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

Br J Clin Pharmacol. 2014 Sep;78(3):630-8. doi: 10.1111/bcp.12366.

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.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antithrombins / pharmacokinetics
  • Antithrombins / pharmacology
  • Antithrombins / therapeutic use*
  • Atrial Fibrillation / drug therapy*
  • Benzimidazoles / pharmacokinetics
  • Benzimidazoles / pharmacology
  • Benzimidazoles / therapeutic use*
  • Dabigatran
  • Female
  • Fibrinogen / metabolism*
  • Humans
  • Linear Models
  • Male
  • Middle Aged
  • Partial Thromboplastin Time
  • Pyridines / pharmacokinetics
  • Pyridines / pharmacology
  • Pyridines / therapeutic use*
  • Thrombin Time

Substances

  • Antithrombins
  • Benzimidazoles
  • Pyridines
  • Fibrinogen
  • Dabigatran