Progress in the monitoring of direct oral anticoagulant therapy

Abstract

Summary The availability of direct oral anticoagulants (DOACs) has led to a paradigm shift in the field of anticoagulation, with DOACs increasingly being prescribed for patients in preference to vitamin K antagonists and low molecular weight heparin. Despite good experience with the use of these agents at fixed doses, there are clinical scenarios where monitoring is recommended. Data from phase III studies of the DOACs and small real‐world studies suggest a relationship between DOAC concentration and clinical events. The DOACs have differing impacts on the common tests of haemostasis and it is important that clinicians are familiar with the sensitivity of the reagents used in their laboratory to individual DOACs. The specific DOAC drug concentrations can be assayed in the laboratory, when required, to guide appropriate clinical decision‐making. Studies from the real world with sufficient numbers evaluating the association of DOAC concentrations with outcomes should be a research priority in order to understand if we could do better through dose individualisation.

DOAC plasma levels measured by chromogenic anti‐Xa assays and HPLC‐UV in apixaban‐ and rivaroxaban‐treated patients from the START‐Register

“…Our study showed a relatively high interindividual variability for the two measured DOACs, higher for rivaroxaban than apixaban and higher for trough than peak levels, in line with data in literature . The interpatient variability was similar among the chromogenic assays and HPLC‐UV, except for the method antithrombin‐supplemented whose results were influenced by the high LOQ, especially for rivaroxaban.…”

“…The assay's sensitivity and detection thresholds in terms of limits of detection (LOD) and quantification (LOQ) are method‐dependent, but the use of low‐range calibrators demonstrated to improve the assay's sensitivity for low plasma concentrations. They have been recommended as suitable methods to provide a rapid quantification of direct FXa inhibitor concentrations …”

“…They have been recommended as suitable methods to provide a rapid quantification of direct FXa inhibitor concentrations. 4,5 High-performance liquid chromatography method with ultraviolet detection (HPLC-UV) has been developed and validated for the quantitative measure of apixaban, dabigatran, and rivaroxaban concentrations. Previous studies reported that it is a reliable and cost-effective method, with a sensitivity around 10-20 ng/mL, and it can be widely available in clinical laboratories.…”

Impact of bariatric surgery on oral anticoagulants pharmacology, and consequences for clinical practice: a narrative review

“…Moreover, population pharmacokinetics will allow Monte Carlo simulations to be carried out to test different hypotheses without the need to involve new patients [62]. In the absence of PK/PD reference markers that would predict the occurrence of haemorrhagic or thrombotic clinical events [63], prospective follow‐up of treated patients should be conducted to determine the risk benefit balance of DOACs in this population.…”

Anticoagulants and Their Monitoring

“…12 In this regard, thrombin generation tests (thrombin clotting time or ecarin clotting time) or thromboelastography may perform better compared with the INR for predicting bleeding risk, but is used for monitoring anticoagulant therapy in routine clinical practice. 13,14 In general, target INR for patients with cirrhosis is a goal INR of 1.0 higher than baseline, if the baseline INR is >1.5. Vitamin K, prothrombin complex concentrates, and fresh frozen plasma can be used to reverse bleeding in patients receiving warfarin.…”