4 research outputs found

    Monitoring direct thrombin inhibitors with routine and dedicated coagulation assays : which assay is helpful?

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    The use of direct thrombin inhibitors (DTIs) for prophylactic or therapeutic anticoagulation is increasing because of the predictable bioavailability and short half-life of these DTIs. However, in certain situations, indication of the concentration is warranted. We investigated the effects of 3 DTIs (lepirudin, argatroban, and bivalirudin) in 6 pooled plasma specimens on routine coagulation assays (activated partial thromboplastin time [aPTT], prothrombin time [PT], and thrombin time [TT]) and dedicated DTI assays (Hemoclot, HemosIL, the ecarin clotting time, and a chromogenic ecarin clotting time) on 2 coagulation analyzers. We found routine tests to be nondiscriminative between concentrations of different DTIs in the aPTT. Moreover, for PT and TT, the responses for different DTIs differed. This was similar for ecarin clotting assays. The Hemoclot and HemosIL assays showed identical linear increases for all 3 DTIs. We conclude that dedicated calibrated assays based on a diluted TT (Hemoclot and HemosIL) appear to be the most suitable for monitoring purposes

    A value proposition for trough level-based anti-TNFα drug dosing

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    \u3cp\u3eTreatment of inflammatory bowel diseases and rheumatic disorders with anti-tumor necrosis factor alpha (TNFα) drugs is expensive, while a significant proportion of patients does not show adequate clinical response. Therapeutic drug monitoring (TDM) enables patient-specific anti-TNFα therapy. The role of laboratory tests in clinical care has recently been described in a value proposition framework. It describes care processes, stakeholders, costs, risks, benefits and patient outcomes based on the use of a laboratory test in a clinical care pathway. We have applied this concept to the use of TDM for anti-TNFα drugs, describing evidence that supports the intervention and its cost effectiveness, steps that need to be adjusted in the care pathway, possible treatment algorithms and measures to assess adoption of this framework into clinical practice. For effective TDM, an assay for measurement of drug levels together with appropriate target ranges and an anti-drug-antibody assay have to be implemented. Also, instead of only reporting the drug concentration, laboratorians, pharmacists and clinicians should deliver added value by introducing a TDM-based treatment algorithm into clinical practice. Thus, to maximize effectiveness of TDM of anti-TNFα therapy in routine care, adjustment of current care pathways and cooperation of many stakeholders are needed.\u3c/p\u3

    Determination of dabigatran and rivaroxaban by ultra-performance liquid chromatography-tandem mass spectrometry and coagulation assays after major orthopaedic surgery

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    \u3cp\u3eMajor orthopaedic surgery is associated with an increased risk of venous thromboembolism. Direct oral anticoagulants (DOACs) are recommended as thromboprophylactic agents after orthopaedic surgery. Although routine monitoring of DOACs in general is not required, measuring DOAC concentration may be necessary in clinical settings. The effects of DOACs on routine coagulation assays in spiked material are studied extensively, however, few data are available on DOAC concentration in patients after major orthopaedic surgery. We measured trough and peak DOAC concentrations with UPLC-MS/MS and routine coagulation tests in a prospective study including 40 patients receiving thromboprophylactic treatment with dabigatran 220 mg od and 40 patients receiving rivaroxaban 10 mg od after major orthopaedic surgery. For rivaroxaban, the median trough concentration with UPLC-MS/MS was 17.1 ng/mL and median peak concentration was 149 ng/mL. The anti-Xa assay displayed a good correlation, but a positive bias in comparison to the reference method. Furthermore, trough levels were mostly below the LOD of the anti-Xa assay. For dabigatran, the median trough concentration with UPLC-MS/MS was 12.1 ng/mL, and median peak level was 80.8 ng/mL. A positive bias was found when results from coagulation assays were compared to UPLC-MS/MS data. However, the addition of glucuronidated metabolites to dabigatran concentration UPLC-MS/MS data generally resolved most of this bias. Age was found to have a significant influence on dabigatran pharmacokinetics, irrespective of kidney function, whereas no effect of age was found during rivaroxaban treatment. In both treatment groups, female subjects displayed faster pharmacokinetics in comparison to male subjects, although not reaching significance. We conclude that UPLC-MS/MS is the method of choice to measure trough concentrations of DOACs in patients after orthopaedic surgery. Current coagulation assays are not suited for this purpose. We found large heterogeneity in both peak and trough concentrations of DOACs, and showed that pharmacokinetics of novel oral anticoagulants may be influenced by age and gender. Whether patients with high or low trough concentrations are at increased risk for bleeding or thromboembolic events respectively remains to be established.\u3c/p\u3

    Determination of dabigatran, rivaroxaban and apixaban by ultra-performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS) and coagulation assays for therapy monitoring of novel direct oral anticoagulants

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    \u3cp\u3eBackground: Three novel direct oral anticoagulants (DOACs) have recently been registered by the Food and Drug Administration and European Medicines Agency Commission: dabigatran, rivaroxaban, and apixaban. To quantify DOACs in plasma, various dedicated coagulation assays have been developed. Objective: To develop and validate a reference ultra-performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS) method and to evaluate the analytical performance of several coagulation assays for quantification of dabigatran, rivaroxaban, and apixaban. Methods: The developed UPLC-MS/MS method was validated by determination of precision, accuracy, specificity, matrix effects, lower limits of detection, carry-over, recovery, stability, and robustness. The following coagulation assays were evaluated for accuracy and precision: laboratory-developed (LD) diluted thrombin time (dTT), Hemoclot dTT, Pefakit PiCT, ECA, Liquid anti-Xa, Biophen Heparin (LRT), and Biophen DiXal anti-Xa. Agreement between the various coagulation assays and UPLC-MS/MS was determined with random samples from patients using dabigatran or rivaroxaban. Results: The UPLC-MS/MS method was shown to be accurate, precise, sensitive, stable, and robust. The dabigatran coagulation assay showing the best precision, accuracy and agreement with the UPLC-MS/MS method was the LD dTT test. For rivaroxaban, the anti-factor Xa assays were superior to the PiCT-Xa assay with regard to precision, accuracy, and agreement with the reference method. For apixaban, the Liquid anti-Xa assay was superior to the PiCT-Xa assay. Conclusions: Statistically significant differences were observed between the various coagulation assays as compared with the UPLC-MS/MS reference method. It is currently unknown whether these differences are clinically relevant. When DOACs are quantified with coagulation assays, comparison with a reference method as part of proficiency testing is therefore pivotal.\u3c/p\u3
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