Effects of the oral, direct thrombin inhibitor dabigatran on five common coagulation assays

被引:231
作者
Lindahl, Tomas L. [1 ]
Baghaei, Fariba [2 ]
Blixter, Inger Fagerberg [3 ]
Gustafsson, Kerstin M. [1 ]
Stigendal, Lennart [2 ]
Sten-Linder, Margareta [4 ]
Strandberg, Karin [5 ]
Hillarp, Andreas [5 ]
机构
[1] Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden
[2] Sahlgrens Univ Hosp, Coagulat Ctr, Dept Med, Gothenburg, Sweden
[3] Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, Dept Clin Chem & Transfus Med, Gothenburg, Sweden
[4] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden
[5] Univ & Reg Labs Reg Scania, Malmo, Sweden
关键词
Dabigatran; thrombin inhibitor; interference; anticoagulant; coagulation assays; TOTAL HIP-REPLACEMENT; ECARIN CLOTTING TIME; VENOUS THROMBOEMBOLISM; PROTHROMBIN TIME; KNEE REPLACEMENT; RANDOMIZED-TRIAL; ANTICOAGULATION; ARGATROBAN; ETEXILATE; PREVENTION;
D O I
10.1160/TH10-06-0342
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Dabigatran is an oral, reversible thrombin inhibitor that has shown promising results in large clinical trials. Laboratory monitoring is not needed but the effects on common coagulation assays are incompletely known. Dabigatran was added to plasma from healthy subjects in the concentration range 0-1,000 mu g/l and analysed using several reagents for activated thromboplastin time (APTT), prothrombin time (PT), fibrinogen, antithrombin, and activated protein C resistance. Typical trough concentrations are about 50 mu g/l, peak concentrations 100-300 mu g/l. At 100 mu g/l all APTT-results were prolonged. The concentration required to double APTT ranged between 227 and 286 mu g/l, the responses for all five reagents were similar. PT-reagents were much less affected with almost no samples above INR 1.2 at 100 mu g/l. The effect was sample dilution dependent with PT Quick type more sensitive than PT Owren type methods. If a patient on dabigatran has prolonged APTT, > 90 seconds, and Quick PT INR > 2 or Owren PT INR > 1.5 over-dosing or accumulation of dabigatran should be considered. Two of four fibrinogen reagents underestimated the fibrinogen concentration considerably at expected peak concentration. Methods based on inhibition of thrombin over-estimated the antithrombin concentration, but not Xa-based. The APC-resistance methods over-estimated the APC-ratio, which may lead to miss-classification of factory Leiden patients as being normal. Different coagulation assays, and even different reagents within an assay group, display variable effects at therapeutic concentrations of dabigatran. Some of these assay variations are of clinical importance, thus knowledge is needed for a correct interpretation of results.
引用
收藏
页码:371 / 378
页数:8
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