Impact of dabigatran on a large panel of routine or specific coagulation assays Laboratory recommendations for monitoring of dabigatran etexilate

被引:278
作者
Douxfils, Jonathan [1 ]
Mullier, Francois [1 ,2 ]
Robert, Severine [1 ]
Chatelain, Christian [3 ]
Chatelain, Bernard [2 ]
Dogne, Jean-Michel [1 ]
机构
[1] Univ Namur, Dept Pharm, Namur Thrombosis & Hemostasis Ctr NTHC, Namur Res Inst Life Sci NARILIS, B-5000 Namur, Belgium
[2] Catholic Univ Louvain, Hematol Lab, Namur Thrombosis & Hemostasis Ctr NTHC, Namur Res Inst Life Sci NARILIS,CHU Mt Godinne, Louvain, Belgium
[3] Catholic Univ Louvain, Dept Hematol, Namur Thrombosis & Hemostasis Ctr, CHU Mt Godinne, Louvain, Belgium
关键词
Dabigatran; monitoring; Hemoclot Thrombin Inhibitor; new oral anticoagulant; bleeding; thrombosis; DIRECT THROMBIN INHIBITOR; PROTHROMBIN COMPLEX CONCENTRATE; ATRIAL-FIBRILLATION; VENOUS THROMBOEMBOLISM; ANTICOAGULANT ACTIVITY; ORAL ANTITHROMBOTICS; CHROMOGENIC ASSAY; RIVAROXABAN; PHARMACOKINETICS; PHARMACODYNAMICS;
D O I
10.1160/TH11-11-0804
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Due to low bioavailability and high inter-individual variability, monitoring of dabigatran may be required in specific situations to prevent the risk of bleedings or thrombosis. The aim of the study was to determine which coagulation assay(s) could be used to assess the impact of dabigatran on secondary haemostasis. Dabigatran was spiked at concentrations ranging from 4.7 ng/ml to 943.0 ng/ml in pooled citrated human platelet-poor plasma. The following clotting assays were performed: prothrombin time (PT); activated partial thromboplastin time (aPTT); thrombin time (TT); ecarin clotting time (ECT); ecarin chromogenic assay (ECA); prothrombinase-induced clotting time (PiCT); activated clotting time (ACT); Hemoclot Thrombin Inhibitor (HTI) and thrombin generation assay (TGA). A concentration-dependent prolongation of PT, dPT, and aPTT was observed with aPTT being the more sensitive test. The results varied mostly due to the clotting reagent. HTI, ECT and TGA were the most sensitive tests but are not available 24 hours a day. In addition, HTI showed a linear correlation with a good reproducibility. Dabigatran induced a concentration-dependent delay and inhibition of tissue factor-induced TGA. Cut-offs related with higher risk of bleedings or thrombosis were defined for each reagent of aPTT and HTI. In conclusion, aPTT could be used for the monitoring of dabigatran and as screening test for the risk of overdose. However, because of its higher sensitivity, good reproducibility, excellent linear correlation at all doses, its simplicity of use, and possibilities of automation, HTI should be considered as the gold-standard.
引用
收藏
页码:985 / 997
页数:13
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