Quantification of fibrinolysis using velocity curves measured with thromboelastometry in children with congenital heart disease

David Faraoni, Philippe Van Der Linden, Anne Sophie Ducloy-Bouthors, Susan M. Goobie, James A. DiNardo, Vance G Nielsen

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Abstract

BACKGROUND: In this pilot study, we hypothesized that velocity parameters obtained from changes in clot amplitude (A) and clot elasticity (E) measured with thromboelastometry (ROTEM®, Tem International GmbH, Munich, Germany) could improve detection of fibrinolysis in whole blood obtained from children undergoing surgery for congenital heart disease. METHODS: Whole blood samples were obtained after induction of general anesthesia. Seven conditions were studied: native whole blood (baseline) and samples with progressive tissue-type plasminogen activator (t-PA) concentrations (102, 255, 512, 1024, 1535, and 2539 units/mL). We calculated velocity curves based on changes in clot amplitude and elasticity between different time points using ROTEM data. The analysis allowed for the determination of the following parameters: the maximum rate of thrombus formation based on amplitude or elasticity and the maximum rate of thrombus lysis measured based on amplitude (MTL) or maximum rate of thrombus lysis measured based on elasticity (MTLe). We compared these parameters with the lysis in relation to maximal clotting firmness and measured 30 minutes after the clotting time (LI30, in percent). RESULTS: Concentrations of t-PA ≥ 255 units/mL resulted in a decrease in LI30 (mean difference, 255 units/mL versus baseline, -31.05%, P < 0.0001) and the maximum rate of thrombus formation based on amplitude (mean difference, 255 units/mL versus baseline, -7.5, P = 0.005). Concentrations of t-PA ≥ 512 units/mL resulted in changes in maximum rate of thrombus formation based on elasticity (mean difference, 512 units/mL versus baseline, -10.9, P = 0.010), MTL (mean difference, 255 units/mL versus baseline, -3.2, P = 0.016), and MTLe (mean difference, 255 units/mL versus baseline, -7.8, P = 0.004). For t-PA concentrations ≥ 512 units/mL, clot formation was abolished. The area under the receiver operating characteristics curves did not differ between LI30, MTL, and MTLe for the detection of minimal fibrinolytic activation (102 units/mL; 0.74, 0.75, and 0.72, respectively, P = 0.708), whereas sensitivity and specificity of the cutoff values 97% for LI30, -0.3 for MTL, and -0.5 for MTLe were 52% and 85%, 83% and 45%, and 83% and 45%, respectively. CONCLUSIONS: Velocity curves based on the amplitudes or clot elasticity could provide objective measurement of clot growth and clot lysis kinetics, allowing detection of even minor fibrinolysis. Further studies are needed to assess the clinical relevance of these parameters.

Original languageEnglish (US)
Pages (from-to)486-491
Number of pages6
JournalAnesthesia and Analgesia
Volume121
Issue number2
DOIs
StatePublished - Aug 25 2015

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Thrombelastography
Elasticity
Fibrinolysis
Heart Diseases
Thrombosis
Plasminogen Activators
Tissue Plasminogen Activator
ROC Curve
General Anesthesia
Germany
Sensitivity and Specificity
Growth

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Quantification of fibrinolysis using velocity curves measured with thromboelastometry in children with congenital heart disease. / Faraoni, David; Van Der Linden, Philippe; Ducloy-Bouthors, Anne Sophie; Goobie, Susan M.; DiNardo, James A.; Nielsen, Vance G.

In: Anesthesia and Analgesia, Vol. 121, No. 2, 25.08.2015, p. 486-491.

Research output: Contribution to journalArticle

Faraoni, David ; Van Der Linden, Philippe ; Ducloy-Bouthors, Anne Sophie ; Goobie, Susan M. ; DiNardo, James A. ; Nielsen, Vance G. / Quantification of fibrinolysis using velocity curves measured with thromboelastometry in children with congenital heart disease. In: Anesthesia and Analgesia. 2015 ; Vol. 121, No. 2. pp. 486-491.
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abstract = "BACKGROUND: In this pilot study, we hypothesized that velocity parameters obtained from changes in clot amplitude (A) and clot elasticity (E) measured with thromboelastometry (ROTEM{\circledR}, Tem International GmbH, Munich, Germany) could improve detection of fibrinolysis in whole blood obtained from children undergoing surgery for congenital heart disease. METHODS: Whole blood samples were obtained after induction of general anesthesia. Seven conditions were studied: native whole blood (baseline) and samples with progressive tissue-type plasminogen activator (t-PA) concentrations (102, 255, 512, 1024, 1535, and 2539 units/mL). We calculated velocity curves based on changes in clot amplitude and elasticity between different time points using ROTEM data. The analysis allowed for the determination of the following parameters: the maximum rate of thrombus formation based on amplitude or elasticity and the maximum rate of thrombus lysis measured based on amplitude (MTL) or maximum rate of thrombus lysis measured based on elasticity (MTLe). We compared these parameters with the lysis in relation to maximal clotting firmness and measured 30 minutes after the clotting time (LI30, in percent). RESULTS: Concentrations of t-PA ≥ 255 units/mL resulted in a decrease in LI30 (mean difference, 255 units/mL versus baseline, -31.05{\%}, P < 0.0001) and the maximum rate of thrombus formation based on amplitude (mean difference, 255 units/mL versus baseline, -7.5, P = 0.005). Concentrations of t-PA ≥ 512 units/mL resulted in changes in maximum rate of thrombus formation based on elasticity (mean difference, 512 units/mL versus baseline, -10.9, P = 0.010), MTL (mean difference, 255 units/mL versus baseline, -3.2, P = 0.016), and MTLe (mean difference, 255 units/mL versus baseline, -7.8, P = 0.004). For t-PA concentrations ≥ 512 units/mL, clot formation was abolished. The area under the receiver operating characteristics curves did not differ between LI30, MTL, and MTLe for the detection of minimal fibrinolytic activation (102 units/mL; 0.74, 0.75, and 0.72, respectively, P = 0.708), whereas sensitivity and specificity of the cutoff values 97{\%} for LI30, -0.3 for MTL, and -0.5 for MTLe were 52{\%} and 85{\%}, 83{\%} and 45{\%}, and 83{\%} and 45{\%}, respectively. CONCLUSIONS: Velocity curves based on the amplitudes or clot elasticity could provide objective measurement of clot growth and clot lysis kinetics, allowing detection of even minor fibrinolysis. Further studies are needed to assess the clinical relevance of these parameters.",
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AU - Faraoni, David

AU - Van Der Linden, Philippe

AU - Ducloy-Bouthors, Anne Sophie

AU - Goobie, Susan M.

AU - DiNardo, James A.

AU - Nielsen, Vance G

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N2 - BACKGROUND: In this pilot study, we hypothesized that velocity parameters obtained from changes in clot amplitude (A) and clot elasticity (E) measured with thromboelastometry (ROTEM®, Tem International GmbH, Munich, Germany) could improve detection of fibrinolysis in whole blood obtained from children undergoing surgery for congenital heart disease. METHODS: Whole blood samples were obtained after induction of general anesthesia. Seven conditions were studied: native whole blood (baseline) and samples with progressive tissue-type plasminogen activator (t-PA) concentrations (102, 255, 512, 1024, 1535, and 2539 units/mL). We calculated velocity curves based on changes in clot amplitude and elasticity between different time points using ROTEM data. The analysis allowed for the determination of the following parameters: the maximum rate of thrombus formation based on amplitude or elasticity and the maximum rate of thrombus lysis measured based on amplitude (MTL) or maximum rate of thrombus lysis measured based on elasticity (MTLe). We compared these parameters with the lysis in relation to maximal clotting firmness and measured 30 minutes after the clotting time (LI30, in percent). RESULTS: Concentrations of t-PA ≥ 255 units/mL resulted in a decrease in LI30 (mean difference, 255 units/mL versus baseline, -31.05%, P < 0.0001) and the maximum rate of thrombus formation based on amplitude (mean difference, 255 units/mL versus baseline, -7.5, P = 0.005). Concentrations of t-PA ≥ 512 units/mL resulted in changes in maximum rate of thrombus formation based on elasticity (mean difference, 512 units/mL versus baseline, -10.9, P = 0.010), MTL (mean difference, 255 units/mL versus baseline, -3.2, P = 0.016), and MTLe (mean difference, 255 units/mL versus baseline, -7.8, P = 0.004). For t-PA concentrations ≥ 512 units/mL, clot formation was abolished. The area under the receiver operating characteristics curves did not differ between LI30, MTL, and MTLe for the detection of minimal fibrinolytic activation (102 units/mL; 0.74, 0.75, and 0.72, respectively, P = 0.708), whereas sensitivity and specificity of the cutoff values 97% for LI30, -0.3 for MTL, and -0.5 for MTLe were 52% and 85%, 83% and 45%, and 83% and 45%, respectively. CONCLUSIONS: Velocity curves based on the amplitudes or clot elasticity could provide objective measurement of clot growth and clot lysis kinetics, allowing detection of even minor fibrinolysis. Further studies are needed to assess the clinical relevance of these parameters.

AB - BACKGROUND: In this pilot study, we hypothesized that velocity parameters obtained from changes in clot amplitude (A) and clot elasticity (E) measured with thromboelastometry (ROTEM®, Tem International GmbH, Munich, Germany) could improve detection of fibrinolysis in whole blood obtained from children undergoing surgery for congenital heart disease. METHODS: Whole blood samples were obtained after induction of general anesthesia. Seven conditions were studied: native whole blood (baseline) and samples with progressive tissue-type plasminogen activator (t-PA) concentrations (102, 255, 512, 1024, 1535, and 2539 units/mL). We calculated velocity curves based on changes in clot amplitude and elasticity between different time points using ROTEM data. The analysis allowed for the determination of the following parameters: the maximum rate of thrombus formation based on amplitude or elasticity and the maximum rate of thrombus lysis measured based on amplitude (MTL) or maximum rate of thrombus lysis measured based on elasticity (MTLe). We compared these parameters with the lysis in relation to maximal clotting firmness and measured 30 minutes after the clotting time (LI30, in percent). RESULTS: Concentrations of t-PA ≥ 255 units/mL resulted in a decrease in LI30 (mean difference, 255 units/mL versus baseline, -31.05%, P < 0.0001) and the maximum rate of thrombus formation based on amplitude (mean difference, 255 units/mL versus baseline, -7.5, P = 0.005). Concentrations of t-PA ≥ 512 units/mL resulted in changes in maximum rate of thrombus formation based on elasticity (mean difference, 512 units/mL versus baseline, -10.9, P = 0.010), MTL (mean difference, 255 units/mL versus baseline, -3.2, P = 0.016), and MTLe (mean difference, 255 units/mL versus baseline, -7.8, P = 0.004). For t-PA concentrations ≥ 512 units/mL, clot formation was abolished. The area under the receiver operating characteristics curves did not differ between LI30, MTL, and MTLe for the detection of minimal fibrinolytic activation (102 units/mL; 0.74, 0.75, and 0.72, respectively, P = 0.708), whereas sensitivity and specificity of the cutoff values 97% for LI30, -0.3 for MTL, and -0.5 for MTLe were 52% and 85%, 83% and 45%, and 83% and 45%, respectively. CONCLUSIONS: Velocity curves based on the amplitudes or clot elasticity could provide objective measurement of clot growth and clot lysis kinetics, allowing detection of even minor fibrinolysis. Further studies are needed to assess the clinical relevance of these parameters.

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