blood samples collected until testing was confirmed coronavirus disease 2019 negative on either ICU day 3 or ICU day 7 if the patient was coronavirus disease 2019 positive. Interventions:. None. Measurement and Main Results:. Age- and sex-matched healthy control subjects and ICU patients that were either coronavirus disease 2019 positive or coronavirus disease 2019 negative were enrolled. Cohorts were well balanced with the exception that coronavirus disease 2019 positive patients were more likely than coronavirus disease 2019 negative patients to suffer bilateral pneumonia. Mortality rate for coronavirus disease 2019 positive ICU patients was 40%. Compared with healthy control subjects, coronavirus disease 2019 positive patients had higher plasma von Willebrand factor (p < 0.001) and glycocalyx-degradation products (chondroitin sulfate and syndecan-1; p < 0.01). When compared with coronavirus disease 2019 negative patients, coronavirus disease 2019 positive patients had persistently higher soluble P-selectin, hyaluronic acid, and syndecan-1 (p < 0.05), particularly on ICU day 3 and thereafter. Thrombosis profiling on ICU days 1–3 predicted coronavirus disease 2019 status with 85% accuracy and patient mortality with 86% accuracy. Surface hyaluronic acid removal from human pulmonary microvascular endothelial cells with hyaluronidase treatment resulted in depressed nitric oxide, an instigating mechanism for platelet adhesion to the microvascular endothelium. Conclusions:. Thrombosis profiling identified endothelial activation and glycocalyx degradation in coronavirus disease 2019 positive patients. Our data suggest that medications to protect and/or restore the endothelial glycocalyx, as well as platelet inhibitors, should be considered for further study.Douglas D. Fraser, MD, PhDEric K. Patterson, PhDMarat Slessarev, MD, MScSean E. Gill, PhDClaudio Martin, MD, MScMark Daley, PhDMichael R. Miller, PhDMaitray A. Patel, BScClaudia C. dos Santos, MD, MScKaren J. Bosma, MDDavid B. O’Gorman, PhDGediminas Cepinskas, DVM, PhDon behalf of the Lawson COVID19 Study TeamRobert ArntfieldIan BallGordon BarkwellTracey BentallKaren BosmaSaoirse CameronEileen CampbellDavid CarterCarolina Gillio-MeinaRobert HegeleNatalya OdoardiRam SinghKelly SummersSue TereschynWolters KluwerarticleMedical emergencies. Critical care. Intensive care. First aidRC86-88.9ENCritical Care Explorations, Vol 2, Iss 9, p e0194 (2020) |
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DOAJ |
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DOAJ |
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EN |
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Medical emergencies. Critical care. Intensive care. First aid RC86-88.9 |
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Medical emergencies. Critical care. Intensive care. First aid RC86-88.9 Douglas D. Fraser, MD, PhD Eric K. Patterson, PhD Marat Slessarev, MD, MSc Sean E. Gill, PhD Claudio Martin, MD, MSc Mark Daley, PhD Michael R. Miller, PhD Maitray A. Patel, BSc Claudia C. dos Santos, MD, MSc Karen J. Bosma, MD David B. O’Gorman, PhD Gediminas Cepinskas, DVM, PhD on behalf of the Lawson COVID19 Study Team Robert Arntfield Ian Ball Gordon Barkwell Tracey Bentall Karen Bosma Saoirse Cameron Eileen Campbell David Carter Carolina Gillio-Meina Robert Hegele Natalya Odoardi Ram Singh Kelly Summers Sue Tereschyn Endothelial Injury and Glycocalyx Degradation in Critically Ill Coronavirus Disease 2019 Patients: Implications for Microvascular Platelet Aggregation |
| description |
Objectives:. Coronavirus disease 2019 is caused by the novel severe acute respiratory syndrome coronavirus 2 virus. Patients admitted to the ICU suffer from microvascular thrombosis, which may contribute to mortality. Our aim was to profile plasma thrombotic factors and endothelial injury markers in critically ill coronavirus disease 2019 ICU patients to help understand their thrombotic mechanisms.
Design:. Daily blood coagulation and thrombotic factor profiling with immunoassays and in vitro experiments on human pulmonary microvascular endothelial cells.
Setting:. Tertiary care ICU and academic laboratory.
Subjects:. All patients admitted to the ICU suspected of being infected with severe acute respiratory syndrome coronavirus 2, using standardized hospital screening methodologies, had daily blood samples collected until testing was confirmed coronavirus disease 2019 negative on either ICU day 3 or ICU day 7 if the patient was coronavirus disease 2019 positive.
Interventions:. None.
Measurement and Main Results:. Age- and sex-matched healthy control subjects and ICU patients that were either coronavirus disease 2019 positive or coronavirus disease 2019 negative were enrolled. Cohorts were well balanced with the exception that coronavirus disease 2019 positive patients were more likely than coronavirus disease 2019 negative patients to suffer bilateral pneumonia. Mortality rate for coronavirus disease 2019 positive ICU patients was 40%. Compared with healthy control subjects, coronavirus disease 2019 positive patients had higher plasma von Willebrand factor (p < 0.001) and glycocalyx-degradation products (chondroitin sulfate and syndecan-1; p < 0.01). When compared with coronavirus disease 2019 negative patients, coronavirus disease 2019 positive patients had persistently higher soluble P-selectin, hyaluronic acid, and syndecan-1 (p < 0.05), particularly on ICU day 3 and thereafter. Thrombosis profiling on ICU days 1–3 predicted coronavirus disease 2019 status with 85% accuracy and patient mortality with 86% accuracy. Surface hyaluronic acid removal from human pulmonary microvascular endothelial cells with hyaluronidase treatment resulted in depressed nitric oxide, an instigating mechanism for platelet adhesion to the microvascular endothelium.
Conclusions:. Thrombosis profiling identified endothelial activation and glycocalyx degradation in coronavirus disease 2019 positive patients. Our data suggest that medications to protect and/or restore the endothelial glycocalyx, as well as platelet inhibitors, should be considered for further study. |
| format |
article |
| author |
Douglas D. Fraser, MD, PhD Eric K. Patterson, PhD Marat Slessarev, MD, MSc Sean E. Gill, PhD Claudio Martin, MD, MSc Mark Daley, PhD Michael R. Miller, PhD Maitray A. Patel, BSc Claudia C. dos Santos, MD, MSc Karen J. Bosma, MD David B. O’Gorman, PhD Gediminas Cepinskas, DVM, PhD on behalf of the Lawson COVID19 Study Team Robert Arntfield Ian Ball Gordon Barkwell Tracey Bentall Karen Bosma Saoirse Cameron Eileen Campbell David Carter Carolina Gillio-Meina Robert Hegele Natalya Odoardi Ram Singh Kelly Summers Sue Tereschyn |
| author_facet |
Douglas D. Fraser, MD, PhD Eric K. Patterson, PhD Marat Slessarev, MD, MSc Sean E. Gill, PhD Claudio Martin, MD, MSc Mark Daley, PhD Michael R. Miller, PhD Maitray A. Patel, BSc Claudia C. dos Santos, MD, MSc Karen J. Bosma, MD David B. O’Gorman, PhD Gediminas Cepinskas, DVM, PhD on behalf of the Lawson COVID19 Study Team Robert Arntfield Ian Ball Gordon Barkwell Tracey Bentall Karen Bosma Saoirse Cameron Eileen Campbell David Carter Carolina Gillio-Meina Robert Hegele Natalya Odoardi Ram Singh Kelly Summers Sue Tereschyn |
| author_sort |
Douglas D. Fraser, MD, PhD |
| title |
Endothelial Injury and Glycocalyx Degradation in Critically Ill Coronavirus Disease 2019 Patients: Implications for Microvascular Platelet Aggregation |
| title_short |
Endothelial Injury and Glycocalyx Degradation in Critically Ill Coronavirus Disease 2019 Patients: Implications for Microvascular Platelet Aggregation |
| title_full |
Endothelial Injury and Glycocalyx Degradation in Critically Ill Coronavirus Disease 2019 Patients: Implications for Microvascular Platelet Aggregation |
| title_fullStr |
Endothelial Injury and Glycocalyx Degradation in Critically Ill Coronavirus Disease 2019 Patients: Implications for Microvascular Platelet Aggregation |
| title_full_unstemmed |
Endothelial Injury and Glycocalyx Degradation in Critically Ill Coronavirus Disease 2019 Patients: Implications for Microvascular Platelet Aggregation |
| title_sort |
endothelial injury and glycocalyx degradation in critically ill coronavirus disease 2019 patients: implications for microvascular platelet aggregation |
| publisher |
Wolters Kluwer |
| publishDate |
2020 |
| url |
https://doaj.org/article/b201f1567225428ab5d1671023780bbd |
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