Accuracy of a Single, Heparin-Calibrated Anti-Xa Assay for the Measurement of Rivaroxaban, Apixaban, and Edoxaban Drug Concentrations: A Prospective Cross-Sectional Study

Meihandoest, Tamana; Studt, Jan‐Dirk; Méndez, Adriana; Alberio, Lorenzo; Fontana, Pierre; Wuillemin, Walter A.; Schmidt, Adrian; Graf, Lukas; Gerber, Bernhard; Amstutz, Ursula; Bovet, Cédric; Sauter, Thomas; Asmis, Lars M.; Nagler, Michael

doi:10.3389/fcvm.2022.817826

Cited by 10 publications

(14 citation statements)

References 35 publications

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“…Besides standard coagulation tests (i.e., activated partial thromboplastin time [aPTT], prothrombin time [PT]), novel indicators for anticoagulation monitoring, such as anti-Xa activity and diluted thrombin time, have been studied following the introduction of direct FXa or thrombin inhibitors. [1][2][3] On the other hand, the evolution of point-of-care (POC) tests has translated into an improvement in the clinical management of bleeding, trauma and anticoagulation therapy via viscoelastic monitoring. [4][5][6][7] The use of viscoelastic tests has also been fostered by coronavirus disease 2019 (COVID- 19) pandemic, where clinical evidence of venous (and, possibly, arterial) thrombotic events could not be explained by standard coagulation tests, which usually fell in the range of normality despite a common increase in fibrinogen and D-dimer concentration.…”

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confidence: 99%

Agreement Between Viscoelastic Coagulation Monitor (VCM), TEG 5000, and Coagulation Tests in Critically Ill Patients: A Multicenter Study

et al. 2023

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The performance of viscoelastic coagulation monitor (VCM) compared with TEG 5000 (TEG) is unknown. In this multicenter study, the authors evaluated the agreement among VCM/TEG parameters and their relationship with standard coagulation tests in critically ill patients. Viscoelastic coagulation monitor, TEG, and laboratory samples were analyzed simultaneously. Viscoelastic coagulation monitor/TEG agreement was computed by Bland and Altman’s plots, association with laboratory parameters was studied with Spearman’s correlation coefficient and random-intercept linear models. One-hundred and twenty-seven patients enrolled, 320 paired observations: 210 (65.6%) under unfractioned heparin (UFH), 94 (29.4%) under low molecular weight heparin (LMWH), 16 (5.0%) no heparin. Under UFH prolonged clot formation times and reduced the amplitude of viscoelastic tracings on both devices, especially on TEG. The type of heparin affected the agreement between VCM/TEG homolog parameters. Reaction time (TEG-R) resulted 23.1 min longer than the homolog clotting time (VCM-CT) under UFH; maximum amplitude (TEG-MA) resulted 29.5 mm higher than maximum clot firmness (VCM-MCF) under LMWH. Weak correlation was observed between VCM-CT/TEG-R and activated partial thromboplastin time (aPTT)/anti-Xa; no correlation was found between VCM-alpha/TEG-angle and fibrinogen concentration. Viscoelastic coagulation monitor-MCF showed strong (LWMH) to moderate (UFH) correlation with platelet count, while TEG-MA only showed lower correlation. Viscoelastic coagulation monitor and TEG are differently affected by heparin. The platelet count is well represented by VCM-MCF even during UFH administration.

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confidence: 99%

Agreement Between Viscoelastic Coagulation Monitor (VCM), TEG 5000, and Coagulation Tests in Critically Ill Patients: A Multicenter Study

et al. 2023

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“…It does not require equation or conversion factors in contrast to previous studies proposing tools converting "uncalibrated" anti-Xa assay results into DOAC concentrations. [7][8][9][10][11][12] Secondly, we focused on the lower part of the curve to improve precision up to 100 ng/mL, contrary to most studies. [7][8][9][10][11][12] Noteworthy, we observed a clear exponential relationship between LMWH and DOAC anti-Xa activities in this measuring range and evidenced a much better fit than using a linear relationship reported in previous studies.…”

Section: Discussionmentioning

confidence: 99%

“…[7][8][9][10][11][12] Secondly, we focused on the lower part of the curve to improve precision up to 100 ng/mL, contrary to most studies. [7][8][9][10][11][12] Noteworthy, we observed a clear exponential relationship between LMWH and DOAC anti-Xa activities in this measuring range and evidenced a much better fit than using a linear relationship reported in previous studies. These discrepancies between studies can be explained by differences among assays, deviations from manufacturer protocol (sample dilution, cali- bration curve mathematical processing), measuring range and/ or limited sample size.…”

Section: Discussionmentioning

confidence: 99%

“…The duration of anti-Xa test is 6 minutes, thus suitable for emergency. It does not require equation or conversion factors in contrast to previous studies proposing tools converting “uncalibrated” anti-Xa assay results into DOAC concentrations [ 7 - 12 ]. Secondly, we focused on the lower part of the curve to improve precision up to 100 ng/mL, contrary to most studies [ 7 - 12 ].…”

Section: Discussionmentioning

confidence: 99%

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Practical Nomogram Predicting Apixaban or Rivaroxaban Concentrations from Low-Molecular-Weight Heparin Anti-Xa Values: Special Interest in Acute Ischemic Stroke Patients

et al. 2023

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Background and PurposeIn patients with acute ischemic stroke (AIS) using a direct oral factor-Xa anticoagulant (DOAC) during the last 48 hours, a fixed plasma heparin-calibrated anti-Xa activity (0.5 IU/mL) was proposed as a threshold below which patients could be eligible for thrombolysis and/or thrombectomy. Besides, specific DOAC-calibrated anti-Xa thresholds up to 50 ng/mL have been proposed. However, specific DOAC assays are not widely available contrarily to low-molecularweight heparin (LMWH) anti-Xa activity. We developed and validated a nomogram for predicting apixaban and rivaroxaban concentrations based on LMWH anti-Xa assay. Methods Our prospective study included apixaban (n=325) and rivaroxaban (n=276) patients. On the same sample, we systematically measured specific DOAC concentration and LMWH anti-Xa activity, using STA®-Liquid-Anti-Xa (Stago) and specific DOAC-or LMWH-calibrators, respectively. The nomogram was built using quantifiable values for both assays on the derivation cohorts with a log-linear regression model. Model performances including sensitivity, specificity, and true positive rate for different thresholds were checked on the validation cohorts. ResultsThe models built from the derivation cohorts predicted that values <30 ng/mL and <50 ng/ mL DOAC thresholds corresponded to LMWH-anti-Xa values <0.10 IU/mL and <0.64 IU/mL for apixaban; <0.10 IU/mL and <0.71 IU/mL for rivaroxaban. The model accurately predicted apixaban/ rivaroxaban concentrations in the validation cohort. Conclusions This easy-to-use nomogram, developed with our reagent, allowed accurately predicting DOAC concentrations based on LMWH-anti-Xa results in emergency situations such as AIS when drug-specific assessments are not rapidly available. Using DOAC <50 ng/mL equivalent threshold, instead of the fixed LMWH <0.5 IU/mL one, would allow proposing thrombolysis to more patients.

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“…The present analysis was done as part of the Simple-Xa cross-sectional study [ 15 , 26 , 27 ]. Nine-hundred and thirty-two patients treated with rivaroxaban, edoxaban, or apixaban in clinical practice were included in 9 Swiss tertiary hospitals, between 2018 and 2019.…”

Section: Methodsmentioning

confidence: 99%

Prothrombinase-Induced Clotting Time to Measure Drug Concentrations of Rivaroxaban, Apixaban, and Edoxaban in Clinical Practice: A Cross-Sectional Study

Sathanantham

Alberio²,

Bovet

et al. 2022

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Prothrombinase-induced clotting time (PiCT) is proposed as a rapid and inexpensive laboratory test to measure direct oral anticoagulant (DOAC) drug levels. In a prospective, multicenter cross-sectional study, including 851 patients, we aimed to study the accuracy of PiCT in determining rivaroxaban, apixaban, and edoxaban drug concentrations and assessed whether clinically relevant drug levels could be predicted correctly. Citrated plasma samples were collected, and the Pefakit® PiCT was utilized. Ultra-high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed to measure drug concentrations. Cut-off levels were established using receiver-operating characteristics curves. We calculated sensitivities and specificities with respect to clinically relevant drug concentrations. Spearman’s correlation coefficient between PiCT and drug concentrations was 0.85 in the case of rivaroxaban (95% CI 0.82, 0.88), 0.66 for apixaban (95% CI 0.60, 0.71), and 0.78 for edoxaban (95% CI 0.65, 0.86). The sensitivity to detect clinically relevant drug concentrations was 85.1% in the case of 30 µg L−1 (95% CI 82.0, 87.7; specificity 77.9; 72.1, 82.7), 85.7% in the case of 50 µg L−1 (82.4, 88.4; specificity 77.3; 72.5, 81.5), and 85.1% in the case of 100 µg L−1 (80.9, 88.4; specificity 73.2%; 69.1, 76.9). In conclusion, the association of PiCT with DOAC concentrations was fair, and the majority of clinically relevant drug concentrations were correctly predicted.

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Accuracy of a Single, Heparin-Calibrated Anti-Xa Assay for the Measurement of Rivaroxaban, Apixaban, and Edoxaban Drug Concentrations: A Prospective Cross-Sectional Study

Abstract: Graphical AbstractVisual summary.

Cited by 10 publications

References 35 publications

Agreement Between Viscoelastic Coagulation Monitor (VCM), TEG 5000, and Coagulation Tests in Critically Ill Patients: A Multicenter Study

Agreement Between Viscoelastic Coagulation Monitor (VCM), TEG 5000, and Coagulation Tests in Critically Ill Patients: A Multicenter Study

Practical Nomogram Predicting Apixaban or Rivaroxaban Concentrations from Low-Molecular-Weight Heparin Anti-Xa Values: Special Interest in Acute Ischemic Stroke Patients

Prothrombinase-Induced Clotting Time to Measure Drug Concentrations of Rivaroxaban, Apixaban, and Edoxaban in Clinical Practice: A Cross-Sectional Study

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