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

Abstract

A new generation of antithrombotic agents has recently emerged. These provide direct inhibition of either thrombin (factor IIa [FIIa]) or FXa, and are increasingly replacing the classical anticoagulants (heparin and coumarins such as warfarin) in clinical practice for a variety of conditions. These agents have been designated several acronyms, including NOACs, DOACs, and TSOACs, respectively, referring to ew (ovel; on?vitamin K antagonist) ral ntioagulant, irect ral ntioagulant, and arget-pecific ral ntioagulant, and currently include dabigatran (FIIa inhibitor), and rivaroxaban, apixaban, edoxaban, and betrixaban (FXa inhibitors). The pervading mantra that NOACs do not require laboratory monitoring is countered by ongoing recognition that laboratory testing for drug effects is needed in many situations. Moreover, since these agents ?do not require? laboratory monitoring, some clinicians inappropriately take this to mean that they do not affect hemostasis tests. This review aims to briefly review the laboratory studies that have evaluated the NOACs against a wide range of laboratory assays to assess utility for qualitative or quantitative measurements of these drugs, as well as interferences that may cause misdiagnosis of hemostatic defects. Point of care testing, including use of alternate samples such as urine and serum, is also under development but is not covered extensively in this review. The main aims of this article are to provide practical guidance to general laboratory testing for NOACs, as well as to help avoid diagnostic errors associated with hemostasis testing performed on samples from treated patients, as these currently comprise major challenges to hemostasis laboratories in the era of the NOACs.

Long-term prescribing of new oral anticoagulants

“…15 In contrast, the role of the tests in guiding dosing in the ambulatory setting remains controversial, partly because of questions about the choice of test and target range.…”

“…15 However, as the relationships between each of these tests and anticoagulant concentrations varies by drug and by laboratory, interpretation should be performed in consultation with local specialists. Specific advice about interpretation of coagulation tests is available from the Australasian Society of Thrombosis and Haemostasis.…”

Practical guidance on the use of laboratory testing in the management of bleeding in patients receiving direct oral anticoagulants

“…A large number of studies have consistently demonstrated the accuracy and sensitivity of drug-specific anti-factor Xa chromogenic assays for the quantitative measurement of rivaroxaban, as summarized in a comprehensive literature review. 31 These assays (calibrated with rivaroxaban) can measure a wide range of rivaroxaban plasma concentrations that cover the expected levels after therapeutic doses ( Figure 1 ) and are, therefore, recommended by the EHRA and the rivaroxaban – Summary of Product Characteristics. 1 , 5 However, the longer turnaround time to obtain the test results makes them less convenient than PT in emergency situations.…”

New Insights into the Pros and Cons of the Clinical Use of Vitamin K Antagonists (VKAs) Versus Direct Oral Anticoagulants (DOACs)

“…Moreover, monitoring dabigatran plasma concentrations has the potential to improve safety and efficacy profiles as compared to fixed dosage [ 58 , 59 ]. Therapeutic drug monitoring of DOACs is supported by population studies which demonstrated a wide range of plasma dabigatran concentrations in different patient groups and at different time points although drug concentrations remained within the putative therapeutic range [ 60 ]. Variations in plasma concentration are ascribed to drug interactions, differences in absorption in the gastrointestinal tract, and clearance by the liver and kidneys [ 61 ].…”