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Observational Study
. 2014 Sep;78(3):630-8.
doi: 10.1111/bcp.12366.

Coagulation assays and plasma fibrinogen concentrations in real-world patients with atrial fibrillation treated with dabigatran

Paul K L Chin  1 , David M Patterson, Mei Zhang, Berit P Jensen, Daniel F B Wright, Murray L Barclay, Evan J Begg
Affiliations
Observational Study

Coagulation assays and plasma fibrinogen concentrations in real-world patients with atrial fibrillation treated with dabigatran

Paul K L Chin et al. Br J Clin Pharmacol. 2014 Sep.

Abstract

Aims: In patients with atrial fibrillation prescribed dabigatran, the aim was to examine the correlation between plasma dabigatran concentrations and the three screening coagulation assays [international normalized ratio (INR), activated partial thromboplastin time (aPTT) and thrombin time (TT)] as well as the dilute thrombin time (dTT) and to examine the contribution of plasma fibrinogen concentrations to the variability in TT results.

Methods: Plasma from patients with atrial fibrillation on dabigatran were analysed for clotting times and concentrations of fibrinogen and dabigatran. Correlation plots (and associated r(2) values) were generated using these data. The variability in TT results explained by fibrinogen concentrations was quantified using linear regression.

Results: Fifty-two patients (38-94 years old) contributed 120 samples, with plasma dabigatran concentrations ranging from 9 to 408 μg l(-1) . The r(2) values of INR, aPTT, TT and dTT against plasma dabigatran concentrations were 0.49, 0.54, 0.70 and 0.95, respectively. Plasma fibrinogen concentrations explained some of the residual variability in TT values after taking plasma dabigatran concentrations into account (r(2) = 0.12, P = 0.02).

Conclusions: Of the screening coagulation assays, the TT correlated best with plasma dabigatran concentrations. Variability in fibrinogen concentrations accounts for some of the variability in the TT.

Keywords: atrial fibrillation; blood coagulation; dabigatran; fibrinogen.

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Figures

Figure 1
Figure 1
Correlation plots for 120 samples of international normalized ratio (INR; A), activated partial thromboplastin time (aPTT; B), thrombin time (TT; C) and Hemoclot® Thrombin Inhibitor (HTI; D) against plasma dabigatran concentrations. For TT, all values of TT >300 s have been set to 300 s. Continuous lines represent the lines of best fit. Dashed lines for (A), (B) and (C) are the references ranges at Canterbury Health Laboratories. The r2 values are for the line of best fit, which for (C) does not include those data with TT > 300 s in the linear regression
Figure 2
Figure 2
(A) Correlation plot of plasma fibrinogen concentrations against thrombin time (TT; for 120 samples, TT > 300 s have been set to 300 s). (B) Correlation plot of standardized residuals (from the linear regression of plasma dabigatran concentrations against TT) against standardized plasma fibrinogen concentrations (z-scores, for 45 samples with TT < 300 s). Lines of best fit are determined using the 45 samples with TT <300 s. The r2 values are for the line of best fit, and P values are for the hypothesis that the slope of the linear regression is not zero
See this image and copyright information in PMC

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