Ex Vivo Effect of Apixaban on Hemostatic Biomarkers in Children With Heart Disease: A SAXOPHONE Trial Substudy

Figures

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  Figure 1. Apixaban and VKA/LMWH effects on d‐dimers. Apixaban and VKA/LMWH arms categorized by prior VKA treatment. Box plots represent the 25th to 75th percentile range, with whiskers showing the 10th to 90th percentile. The y axis is logarithmic. Asterisks indicate within‐group comparisons from baseline at week 2 or month 6. Single daggers denote significant differences within the arm by VKA treatment, while diamonds indicate differences between treatment arms with similar VKA treatment (*, †, ◆ P<0.05), (**, ††, ◆◆ P<0.01), (***, †††, ◆◆◆ P<0.001), (****, ††††, ◆◆◆◆ P<0.0001, Only significance symbols used in the figure are applicable). FEU indicates fibrinogen equivalent units; LMWH, low‐molecular‐weight heparin; and VKA, vitamin K antagonist.

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  Figure 2. Apixaban and VKA/LMWH effects on thrombin generation parameters. A, Lag time and (B) time to peak. Apixaban and VKA/LMWH arms categorized by prior VKA treatment. Box plots represent the 25th to 75th percentile range, with whiskers showing the 10th to 90th percentile. The y axis is logarithmic. Asterisks indicate within‐group comparisons from baseline at week 2 or month 6. Single daggers denote significant differences within the arm by VKA treatment, while diamonds indicate differences between treatment arms with similar VKA treatment: (*, †, ◆ P‐value <0.05), (**, ††, ◆◆ P<0.01), (***, †††, ◆◆◆ P<0.001), (****, ††††, ◆◆◆◆ P<0.0001, Only significance symbols used in the figure are applicable). LMWH indicates low‐molecular‐weight heparin; and VKA, vitamin K antagonist.

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  Figure 3. Apixaban and VKA/LMWH effects on thrombin generation parameters. A, Peak thrombin and (B) ETP. Apixaban and VKA/LMWH arms categorized by prior VKA treatment. Box plots represent the 25th to 75th percentile range, with whiskers showing the 10th to 90th percentile. The y axis is logarithmic. Asterisks indicate within‐group comparisons from baseline at week 2 or month 6. Single daggers denote significant differences within the arm by VKA treatment, while diamonds indicate differences between treatment arms with similar VKA treatment (*, †, ◆ P‐value <0.05), (**, ††, ◆◆ P‐value <0.01), (***, †††, ◆◆◆ P‐value <0.001), (****, ††††, ◆◆◆◆ P‐value <0.0001, Only significance symbols used in the figure are applicable). ETP indicates endogenous thrombin potential; LMWH, low‐molecular‐weight heparin; and VKA, vitamin K antagonist.

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  Figure 4. Correlation of the thrombin generation parameters with the apixaban levels. A, Lag time, (B) time to peak, (C) peak thrombin, and (D) ETP (all log2‐transformed) were evaluated in relation to apixaban plasma concentrations. Apixaban levels were measured using ultra‐high‐performance liquid chromatography–tandem mass spectrometry. A positive correlation was observed between apixaban concentrations and lag time and time to peak, whereas peak thrombin and ETP showed negative correlations. Red symbols represent week 2, and blue symbols represent month 6; solid lines indicate linear regression. ETP indicates endogenous thrombin potential; TGA, thrombin generation assay; and VKA, vitamin K antagonist.

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  Figure 5. Apixaban and VKA/LMWH effects on procoagulant proteins. A, FVIII and (B) fibrinogen. Apixaban and VKA/LMWH arms categorized by prior VKA treatment. Box plots represent the 25th to 75th percentile range, with whiskers showing the 10th to 90th percentile. The y axis is logarithmic. Asterisks indicate within‐group comparisons from baseline at week 2 or month 6. Single daggers denote significant differences within the arm by VKA treatment, while diamonds indicate differences between treatment arms with similar VKA treatment (*, †, ◆ P<0.05), (**, ††, ◆◆ P<0.01), (***, †††, ◆◆◆ P<0.001), (****, ††††, ◆◆◆◆ P<0.0001, Only significance symbols used in the figure are applicable). FVIII indicates factor VIII; LMWH, low‐molecular‐weight heparin; and VKA, vitamin K antagonist.

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  Figure 6. Apixaban and VKA/LMWH effects on procoagulant inhibitor proteins. A, Protein C and (B) protein S. Apixaban and VKA/LMWH arms categorized by prior VKA treatment. Box plots represent the 25th to 75th percentile range, with whiskers showing the 10th to 90th percentile. The y axis is logarithmic. Asterisks indicate within‐group comparisons from baseline at week 2 or month 6. Single daggers denote significant differences within the arm by VKA treatment, while diamonds indicate differences between treatment arms with similar VKA treatment (*, †, ◆ P‐value <0.05), (**, ††, ◆◆ P‐value <0.01), (***, †††, ◆◆◆ P‐value <0.001), (****, ††††, ◆◆◆◆ P‐value <0.0001, Only significance symbols used in the figure are applicable). LMWH indicates low‐molecular‐weight heparin; and VKA, vitamin K antagonist.