Oral anticoagulant monitoring: Are we on the right track?

Abstract

Vitamin K antagonists (VKAs) cannot be administered without regular monitoring in order to assure their efficacy and safety. Indeed, if well managed, the VKAs appear to be no less efficacious or safe than the newer direct oral anticoagulants (DOACs). Although it is claimed that no regular monitoring of the DOACs is needed, their levels are increasingly being measured under a variety of circumstances, for example, prior to surgery, in suspected overdose, to confirm effective reversal, in patients with malabsorption and to assess patient compliance. Although no therapeutic range has been identified for the DOACs, it has been demonstrated for dabigatran and edoxaban that their antithrombotic effect increases gradually with increasing concentrations and that the risk of major bleeding also gradually increases. Furthermore, it has been determined that almost all dabigatran‐related thrombotic events occur in patients with the lowest quartile concentration of the drug. This suggests that to assure an ideal effect of DOACs in all patients taking them, some form of regular monitoring and dose tailoring should be performed. For the vitamin K antagonists, the best outcome is obtained using formal algorithms and centralized management. Furthermore, data suggest that replacing the standard prothrombin time as a monitoring test may increase the stability of VKA anticoagulation with consequent reduction in thromboembolism without an increase in bleeding. Thus, it is likely that the outcome of all current oral anticoagulants can be improved in the coming years by improving monitoring and tailoring their effect.

Clinical guideline on reversal of direct oral anticoagulants in patients with life threatening bleeding

“…For dabigatran, this has been shown in the RE-LY clinical RCT 89 . Although no therapeutic range has been identified for the DOACs, it has been demonstrated for dabigatran and edoxaban that their antithrombotic effect increases gradually with increasing concentrations and that the risk of major bleeding also gradually increases 88 . Multiple logistic regression (c-statistic 0.715, 95% CI: 0.69 to 0.74) showed major bleeding risk increased with dabigatran exposure ( P < 0.0001), age ( P < 0.0001), ASA use ( P < 0.0003) and diabetes ( P = 0.018) as significant covariates 89 .…”

“…For DOACs, the important clinical issue is if their measured concentrations (or activity based on calibrated concentrations) reflect their biological effect 88 . For dabigatran, this has been shown in the RE-LY clinical RCT 89 .…”

“…For DOACs, the important clinical issue is if their measured concentrations (or activity based on calibrated concentrations) reflect their biological effect. 88 For dabigatran, this has been shown in the RE-LY clinical RCT. 89 Although no therapeutic range has been identified for the DOACs, it has been demonstrated for dabigatran and edoxaban that their antithrombotic effect increases gradually with increasing concentrations and that the risk of major bleeding also gradually increases.…”

Replacement of traditional prothrombin time monitoring with the new Fiix prothrombin time increases the efficacy of warfarin without increasing bleeding. A review article

“…Measuring DOAC anticoagulant effect may have useful applications [ 50 ] but no single test can be used for this purpose [ 50 ]. A test using highly diluted thromboplastin, the tissue thromboplastin inhibition test (a dilute PT (dPT) assay) used in the past for lupus anticoagulant detection was known to be sensitive to heparin, thrombin and anti-Xa inhibitors but not to pentasaccharide [ 51 ].…”