Measurement of dabigatran and rivaroxaban in primary prevention of venous thromboembolism in 106 patients, who have undergone major orthopedic surgery: an observational study

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 inter-laboratory heterogeneity of results. Anti-Xa 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 inter-individual 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.

Plasma levels of direct oral anticoagulants in real life patients with atrial fibrillation: Results observed in four anticoagulation clinics

“…DOAC inter-individual variability has been inconsistently evaluated in published reports and guidelines, and differently commented as being either low or high [5][6][7][8][9][10][11][12][13][14]. Furthermore, few studies investigated all the DOAC currently licensed for treatment of patients with atrial fibrillation.…”

“…With this in mind it was assumed the anticoagulant effect was prevalently controlled by these conditions. DOAC intra-and inter-individual variability has been previously reported [5][6][7][8][9][10][11][12][13][14], but its magnitude is still considered negligible for management. Furthermore, DOAC showed inter-individual variability of plasma concentration at steady state regardless of type of drug and patient characteristic such as renal function and body weight [9].…”

Cardiovascular Disease and HIV: Pathophysiology, Treatment Considerations, and Nursing Implications

“…44 Dabigatran is excreted primarily through the kidneys, whereas warfarin is metabolized primarily through the cytochrome P450 pathway. 25,44 Decreased renal clearance leading to toxic effects of dabigatran could result in bleeding complications, and although dabigatran does have more predictable serum levels than does warfarin, because no method of monitoring and no antidote for the former drug are available, the risk of toxic effects could outweigh the benefi ts in someone with compromised kidney function. Thus, although dabigatran is more effective in stroke prevention, warfarin is a better choice for Elmer because of the renal insuffi ciency.…”

The target-specific oral anticoagulants: practical considerations

“…21 The concentration of rivaroxaban or apixaban can be estimated by measuring the anti-Xa activity using a kit that has been calibrated for the agent of interest. [22][23][24][25][26] However, these tests will not be available in all laboratories and may have turnaround times that reduce their clinical utility.…”