Laboratory testing in patients treated with direct oral anticoagulants: a practical guide for clinicians

Abstract

To cite this article: Douxfils J, Ageno W, Samama C-M, Lessire S, ten Cate H, Verhamme P, Dogn e J-M, Mullier F. Laboratory testing in patients treated with direct oral anticoagulants: a practical guide for clinicians. J Thromb Haemost 2018; 16: 209-19. Click to hear Dr Baglin's perspective on the role of the laboratory in treatment with new oral anticoagulants Summary. One of the key benefits of the direct oral anticoagulants (DOACs) is that they do not require routine laboratory monitoring. Nevertheless, assessment of DOAC exposure and anticoagulant effects may become useful in various clinical scenarios. The five approved DOACs (apixaban, betrixaban, dabigatran etexilate, edoxaban and rivaroxaban) have different characteristics impacting assay selection and the interpretation of results. This article provides an updated overview on (i) which test to use (and their advantages and limitations), (ii) when to assay DOAC levels, (iii) how to interpret the results relating to bleeding risk, emergency situations and perioperative management, and (iv) what is the impact of DOACs on routine and specialized coagulation assays. Assays for anti-Xa or anti-IIa activity are the preferred methods when quantitative information is useful, although the situations in which to test for DOAC levels are still debated. Different reagent sensitivities and variabilities in laboratory calibrations impact assay results. International calibration standards for all specific tests for each DOAC are needed to reduce the inter-laboratory variability and allow inter-study comparisons. The impact of the DOACs on hemostasis testing may cause falsepositive or false-negative results; however, these can be minimized by using specific assays and collecting blood samples at trough concentrations. Finally, prospective clinical trials are needed to validate the safety and efficacy of proposed laboratory thresholds in relation to clinical decisions. We offer recommendations on the tests to use for measuring DOACs and practical guidance on laboratory testing to help patient management and avoid diagnostic errors.

Development of new methodologies for the chromogenic estimation of betrixaban concentrations in plasma

“…The ionic force and the pH of the buffer solution are parameters that could also impact the sensitivity of a particular assay . From the results of this study and in regard to previous studies, we can suggest that betrixaban does not have a similar inhibitory profile to chromogenic anti‐Xa assays than other direct factor Xa inhibitors. This may be due to differences in Ki between the direct factor Xa inhibitors (ie, betrixaban: 0.12 nmol/L, edoxaban: 0.56 nmol/L, apixaban: 0.74 nmol/L and rivaroxaban: 0.47 nmol/L) .…”

“…The aim of this study was to propose improvements of the current chromogenic anti‐Xa assays for the measurement of betrixaban on‐therapy range. Indeed, the sensitivity of available tests is limited and does not fit with the on‐therapy range of betrixaban which is lower than the one reported with other direct factor Xa inhibitors . Three common anti‐Xa assays (STA ® ‐Liquid Anti‐Xa assay, Biophen ® Direct Xa Inhibitor ® [DiXaI], and HemosIL ® Liquid Anti‐Xa) were tested and adapted to improve their sensitivity toward the new direct factor Xa inhibitor.…”

“…Furthermore, in case of bridging therapy, the results provided by the chromogenic tests can be influenced by the presence of heparinoids. Although some chromogenic assays (ie, the Biophen ® DiXaI ® ) have been developed to be insensitive to the presence of antithrombin‐dependent FXa inhibitors such as heparins and derivatives, , it has been reported, for example, that the procedure of the Biophen ® DiXaI ® used for the determination of the low concentrations of direct factor Xa inhibitors (ie, Biophen ® DiXaI ® LOW may not warrant the specificity for the direct factor Xa inhibitors anymore). In the present work, improvements of the methodologies for chromogenic anti‐Xa assays for the estimation of betrixaban concentrations are proposed in order to improve the performances of these tests originally designed for the assessment of the direct factor Xa inhibitors apixaban, edoxaban, and rivaroxaban.…”

Periendoscopic management of direct oral anticoagulants: a prospective cohort study

“…Nevertheless, the management of such patients is challenging, because evidence-based data to guide the optimal periprocedural timing of interruption and resumption of DOACs are still lacking. Moreover, routine laboratory tests, such as the prothrombin time and activated partial thromboplastin time, have inadequate sensitivity for the quantitative assessment of the anticoagulant activity of DOACs, and drug-specific assays to measure plasma concentration are not widely available 8. This can be a major concern in any clinical situation in which assessing the intensity of anticoagulation is helpful, such as bleeding patients and those scheduled for a high-risk procedure or intervention.…”

A level‐headed approach to measuring direct oral anticoagulants: A 2‐year retrospective analysis of DOAC levels from a tertiary UK centre

“…However, the exclusion of particular cohorts of patients that are frequently encountered in clinical practice, such as those with renal impairment, the elderly and those with multiple co‐morbidities, have led some to question whether a lack of monitoring is justified . Although there is some controversy around the role of routine monitoring for DOAC, there are some situations in which measuring drug levels clearly aids clinical management . This includes but is not limited to cases involving bleeding, treatment failure, the need for an unplanned invasive procedure or surgery, evaluation prior to thrombolysis, overdose, extremes of body weight and renal dysfunction.…”