Sensitivity of routine coagulation assays to direct oral anticoagulants: patient samples versus commercial drug-specific calibrators

Ming Sheng Lim,Kent Chapman,Anoop K. Enjeti,Priscilla Swanepoel

doi:10.1016/j.pathol.2016.07.008

Abstract

Most studies on the sensitivities of coagulation assays to direct oral anticoagulants (DOACs) are based on normal plasma spiked with anticoagulant in the laboratory. Recent studies have shown that reagent sensitivity varies significantly depending on whether spiked or patient samples are used. The aim of this study was to compare the sensitivities of routine coagulation assays in patient samples and commercial drug specific calibrators using commonly used activated partial thromboplastin time (APTT) and prothrombin time (PT) reagents (i.e., Actin FS and Neoplastine CI Plus for APTT and PT, respectively) in Australian laboratories. Samples collected at Pathology North Hunter (PN-H) for dabigatran (n=39), rivaroxaban, (n=56) or apixaban levels (n=22) between February 2013 and November 2015 were analysed and compared to two different commercial drug specific calibrators from different manufacturers for each DOAC. Our results show that dabigatran (Hyphen and Technoclone) and rivaroxaban (Stago) calibrators tend to overestimate the APTT but are similar to patient samples for PT. A cut-off DOAC level of 50ng/mL based on results from patient samples within the laboratory can be used as the lower limit which will result in prolongation of APTT for dabigatran (sensitivity 96%, n=25) and PT for rivaroxaban (sensitivity 97%, n=29), respectively. Individual laboratories should be familiar with the sensitivity of their coagulation reagents to different DOACs including differences between patient samples versus different commercial drug specific calibrators.

Highlights

Direct oral anticoagulants (DOACs) have the advantage of more predictable pharmacokinetics and pharmacodynamics compared to vitamin K antagonists such as warfarin and do not require routine laboratory monitoring
Sensitivity of activated partial thromboplastin time (APTT) and prothrombin time (PT) to DOACs in patient samples compared with commercial drug-specific calibrators
Correlation between APTT clotting times and dabigatran levels in commercial drug-specific calibrators (R2 = 1 for Hyphen and R2 = 0.9959 for Technoclone) was higher compared to patient samples (R2 = 0.7717)

Summary

Introduction

Direct oral anticoagulants (DOACs) have the advantage of more predictable pharmacokinetics and pharmacodynamics compared to vitamin K antagonists such as warfarin and do not require routine laboratory monitoring. In some situations, such as bleeding, recurrent or progressive thrombosis, emergency surgery, renal failure or liver failure, laboratory monitoring may be required. This includes baseline coagulation assays and functional anticoagulant levels. Previous studies have comprehensively evaluated the effect of DOACs on haemostasis tests in spiked or patient samples but none have compared the sensitivity of both the APTT and PT to different DOACs in patient samples versus different drug-specific commercial calibrators.[11,12,16] A recent study evaluated the use of a single drug-specific commercial calibrator for determining PT or APTT reagent sensitivity to dabigatran and rivaroxaban compared to patient

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