Authors: Meyer Michel Samama Céline Guinet Léna Le Flem Emmanuel Ninin JeanMarc Debue
Publish Date: 2013/01/19
Volume: 35, Issue: 2, Pages: 140-146
Abstract
No routine coagulation laboratory test is recommended during rivaroxaban or dabigatran treatment However measuring drug concentration and/or anticoagulant activity can be desirable in some special clinical settings such as bleeding thrombosis recurrence or emergency surgery The effects of dabigatran etexilate and rivaroxaban on various coagulation assays have been previously studied in normal plasma spiked with increasing concentrations of the drug In contrast few data are available in routinely treated patients In order to perform and to interpret the results of these tests it is necessary to determine the usual responses of patient’s plasma We have used several coagulation tests in a prospective study including 106 patients receiving thromboprophylactic treatment with dabigatran 150 or 220 mg od and rivaroxaban 10 mg od for major orthopaedic surgery The most common tests—prothrombin time PT and activated partial thromboplastin time aPTT—give results which vary according to the reagent used To overcome this limitation we advocate the use of plasma calibrators which decreases the interlaboratory heterogeneity of results AntiXa measurement and Hemoclot a thrombin diluted clotting assay are specific assays which have been proposed for rivaroxaban and dabigatran respectively These tests conventional PT aPTT and thrombin generation TG have been performed We demonstrated that measurements of both drugs can determine reliably the drug concentration in patients’ plasmas PT is more prolonged with rivaroxaban than with dabigatran Interestingly the pattern of TG was clearly different in relation to the difference in the mechanism of action of the two new anticoagulants A significant interindividual variability of response is detected Rivaroxaban—mean Cmax 140 ng/mL extremes 0–412 induces a greater increase of PT than dabigatran aPTT is sensitive to dabigatran Rivaroxaban concentrations were in good agreement with two other studies while unexplained lower than expected concentrations were found in dabigatran patients receiving 220 mg once a day mean Cmax 60 ng/mL extremes 0–320 An interference by pantoprazole a drug which reduces dabigatran absorption could explain the observed lower than expected results
Keywords: