title: In vitro studies using a global hemostasis assay to examine the anticoagulation effects in plasma by the direct thrombin inhibitors: dabigatran and argatroban.
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 CaCl(2)) 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.
authors: Department of Clinical Sciences at Danderyds Hospital, Karolinska Institutet, Stockholm, Sweden. he_shu@yahoo.com
authors: Shu
authors: S
authors: He
authors: Håkan
authors: H
authors: Wallèn
authors: Niklas
authors: N
authors: Bark
authors: Margareta
authors: M
authors: Blombäck
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000097:blood / Q000494:pharmacology*; D000991:Antithrombins / Q000097:blood / Q000494:pharmacology*; D001120:Arginine / Q000031:analogs & derivatives; D001562:Benzimidazoles / Q000097:blood / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology; D001780:Blood Coagulation Tests / Q000379:methods; D000069604:Dabigatran; D004305:Dose-Response Relationship, Drug; D005260:Female; D006487:Hemostasis / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008875:Middle Aged; D010875:Pipecolic Acids / Q000097:blood / Q000494:pharmacology*; D013449:Sulfonamides; D016896:Treatment Outcome; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D001562:Benzimidazoles; D010875:Pipecolic Acids; D013449:Sulfonamides; D015091:beta-Alanine; D001120:Arginine; D000069604:Dabigatran; C031942:argatroban