Mass spectrometry in the therapeutic drug monitoring of direct oral anticoagulants. Useful or useless?

Douxfils, Jonathan; Pochet, Lionel; Lessire, Sarah; Vancraeynest, Christelle; Dogné, Jean‐Michel; Mullier, François

doi:10.1016/j.trac.2016.01.029

Cited by 20 publications

(20 citation statements)

References 81 publications

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“…Finally, the conventional HTI (a diluted TT) is affected by a limit of quantitation between 30 and 50 ng/mL, 6 and not 20 ng/mL as reported by the authors. 5 This limit of quantitation was not able to measure accurately DOAC concentrations encountered in the perioperative setting.…”

mentioning

confidence: 78%

“…In addition, activated partial thromboplastin time is not specific to dabigatran and the sensitivity depends on the reagent and the coagulometer. 6 …”

mentioning

confidence: 99%

“…This percentage could be different in other laboratories, as TT is not standardized and is affected by many variables (ie, type of thrombin or the clot detection method). 6 Therefore, it is not possible to draw conclusions from multicenter studies in which centers use different procedures for TT. Thus, a normal TT can only reasonably exclude the presence of clinically relevant concentrations of dabigatran.…”

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confidence: 99%

“…Therefore, it is recommended to adapt the calibration and use an appropriate method for the measurements of low DOAC concentrations (ie, using the HTI LOW or the ECA-II for dabigatran) as they were found more accurate than the standard method (HTI). 6 …”

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confidence: 99%

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Periprocedural Management of Direct Oral Anticoagulants Should Be Guided by Accurate Laboratory Tests

Lessire

Douxfils

Dincq

et al. 2016

Regional Anesthesia and Pain Medicine

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mentioning

confidence: 78%

“…In addition, activated partial thromboplastin time is not specific to dabigatran and the sensitivity depends on the reagent and the coagulometer. 6 …”

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Periprocedural Management of Direct Oral Anticoagulants Should Be Guided by Accurate Laboratory Tests

Lessire

Douxfils

Dincq

et al. 2016

Regional Anesthesia and Pain Medicine

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“…However, in clinical practice, there is rarely a need to accurately determine a very high level of rivaroxaban and accurate estimation of low or therapeutic levels is more often clinically relevant. The anti‐Xa assay is more appropriate for clinical laboratory use as it more available and less labour‐intense than HPLC‐MS/MS . The LLOQ for the HemoSIL ® anti‐Xa assay was 20 ng/mL due to the matrix effect at the lower end of the calibration curve.…”

Section: Discussionmentioning

confidence: 99%

Measurement of rivaroxaban concentrations demonstrates lack of clinical utility of a PT, dPT and APTT test in estimating levels

Thöm

Cameron

Robertson

et al. 2018

Int J Lab Hematology

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The PT and aPTT show poor correlation with rivaroxaban levels measured by calibrated anti-Xa and HPLC-MS/MS assays. A normal combined PT and APTT identified low rivaroxaban levels with high specificity but lacked sensitivity. The dPT assay at several dilutions could not be used to quantify rivaroxaban in clinical samples. The utility of these PT, aPTT and dilute PT assays in a clinical setting is very limited, and results generated must be interpreted with caution.

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A high‐throughput liquid chromatography‐tandem mass spectrometry method for simultaneous determination of direct oral anticoagulants in human plasma

Žideková

Pršo

Brisudová

et al. 2023

J of Separation Science

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Direct oral anticoagulants are widely used in many indications to prevent thromboembolic events. Routine therapeutic monitoring is not required; however, there is increasing evidence suggesting the benefit of plasma level measurement in some situations. In addition, laboratory monitoring might help improve patient and drug non‐compliance and thus individualize therapy. In the present study, we developed a sensitive and high throughput ultra‐high‐performance liquid chromatography‐tandem mass spectrometry method for simultaneous quantification of apixaban, dabigatran, edoxaban, and rivaroxaban in human plasma. A one‐step extraction procedure in 96‐well formate for phospholipid and protein removal was used for sample pre‐treatment, and analytes were separated using gradient elution over 4.2 min. Analytes were detected on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring mode. The method was validated according to the European Medicine Agency guideline for the selectivity, linearity, and lower limit of detection, precision and accuracy, matrix effects, extraction recovery, carryover, dilution integrity, and stability over a concentration range of 3.0–1000 ng/ml for all analytes. The validated method was applied to real clinical samples of patients treated with one of the drugs. Therefore, we can conclude that our method is suitable for therapeutic drug monitoring of direct oral anticoagulants.

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Mass spectrometry in the therapeutic drug monitoring of direct oral anticoagulants. Useful or useless?

Cited by 20 publications

References 81 publications

Periprocedural Management of Direct Oral Anticoagulants Should Be Guided by Accurate Laboratory Tests

Periprocedural Management of Direct Oral Anticoagulants Should Be Guided by Accurate Laboratory Tests

Measurement of rivaroxaban concentrations demonstrates lack of clinical utility of a PT, dPT and APTT test in estimating levels

A high‐throughput liquid chromatography‐tandem mass spectrometry method for simultaneous determination of direct oral anticoagulants in human plasma

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