Supplementary material

Vitamin K antagonists favourably modulate fibrin clot properties in patients with atrial fibrillation as early as after 3 days of treatment: relation to coagulation factors and thrombin generation

Ząbczyk Michał1, 2, Majewski Jacek2, 3, Karkowski Grzegorz2, 3, Malinowski Krzysztof Piotr4, Undas Anetta1, 2

1)  Department of Cardiac Surgery, Anaesthesiology and Experimental Cardiology, Institute of Cardiology, Jagiellonian University, Medical College, Krakow, Poland.

2)  John Paul II Hospital, Krakow, Poland.

3)  Department of Electrocardiology, Institute of Cardiology, Jagiellonian University, Medical College, Krakow, Poland.

4)  Faculty of Health Science,Jagiellonian University, Medical College, Kraków, Poland

Corresponding author:

Michał Ząbczyk, MSc

Institute of Cardiology, Jagiellonian University Medical College

80 Pradnicka St.

31-202 Krakow, Poland

Tel. +48 12 6143143

Fax +48 12 4233900

e-mail:

Table 1. Multivariate regression models for fibrin gel porosity (Ks).

Beta coefficient / 95% LCI / 95% UCI / SE / p-value
FII / -0.043 / -0.059 / -0.028 / 0.0081 / <0.0001
FVII / -0.024 / -0.035 / -0.014 / 0.0053 / <0.0001
FIX / -0.035 / -0.048 / -0.023 / 0.0065 / <0.0001
FX / -0.036 / -0.051 / -0.022 / 0.0075 / <0.0001
PC / -0.032 / -0.045 / -0.019 / 0.0069 / <0.0001
Lag / 0.42 / 0.33 / 0.52 / 0.049 / <0.0001
ETP / -0.0025 / -0.0034 / -0.0016 / 0.00044 / <0.0001
Peak / -0.0080 / -0.012 / -0.0044 / 0.0019 / <0.0001
ttPeak / 0.29 / 0.23 / 0.36 / 0.035 / <0.0001

Mixed models for Ks accounted for different time points and selected predictors. Models adjusted for age, BMI and fibrinogen (variables locked in the models).
Abbreviations: LCI, lower confidential interval bound; UCI, upper confidential interval bound; SE, standard error; F, factor; PC, protein-C; ETP, endogenous thrombin potential; ttPeak, time to peak of thrombin.

Table 2. Multivariate regression models for clot lysis time (CLT).

Beta coefficient / 95% LCI / 95% UCI / SE / p-value
FII / 0.31 / -0.044 / 0.65 / 0.17 / 0.063
FVII / 0.18 / -0.028 / 0.40 / 0.11 / 0.089
FIX / 0.22 / -0.025 / 0.48 / 0.13 / 0.096
FX / 0.29 / -0.0093 / 0.59 / 0.15 / 0.053
PC / 0.061 / -0.22 / 0.34 / 0.14 / 0.67
Lag / -2.83 / -4.97 / -0.65 / 1.12 / 0.011
ETP / 0.012 / -0.0056 / 0.030 / 0.0093 / 0.18
Peak / 0.079 / 0.0056 / 0.15 / 0.038 / 0.035
ttPeak / -1.49 / -2.92 / 0.016 / 0.80 / 0.06

Mixed models for CLT accounted for different time points and selected predictors. Models adjusted for age, BMI and fibrinogen (variables locked in the models).

For abbreviations see Table 1.

Table 3. Pairwise comparisons of time points for fibrin gel porosity (Ks) as a dependent variable with selected variables as predictors.

Selected variable / p-value / Compared
time-points / Post-hoc p-value
- / <0.0001 / 3 - 1 / 0.0189
5 - 1 / <0.0001
7 - 1 / <0.0001
28 - 1 / <0.0001
56 - 1 / <0.0001
7 - 3 / 0.030
28 - 3 / <0.0001
56 - 3 / <0.0001
28 - 5 / 0.047
56 - 5 / 0.019
FII / 0.83 / - / -
FVII / <0.0001 / 28 - 3 / <0.0001
56 - 3 / <0.0001
56 - 5 / 0.050
FIX / 0.0014 / 28 - 3 / 0.0025
56 - 3 / 0.0097
FX / 0.60 / - / -
PC / 0.0024 / 28 - 3 / 0.0025
56 - 3 / 0.0053
Lag / <0.001 / 7 - 1 / 0.041
28 - 1 / <0.001
56 - 1 / 0.0022
28 - 3 / 0.015
ETP / 0.08217 / - / -
Peak / <0.001 / 28 - 3 / <0.001
56 - 3 / <0.001
ttPeak / <0.0001 / 7 - 1 / 0.0034
28 - 1 / <0.0001
56 - 1 / <0.0001
28 - 3 / <0.0001
56 - 3 / <0.0001
28 - 5 / 0.0078
56 - 5 / 0.017

ANOVA models in mixed design. P-value less that 0.05 indicates significant difference for Ks between at least two time points. Differences between specific time points were then tested using post hoc test. Only significant differences were presented (p-value for specific pair of time points less than 0.05). Models adjusted for age, BMI and fibrinogen (variables locked in the models). For abbreviations see Table 1.

Table 4. Pairwise comparisons of time points for clot lysis time (CLT) as a dependent variable with selected parameters as predictors.

Selected variables / p-value / Compared
time-points / Post-hoc p-value
- / <0.0001 / 3 - 1 / 0.0010
5 - 1 / <0.0001
7 - 1 / <0.0001
28 - 1 / <0.0001
56 - 1 / <0.0001
5 - 3 / 0.0060
7 - 3 / <0.001
28 - 3 / <0.0001
56 - 3 / <0.0001
FII / <0.001 / 5 - 1 / <0.001
7 - 1 / <0.001
28 - 1 / <0.001
56 - 1 / <0.001
7 - 3 / 0.042
28 - 3 / 0.013
56 - 3 / 0.019
FVII / <0.0001 / 5 - 1 / <0.001
7 - 1 / <0.001
28 - 1 / <0.0001
56 - 1 / <0.0001
5 - 3 / 0.0086
7 - 3 / <0.001
28 - 3 / <0.0001
56 - 3 / <0.0001
FIX / <0.0001 / 5 - 1 / 0.0027
7 - 1 / <0.001
28 - 1 / <0.0001
56 - 1 / <0.0001
5 - 3 / 0.019
7 - 3 / 0.0019
28 - 3 / <0.0001
56 - 3 / <0.0001
FX / 0.012 / 5 - 1 / 0.015
7 - 1 / 0.026
28 - 1 / 0.014
56 - 1 / 0.016
28 - 3 / 0.027
56 - 3 / 0.031
PC / <0.0001 / 5 - 1 / <0.0001
7 - 1 / <0.0001
28 - 1 / <0.0001
56 - 1 / <0.0001
5 - 3 / 0.0082
7 - 3 / <0.001
28 - 3 / <0.0001
56 - 3 / <0.0001
Lag / <0.0001 / 3 - 1 / 0.020
5 - 1 / <0.0001
7 - 1 / <0.0001
28 - 1 / <0.0001
56 - 1 / <0.0001
5 - 3 / 0.018
7 - 3 / 0.0018
28 - 3 / <0.0001
56 - 3 / <0.001
ETP / <0.0001 / 5 - 1 / 0.0013
7 - 1 / 0.0010
28 - 1 / <0.001
56 - 1 / <0.001
5 - 3 / 0.017
7 - 3 / 0.0035
28 - 3 / <0.001
56 - 3 / <0.001
Peak / <0.0001 / 5 - 1 / 0.017
7 - 1 / 0.0043
28 - 1 / <0.001
56 - 1 / <0.001
5 - 3 / 0.012
7 - 3 / <0.001
28 - 3 / <0.0001
56 - 3 / <0.0001
ttPeak / <0.0001 / 3 - 1 / 0.013
5 - 1 / <0.0001
7 - 1 / <0.0001
28 - 1 / <0.0001
56 - 1 / <0.0001
5 - 3 / 0.010
7 - 3 / <0.001
28 - 3 / <0.0001
56 - 3 / <0.0001

ANOVA models in mixed design. P-value less that 0.05 indicates significant difference for CLT between at least two time points. Differences between specific time points were then tested using post hoc test. Only significant differences were presented (p-value for specific pair of time points less than 0.05). Models adjusted for age, BMI and fibrinogen (variables locked in the models). For abbreviations see Table 1.

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