Journal of Thrombosis and Thrombolysis

, Volume 35, Issue 2, pp 131–139

In vitro studies using a global hemostasis assay to examine the anticoagulation effects in plasma by the direct thrombin inhibitors: dabigatran and argatroban

  • Shu He
  • Håkan Wallèn
  • Niklas Bark
  • Margareta Blombäck
Article

DOI: 10.1007/s11239-012-0791-x

Cite this article as:
He, S., Wallèn, H., Bark, N. et al. J Thromb Thrombolysis (2013) 35: 131. doi:10.1007/s11239-012-0791-x

Abstract

This study aimed to assess whether a global hemostatic assay we developed can measure the anticoagulant effects of the direct thrombin inhibitors (DTIs)—dabigatran and argatroban. A normal plasma pool (NPP) spiked with one of the DTIs and five plasma samples from patients with coronary heart disease spiked with dabigatran were examined. Fibrin formation and fibrin degradation were initiated by adding recombinant tissue factor (together with washed-frozen-thawed platelets and CaCl2) and recombinant tissue plasminogen activator. Fibrin optical density (OD) was recorded, based on which coagulation activation profile (Cp) and fibrinolysis activation profile (Fp) were determined. Moreover, the sum of OD values registered over time (fibrin OD-sum) was calculated to reflect the capacity of fibrin formation under the general effect by Cp and Fp. The endogenous thrombin potential (ETP) and the standard clotting markers i.e., activated partial thromboplastin time (APTT) and prothrombin time expressed as International Normalized Ratio (INR) were also analyzed. Results demonstrated that APTT, INR and ETP could detect the effects of the DTIs except for INR in NPP containing dabigatran. In our global assay, the DTIs depressed the fibrin formation (shown as decreased fibrin OD-sum value) by leading to decrease of Cp and increase of Fp. Thus, our global assay which examines both fibrin formation and degradation seems more advantageous than the other methods mentioned above, as regards the possibility of being a laboratory tool to monitor the antithrombotic therapy with DTIs.

Keywords

Global hemostasis assayThrombin inhibitorXa inhibitorFibrin formationFibrin stability to fibrinolysisMonitor

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Shu He
    • 1
    • 3
  • Håkan Wallèn
    • 2
  • Niklas Bark
    • 3
    • 4
  • Margareta Blombäck
    • 3
  1. 1.Department of Clinical Sciences at Danderyds HospitalKarolinska InstitutetStockholmSweden
  2. 2.Division of Cardiovascular Medicine, Department of Clinical Sciences at Danderyds HospitalKarolinska InstitutetStockholmSweden
  3. 3.Division of Clinical Chemistry, L2-5/Coagulation Research, Department of Molecular Medicine & SurgeryKarolinska Institutet, Karolinska University HospitalStockholmSweden
  4. 4.Department of Clinical NeuroscienceKarolinska InstitutetStockholmSweden