Laboratory assessment of rivaroxaban: a review

Abstract

Research into new anticoagulants for preventing and treating thromboembolic disorders has focused on targeting single enzymes in the coagulation cascade, particularly Factor Xa and thrombin, inhibition of which greatly decreases thrombin generation. Based on the results of phase III clinical trials, rivaroxaban, a direct Factor Xa inhibitor, has been approved in many countries for the management of several thromboembolic disorders. Owing to its predictable pharmacokinetic and pharmacodynamic characteristics, fixed-dose regimens are used without the need for routine coagulation monitoring. In situations where assessment of rivaroxaban exposure may be helpful, anti-Factor Xa chromogenic assays (in tandem with standard calibration curves generated with the use of rivaroxaban calibrators and controls) could be used. It is important to note that test results will be affected by the timing of blood sampling after rivaroxaban intake. In addition, the anti-Factor Xa method measures the drug concentration and not the intensity of the drug’s anticoagulant activity, and a higher than expected rivaroxaban plasma level does not necessarily indicate an increased risk of bleeding complications. Therefore, clinicians need to consider test results in relation to the pharmacokinetics of rivaroxaban and other patient risk factors associated with bleeding.

The laboratory and the direct oral anticoagulants

“…This result expression has been proposed for dilute-TT 12 and anti-FXa assays. 18 Whether clotting time prolongation or drug concentration equivalent is the preferred way of expressing results has not yet been established.…”

“…Moreover, standardization as assessed in a collaborative survey is poor: the average interlaboratory variation of results obtained while measuring the same rivaroxaban-spiked plasmas by means of local methods was high (ie, 25%). 18 Conversely, the PT is readily available even in an emergency and its standardization could be obtained as described 19,20 by expressing results as PT ratio (patientto-normal) corrected by means of a sensitivity index. Such an index can be determined for working thromboplastins relative to an international standard.…”

Peak plasma concentration of direct oral anticoagulants in obese patients weighing over 120 kilograms: A retrospective study

“…We also examined the proportion of patients who had a plasma peak concentration of apixaban, or rivaroxaban below the fifth percentile or plasma peak concentration of dabigatran below the 10th percentile (the lowest percentile reported in the literature for dabigatran);14, 15, 16, 17 the proportion of patients who were switched to warfarin based on the discretion of the treating physician; and the proportion of patients with recurrent VTE and/or stroke during the study follow‐up since the peak concentration was measured. The latter two outcomes were assessed in 22 patients from the anticoagulation clinics.…”

Laboratory Testing in the Era of Direct or Non–Vitamin K Antagonist Oral Anticoagulants: A Practical Guide to Measuring Their Activity and Avoiding Diagnostic Errors

“…The clot-based factor assays are mildly affected by apixaban, 31 This is summarized in ►Table 1 and ►Fig. 3.…”

“…HTI/dTT and ECT/ECA assays can be used for a more accurate estimation of the anticoagulant effect of the drug and to "quantify" drug level, [15][16][17][19][20][21]24,26,27,[29][30][31][34][35][36][37][41][42][43][44][45][46][47] although the former tests (HTI/dTT) appear overall better standardized for this purpose than the latter (ECT/ECA).…”