Discrepant fibrinolytic response in plasma and whole blood during experimental endotoxemia in healthy volunteers
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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.
In: PLoS ONE, Vol. 8, No. 3, e59368, 2013.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Discrepant fibrinolytic response in plasma and whole blood during experimental endotoxemia in healthy volunteers
AU - Ostrowski, Sisse R
AU - Berg, Ronan M G
AU - Windeløv, Nis A
AU - Meyer, Martin A S
AU - Plovsing, Ronni R
AU - Møller, Kirsten
AU - Johansson, Pär I
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - Blood Coagulation
KW - Blood Platelets/metabolism
KW - Blood Pressure
KW - Calcitonin/blood
KW - Calcitonin Gene-Related Peptide
KW - Endotoxemia/blood
KW - Erythrocytes/metabolism
KW - Fibrinogen/metabolism
KW - Humans
KW - Lipopolysaccharides
KW - Male
KW - Partial Thromboplastin Time
KW - Platelet Aggregation
KW - Prospective Studies
KW - Protein Precursors/blood
KW - Thrombelastography
KW - Tissue Plasminogen Activator/blood
KW - Whole Blood Coagulation Time
KW - Young Adult
U2 - 10.1371/journal.pone.0059368
DO - 10.1371/journal.pone.0059368
M3 - Journal article
C2 - 23555024
VL - 8
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 3
M1 - e59368
ER -
ID: 236993546