Cargando…
Discrepant Fibrinolytic Response in Plasma and Whole Blood during Experimental Endotoxemia in Healthy Volunteers
BACKGROUND: Sepsis induces early activation of coagulation and fibrinolysis followed by late fibrinolytic shutdown and progressive endothelial damage. The aim of the present study was to investigate and compare the functional hemostatic response in whole blood and plasma during experimental human en...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3598702/ https://www.ncbi.nlm.nih.gov/pubmed/23555024 http://dx.doi.org/10.1371/journal.pone.0059368 |
_version_ | 1782262803926614016 |
---|---|
author | Ostrowski, Sisse R. Berg, Ronan M. G. Windeløv, Nis A. Meyer, Martin A. S. Plovsing, Ronni R. Møller, Kirsten Johansson, Pär I. |
author_facet | Ostrowski, Sisse R. Berg, Ronan M. G. Windeløv, Nis A. Meyer, Martin A. S. Plovsing, Ronni R. Møller, Kirsten Johansson, Pär I. |
author_sort | Ostrowski, Sisse R. |
collection | PubMed |
description | BACKGROUND: Sepsis induces early activation of coagulation and fibrinolysis followed by late fibrinolytic shutdown and progressive endothelial damage. The aim of the present study was to investigate and compare the functional hemostatic response in whole blood and plasma during experimental human endotoxemia by the platelet function analyzer, Multiplate and by standard and modified thrombelastography (TEG). METHODS: Prospective physiologic study of nine healthy male volunteers undergoing endotoxemia by means of a 4-hour infusion of E. coli lipopolysaccharide (LPS, 0.5 ng/kg/hour), with blood sampled at baseline and at 4 h and 6 h. Physiological and standard biochemical data and coagulation tests, TEG (whole blood: TEG, heparinase-TEG, Functional Fibrinogen; plasma: TEG±tissue-type plasminogen activator (tPA)) and Multiplate (TRAPtest, ADPtest, ASPItest, COLtest) were recorded. Mixed models with Tukey post hoc tests and correlations were applied. RESULTS: Endotoxemia induced acute SIRS with increased HR, temperature, WBC, CRP and procalcitonin and decreased blood pressure. It also induced a hemostatic response with platelet consumption and reduced APTT while INR increased (all p<0.05). Platelet aggregation decreased (all tests, p<0.05), whereas TEG whole blood clot firmness increased (G, p = 0.05). Furthermore, during endotoxemia (4 h), whole blood fibrinolysis increased (clot lysis time (CLT), p<0.001) and Functional Fibrinogen clot strength decreased (p = 0.049). After endotoxemia (6 h), whole blood fibrinolysis was reduced (CLT, p<0.05). In contrast to findings in whole blood, the plasma fibrin clot became progressively more resistant towards tPA-induced fibrinolysis at both 4 h and 6 h (p<0.001). CONCLUSIONS: Endotoxemia induced a hemostatic response with reduced primary but enhanced secondary hemostasis, enhanced early fibrinolysis and fibrinogen consumption followed by downregulation of fibrinolysis, with a discrepant fibrinolytic response in plasma and whole blood. The finding that blood cells are critically involved in the vasculo-fibrinolytic response to acute inflammation is important given that disturbances in the vascular system contribute significantly to morbidity and mortality in critically ill patients. |
format | Online Article Text |
id | pubmed-3598702 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-35987022013-04-02 Discrepant Fibrinolytic Response in Plasma and Whole Blood during Experimental Endotoxemia in Healthy Volunteers Ostrowski, Sisse R. Berg, Ronan M. G. Windeløv, Nis A. Meyer, Martin A. S. Plovsing, Ronni R. Møller, Kirsten Johansson, Pär I. PLoS One Research Article BACKGROUND: Sepsis induces early activation of coagulation and fibrinolysis followed by late fibrinolytic shutdown and progressive endothelial damage. The aim of the present study was to investigate and compare the functional hemostatic response in whole blood and plasma during experimental human endotoxemia by the platelet function analyzer, Multiplate and by standard and modified thrombelastography (TEG). METHODS: Prospective physiologic study of nine healthy male volunteers undergoing endotoxemia by means of a 4-hour infusion of E. coli lipopolysaccharide (LPS, 0.5 ng/kg/hour), with blood sampled at baseline and at 4 h and 6 h. Physiological and standard biochemical data and coagulation tests, TEG (whole blood: TEG, heparinase-TEG, Functional Fibrinogen; plasma: TEG±tissue-type plasminogen activator (tPA)) and Multiplate (TRAPtest, ADPtest, ASPItest, COLtest) were recorded. Mixed models with Tukey post hoc tests and correlations were applied. RESULTS: Endotoxemia induced acute SIRS with increased HR, temperature, WBC, CRP and procalcitonin and decreased blood pressure. It also induced a hemostatic response with platelet consumption and reduced APTT while INR increased (all p<0.05). Platelet aggregation decreased (all tests, p<0.05), whereas TEG whole blood clot firmness increased (G, p = 0.05). Furthermore, during endotoxemia (4 h), whole blood fibrinolysis increased (clot lysis time (CLT), p<0.001) and Functional Fibrinogen clot strength decreased (p = 0.049). After endotoxemia (6 h), whole blood fibrinolysis was reduced (CLT, p<0.05). In contrast to findings in whole blood, the plasma fibrin clot became progressively more resistant towards tPA-induced fibrinolysis at both 4 h and 6 h (p<0.001). CONCLUSIONS: Endotoxemia induced a hemostatic response with reduced primary but enhanced secondary hemostasis, enhanced early fibrinolysis and fibrinogen consumption followed by downregulation of fibrinolysis, with a discrepant fibrinolytic response in plasma and whole blood. The finding that blood cells are critically involved in the vasculo-fibrinolytic response to acute inflammation is important given that disturbances in the vascular system contribute significantly to morbidity and mortality in critically ill patients. Public Library of Science 2013-03-15 /pmc/articles/PMC3598702/ /pubmed/23555024 http://dx.doi.org/10.1371/journal.pone.0059368 Text en © 2013 Ostrowski 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Ostrowski, Sisse R. Berg, Ronan M. G. Windeløv, Nis A. Meyer, Martin A. S. Plovsing, Ronni R. Møller, Kirsten Johansson, Pär I. Discrepant Fibrinolytic Response in Plasma and Whole Blood during Experimental Endotoxemia in Healthy Volunteers |
title | Discrepant Fibrinolytic Response in Plasma and Whole Blood during Experimental Endotoxemia in Healthy Volunteers |
title_full | Discrepant Fibrinolytic Response in Plasma and Whole Blood during Experimental Endotoxemia in Healthy Volunteers |
title_fullStr | Discrepant Fibrinolytic Response in Plasma and Whole Blood during Experimental Endotoxemia in Healthy Volunteers |
title_full_unstemmed | Discrepant Fibrinolytic Response in Plasma and Whole Blood during Experimental Endotoxemia in Healthy Volunteers |
title_short | Discrepant Fibrinolytic Response in Plasma and Whole Blood during Experimental Endotoxemia in Healthy Volunteers |
title_sort | discrepant fibrinolytic response in plasma and whole blood during experimental endotoxemia in healthy volunteers |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3598702/ https://www.ncbi.nlm.nih.gov/pubmed/23555024 http://dx.doi.org/10.1371/journal.pone.0059368 |
work_keys_str_mv | AT ostrowskisisser discrepantfibrinolyticresponseinplasmaandwholebloodduringexperimentalendotoxemiainhealthyvolunteers AT bergronanmg discrepantfibrinolyticresponseinplasmaandwholebloodduringexperimentalendotoxemiainhealthyvolunteers AT windeløvnisa discrepantfibrinolyticresponseinplasmaandwholebloodduringexperimentalendotoxemiainhealthyvolunteers AT meyermartinas discrepantfibrinolyticresponseinplasmaandwholebloodduringexperimentalendotoxemiainhealthyvolunteers AT plovsingronnir discrepantfibrinolyticresponseinplasmaandwholebloodduringexperimentalendotoxemiainhealthyvolunteers AT møllerkirsten discrepantfibrinolyticresponseinplasmaandwholebloodduringexperimentalendotoxemiainhealthyvolunteers AT johanssonpari discrepantfibrinolyticresponseinplasmaandwholebloodduringexperimentalendotoxemiainhealthyvolunteers |