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Features of oral anticoagulant effects

Geltser I. V., Smirnova O. A., Matvienko O. Yu., Kobilyanskaya V. A., Golovina O. G., Papayan L. P.
Federal State Budgetary Inatitution, "Russian Research Institute for Hematology and Transfusiology of the Federal Medicine and Biology Agency", 2nd Sovetskaya 16, St.‑Petersburg 191024

Keywords: anticoagulant therapy, protein C system, thrombosis

DOI: 10.18087/rhj.2015.3.2085

Background. Along with the vitamin K antagonist warfarin, a group of new oral anticoagulants, including direct inhibitors of thrombin and active factor Xa (fXa), have been extensively used as the anticoagulant therapy. Already in the first days of therapy, warfarin reduces activity of important physiological anticoagulants, proteins C and S (PC, PS). Effects of fXa inhibitors on performance of natural anticoagulants in general has not been studied so far. Aim. To study effects of different anticoagulants on the PC system in patients receiving warfarin, dabigatran or rivaroxaban. Materials and methods. Patients receiving warfarin, dabigatran or rivaroxaban were evaluated. The control group included 32 healthy individuals. The PC activity (%), the general hemostatic potential of blood plasma, was evaluated using the thrombin generation test with the CAT method in two versions, with and without added rh-TM, for evaluation of the PC system anticoagulant effect. ETP values were measured, and sensitivity to TM (%) was calculated to evaluate the effectiveness of PC system performance. Results. In patients receiving warfarin, PC activity, ETP in both versions, and sensitivity to TM were considerably lower than in the control group. In patients receiving dabigatran, in spite of the normal PC level, ETP values without addition of rh-ТМ did not differ from normal, and the sensitivity to TM was sharply reduced. In the rivaroxaban treatment group, the PC activity was significantly higher than in the control group, ETP values were decreased with both versions of the method, the sensitivity to TM was high. Conclusion. Both warfarin and dabigatran facilitate the pronounced decrease in sensitivity to TM, which indicates reduced effectiveness of the PC system performance. The rivaroxaban treatment was associated with a sharp increase in this index, which suggests not only preserved function of the PC system during this treatment but also potentiation of its final effect due to the action of this inhibitor.
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Geltser I. V., Smirnova O. A., Matvienko O. Yu. et al. Features of oral anticoagulant effects. Russian Heart Journal. 2015;14 (3):154–157

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