Challenges to Laboratory Monitoring of Direct Oral Anticoagulants

Figures

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  Figure 1.. Direct oral anticoagulant (DOAC) peak and trough ranges. Dabigatran = mean and IQR; Rivaroxaban = mean and fifth and 95th percentile; Apixaban = median and fifth and 95th percentile; Edoxaban = median and (1.5 × IQR) for NVAF peak, median, and IQR for remainder—adapted from Gosselin et al.40 The small ovals represent median presenting levels for patients in the REVERSE-AD (open oval 110 ng/mL bleeding group; filled oval 73 ng/mL urgent surgery group) and ANNEXA-4 studies (149.7 ng/mL Apixaban; 211.8 ng/mL Rivaroxaban).

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  Figure 2.. Comparison of unfractionated heparin (UFH) and apixaban anti-Xa calibration curves. Methodology: Anti-Xa is performed on a standard coagulation specimen (blue top) tube containing 3.2% sodium citrate and 2.7 mL of patient whole blood, centrifuged to obtain platelet poor plasma for testing. The degree of residual Anti-Xa activity is inversely proportional to the concentration of plasma anticoagulant medication. To perform the Anti-Xa assay (including calibration data points), a fixed concentration of reagent Factor Xa is added to the test plasma. A substrate with chromophore is added and is cleaved by Factor Xa; light emission is detected at 450 nm and measured in absorbance units (mAbs). Constructing the calibration curve: The left and right boxes represent calibration curves of Anti-Xa activity using UFH and apixaban drug calibrators, respectively. For each calibration curve, known plasma concentrations of the drug are denoted under the “Target” column (UFH: IU/mL; apixaban: ng/mL) and are plotted on the X-axis. For each known plasma concentration, an Anti-Xa assay is performed based on 3 to 4 replicates (runs) of the same sample (“Replicates” column, with goal Coefficient of…