Laboratory testing of rivaroxaban in routine clinical practice: When, how, and which assays

Figures & data

Table I. Guidance on laboratory assays to measure rivaroxaban in plasma.

	Assays	Advantages	Disadvantages	Clinical situations in which testing might be useful
Quantitative measurement	Chromogenic anti-Factor Xa assay using rivaroxaban calibrators	• Specific; Sensitive; Standardized; Correlates with HPLC MS/MS	• Not (yet) available in every laboratory	•Suspected accumulation of drug (i.e. fragile elderly patients with renal insufficiency) • Overdose • Acute renal failure • Bleeding complications or thrombosis during treatment • Emergency situations (if available in time): • Prior to urgent surgery; Life-threatening bleeding; Stroke (if fibrinolytic treatment indicated); Acute PCI (if heparin bolus indicated)
Qualitative measurement	Rivaroxaban-sensitive PT (i.e. Neoplastin CI Plus, RecombiPlasTin) measured in seconds	• Widely available	• Non-specific; Not standardized; Laboratory might need an additional rivaroxaban-sensitive PT reagent if the routine-PT reagent is insensitive to rivaroxaban; Abnormal PT baseline value possible (e.g. in hepatic insufficiency)	• Emergency situations: When an anti-Factor Xa assay is not available
Not recommended	Rivaroxaban-insensitive PT; aPTT; TT

aPTT = activated partial thromboplastin time; HPLC MS/MS = high-performance liquid chromatography–tandem mass spectrometry; PCI = percutaneous coronary intervention; PT = prothrombin time; TT = thrombin time.

Figure 1. Prothrombin time (PT) measured A: in seconds (13); and B: as INR (Lindhoff-Last, unpublished data) in patients undergoing hip or knee replacement surgery taking rivaroxaban 10 mg once daily. Results are median values (n = 47). INR = international normalized ratio.

Figure 2. Transitioning from rivaroxaban to a vitamin K antagonist (VKA). *Approved rivaroxaban dose for treatment of deep vein thrombosis (DVT), and prevention of recurrent DVT and pulmonary embolism following an acute DVT, and for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation. INR = international normalized ratio.

Table II. Plasma concentrations of rivaroxaban at steady state in different patient populations.

Patient population/clinical setting	Rivaroxaban dose	Ctrough (μg/L)^a	Cmax (μg/L)^b
VTE prevention after total hip replacement surgery	10 mg o.d.	9 (1–38)^c	125 (91–196)^c
DVT treatment (continued treatment)	20 mg o.d.	26 (6–87)^d	270 (189–419)^d
Stroke prevention in patients with AF (CrCl > 50 mL/min)	20 mg o.d.	44 (12–137)^e	249 (184–343)^e
Stroke prevention in patients with AF (CrCl ≤ 50 mL/min)	15 mg o.d.	57 (18–136)^e	229 (178–313)^e

AF = atrial fibrillation; C_max = maximum plasma concentration; CrCl = creatinine clearance; C_trough = minimum plasma concentration; DVT = deep vein thrombosis; o.d. = once daily; VTE = venous thromboembolism.

^aDefined as samples collected 20–28 hours after dosing.

^bDefined as samples collected 2–4 hours after dosing.

^cMedian estimated values (5th–95th percentile range) in phase II studies in patients undergoing total hip replacement surgery (27).

^dParameter estimates at steady state—geometric means (5th–95th percentile range) in phase II studies in the acute treatment of DVT (28).

^eParameter estimates at steady state—geometric means (5th–95th percentile range) in stroke prevention in patients with AF (Bayer HealthCare Pharmaceuticals and Janssen Research & Development, LLC: data on file).

Mani H, Hesse C, Stratmann G, Lindhoff-Last E. Rivaroxaban differentially influences ex vivo global coagulation assays based on the administration time. Thromb Haemost. 2011;106:156–64.

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