Laboratory Assessment of Hemostatic and Anticoagulant Therapy

Adcock, Dorothy M.; Gosselin, Robert

doi:10.1055/s-0037-1601051

Cited by 9 publications

(12 citation statements)

References 9 publications

(9 reference statements)

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“…We will not detail the different methods of measuring DOAC concentrations or activity in this article but refer the reader to recent excellent reviews detailing the different laboratory methods . However, we stress that it is not the drug concentration by itself that interests those taking care of anticoagulated patients but rather the biological effect which is of most importance, namely, how does the measured effect reflect the clinical antithrombotic effect.…”

Section: How and What To Monitor?mentioning

confidence: 99%

“…The DOACs are small molecules whose concentrations can be measured accurately using mass spectrometry . Such tests, however, are not widely available or practical for most laboratories that need to offer 24/7 immediate testing and reporting of results to clinicians.…”

Section: How and What To Monitor?mentioning

confidence: 99%

“…Dabigatran, thus, can be measured around the clock using calibrated activity assays, that is, dabigatran with the dilute sample thrombin time (dsTT), ecarin clotting time (ECT), or ecarin chromogenic assay using special dabigatran calibrators. The anti‐Xa agents can likewise be measured using anti‐Xa chromogenic assays using a special calibrator where the anti‐Xa drug being measured each time is used to calibrate the anti‐Xa assay . When a calibrated anti‐Xa drug assay is not available, some suggest that the anti‐Xa assay calibrated with heparin or low molecular weight heparin can be used to estimate the amount of a Xa inhibitor but such reporting is mainly useful to assess low anti‐Xa concentrations as peak levels of the anti‐Xa agents may lead to anti‐Xa units as high as 5‐9 IU/mL which is well outside the upper range of the typical assay .…”

Section: How and What To Monitor?mentioning

confidence: 99%

“…The DOACs are small molecules whose concentrations can be measured accurately using mass spectrometry. 12,13 Such tests, however, are not widely available or practical for most laboratories that need to offer 24/7 immediate testing and reporting of results to clinicians. Automated activity assays fulfilling such requirement do, nonetheless, exist that correlate well with the gold standard mass spectrometric results.…”

Section: Direct Oral Anticoagulantsmentioning

confidence: 99%

“…The anti-Xa agents can likewise be measured using anti-Xa chromogenic assays using a special calibrator where the anti-Xa drug being measured each time is used to calibrate the anti-Xa assay. 12,13 When a calibrated anti-Xa drug assay is not available, some suggest that the anti-Xa assay calibrated with heparin or low molecular weight heparin can be used to estimate the amount of a Xa inhibitor but such reporting is mainly useful to assess low anti-Xa concentrations as peak levels of the anti-Xa agents may lead to anti-Xa units as high as 5-9 IU/mL which is well outside the upper range of the typical assay. 13 Usually, the DOACs should be assessed as trough concentrations although random measurements will be done in acute situations.…”

Section: Direct Oral Anticoagulantsmentioning

confidence: 99%

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Oral anticoagulant monitoring: Are we on the right track?

Önundarson

Flygenring

2019

Int J Lab Hematology

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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.

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Section: How and What To Monitor?mentioning

confidence: 99%

Section: How and What To Monitor?mentioning

confidence: 99%

Section: How and What To Monitor?mentioning

confidence: 99%

Section: Direct Oral Anticoagulantsmentioning

confidence: 99%

Section: Direct Oral Anticoagulantsmentioning

confidence: 99%

See 3 more Smart Citations

Oral anticoagulant monitoring: Are we on the right track?

Önundarson

Flygenring

2019

Int J Lab Hematology

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2019 Eberhard F. Mammen Award Announcements: Part I—Most Popular Articles

Favaloro

2019

Semin Thromb Hemost

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Current and Emerging Direct Oral Anticoagulants: State-of-the-Art

Lippi

Gosselin

Favaloro

2019

Semin Thromb Hemost

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Anticoagulant drugs comprise a specific subcategory of antithrombotic agents that act to inhibit blood coagulation at various stages, reducing clot development and ultimately lowering the risk of developing new-onset or recurrent thrombosis. Although the long history of anticoagulant drugs has been characteristically shaped by coumarin and heparin derivatives, a new generation of direct oral anticoagulants (DOACs), which specifically inhibit thrombin or activated factor X, combine many advantages of their progenitor drugs, and hence are prepotently revolutionizing the landscape of antithrombotic therapy. Several drugs (apixaban [BMS-562247], dabigatran [BIBR953], edoxaban [DU-1766], rivaroxaban [BAY 59–7939]) have already received widespread approval by national or supranational medicinal agencies. This narrative article provides a state-of-the-art for these and for several other DOACs at different stages of clinical evaluation (betrixaban, darexaban, eribaxaban, letaxaban, nokxaban), and certain others whose development has been discontinued (AZD-0837, fidexaban, LY517717, odiparcil, otamixaban, TTP889, and ximelagatran). What clearly emerges from our analysis is that DOACs sharing very similar mechanisms of action are still characterized by different efficacy and safety profiles. This not only depends on biochemical, biological, and pharmacokinetic characteristics, but also on lack of standardization between different clinical trials in terms of targeted disease, patient recruitment, sample size, duration and endpoints, as well as lack of harmonization around procedures used for drug licensing. These factors contribute to challenging the minds of physicians, who may find difficulty navigating their way through multiple indications, different pharmacological profiles, various side effects, and specific drug-to-drug interactions. Such considerations also burden laboratory professionals, who may face organizational and economic challenges in developing and/or implementing multiple assays to assess the pharmacodynamics (effect on coagulation) or pharmacokinetics (drug levels) of DOACs.

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Laboratory Assessment of Hemostatic and Anticoagulant Therapy

Cited by 9 publications

References 9 publications

Oral anticoagulant monitoring: Are we on the right track?

Oral anticoagulant monitoring: Are we on the right track?

2019 Eberhard F. Mammen Award Announcements: Part I—Most Popular Articles

Current and Emerging Direct Oral Anticoagulants: State-of-the-Art

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