Non-VKA Oral Anticoagulants: Accurate Measurement of Plasma Drug Concentrations

Table 2

Advantages and drawbacks of coagulation tests that could be used to estimate plasma concentrations of NOACs or to estimate the relative intensity of anticoagulation.

	Molecule(s)	Utility	Laboratory experience	Availability	Sensitivity^†/; specificity	Dependence of the reagent	Cut-off for a risk of bleeding; (unit(s) of expression)
aPTT	Dabigatran	Limited: poorly reflects the intensity of anticoagulation	Not required	24/7—all laboratories	±100 ng/mL/no	Yes	Yes: depends on the indication and the reagent (ratio and seconds)
TT	Dabigatran	Limited: only to exclude the presence of dabigatran. Useful in the perioperative setting	Not required	24/7—all laboratories	Too sensitive^‡/no	Yes	Not established
dTT	Dabigatran	Proven: accurately estimates the plasma concentrations—results expressed in ng/mL	Required: requirement of calibrators and controls	Requirement of trained personnel—only in specialized laboratories	±10 ng/mL/no	No	Yes: depends on the indication (ng/mL)
ECT	Dabigatran	Limited: standardisation and validation required	Required: interlot variability probably requiring calibrators and controls	Requirement of trained personnel—only in specialized laboratories	±15 ng/mL/no	Probably not but an interlot variability has been reported	Yes: depends on the indication (ratio and seconds)
ECA	Dabigatran	Proven: accurately estimates the plasma concentrations—results expressed in ng/mL	Required: requirement of calibrators and controls	Requirement of trained personnel—only in specialized laboratories	±10 ng/mL/no	No	Yes: depends on the indication (ng/mL)
PT	Rivaroxaban	Limited: poorly reflects the intensity of anticoagulation	Not required	24/7—all laboratories	from ±100 to >500 ng/mL (depending on the reagent)/no	Yes	Not established
Chromogenic anti-Xa assays	Rivaroxaban/; Apixaban	Proven: accurately estimates the plasma concentrations—results expressed in ng/mL	Required: requirement of calibrators and controls	Requirement of trained personnel—only in specialized laboratories	±10 ng/mL/yes-no (depending on the anti-Xa assay)	No	Not established
DRVV-T	Dabigatran/; Rivaroxaban/; Apixaban	Partially proven: confirmation should be done in plasma samples from patients treated with dabigatran and apixaban	Not required	Only in specialized laboratories	±100 to 200 ng/mL (depending on the reagent and the molecule)/no	Yes, but less importantly than for PT or aPTT	Not established

aPTT: activated partial thromboplastin time; DRVV-T: dilute Russell’s viper venom time; dTT: dilute thrombin time; ECA: ecarin chromogenic assay; ECT: ecarin clotting time; PT: prothrombin time; TT: thrombin time.
^†Sensitivity is defined as the concentration required to double or to halve the clotting time (for chronometric assays) or the OD/min (for chromogenic assays), respectively.
^‡Plasma concentrations of dabigatran >30 ng/mL frequently excess the maximal time measured on most coagulometers.