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Inter-laboratory variability that was observed in a multicenter survey of anti-factor Xa methods for rivaroxaban [14]. In the survey, 21 laboratories were asked to measure rivaroxaban concentrations in the same plasma using their local reagents. The resultant calculated inter-laboratory CV value amounted to 25 , despite the fact that local reagents for anti-factor Xa determination were calibrated with the same set of calibration plasmas [14]. On the other hand, the lesson learnt from the attempt to standardize the anti-factor Xa assay for low molecular weight heparins PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/13485127 [15] tells us that even in the setting of rivaroxaban, standardization across reagents is far reaching. In practical terms this means that any cut-off value, which will eventually be determined on the concentration of drug obtained with a specific anti-factor Xa method, cannot be easily generalized to other reagents.Dilute thrombin and ecarin clotting times for patients on dabigatran The dilute thrombin and ecarin clotting times (dTT and ECT) are tests that can be used to measure the anticoagulant effect of dabigatran. The activated partial thromboplastin time (APTT) would also be responsive to dabigatran, but dose esponse is not linear. The PT is rather unresponsive to dabigatran. dTT is based on recording the clotting time of a mixture of test plasma and optimal amounts of thrombin. Dabigatran quenches the activity of thrombin and therefore the clotting time prolongation of dTT is proportional to the inhibitory activity 3-(2,2,2-Trifluoroethoxy)aniline hydrochloride of the drug. ECT is based on the property of the snake venom ecarin to convert prothrombin into meizothrombin, which can in turn be measured by recording the prolongation of the plasma clotting time or by a synthetic chromogenic substrate [16]. Dabigatran quenches meizothrombin and therefore the clotting time or the chromogenic activity will be proportional to the activity of dabigatran. Results for dTT or ECT are usually expressed as clotting time (seconds). They can also be expressed as ratio (patient-to-normal). Both dTT and ECT proved fairlyresponsive to dabigatran and commercial assays are available. The clotting times are approximately 2.0- or 3.0-times longer than the baseline value Fmoc-Oic-OH for dTT or ECT, respectively, when the concentration of dabigatran is 200 ng/mL [17]. The latter being the plasma concentration that can be found in patients taking 150 mg dabigatran twice daily. It is, therefore, reasonable to assume that the prolongations of the clotting times for both tests will be even higher in patients on overdosage, that is the situation when testing will probably be most useful. Cut off values for both tests could be established in clinical studies to see whether they may be useful to identify patients at increasing risk of hemorrhage. However, for these cut off to be used "universally" (i.e., regardless of the reagent used for testing) results obtained in PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/3971254 different laboratories should be comparable. Although the formulation of dTT and ECT is very simple, it is anticipated that results (even if they are expressed as ratio) will vary between laboratories. Different types (human or bovine) and concentrations of thrombin will probably be used by different commercial kits, which will ultimately make results to vary in different labs. Standardization of ECT would in principle be easier since the source of the snake venom (ecarin) that is used to activate prothrombin comes from the same source, but application of this test to different clot detection.