Evaluation of the in vitro stability of direct oral anticoagulants in blood samples under different storage conditions

Thuile, Katharina; Giacomuzzi, Katia; Jani, Erika; Marschang, Peter; Mueller, Thomas

doi:10.1080/00365513.2021.1946844

Cited by 5 publications

(4 citation statements)

References 11 publications

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“…Although studies have shown that samples for DOAC monitoring with functional coagulation assays can be stored for 24 hours at room temperature before testing without loss of stability, 22 in vitro stability of DOACs stored at room temperature is significantly longer. 13 Direct measurement of DOAC concentration in plasma samples by chromatographic methods may, therefore, be necessary for monitoring treatment with DOACs outside the hospital setting when such quantification is indicated.…”

Section: Discussionmentioning

confidence: 99%

Serum or Plasma for Quantification of Direct Oral Anticoagulants?

Aakerøy

Stokes

Marija

et al. 2022

Therapeutic Drug Monitoring

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Background: Direct oral anticoagulants are increasingly replacing vitamin K antagonists for prevention of stroke in patients with atrial fibrillation, partly owing to the lack of a need for routine monitoring. Therapeutic drug monitoring may still be warranted under certain circumstances. It is generally assumed that serum and plasma can be interchangeably used for this purpose. The aim of this study was to investigate possible differences between the serum, citrate-plasma, and ethylenediaminetetraacetic acid (EDTA)-plasma concentrations of apixaban and rivaroxaban in a larger patient group and their relation to factor X measurements.Methods: Plasma and serum samples were drawn during the same venipuncture from patients treated with apixaban or rivaroxaban. Drug levels were measured using ultrahigh-performance liquid chromatography combined with tandem mass spectrometry. Three sample matrices were obtained from 8 healthy volunteers for measurement of factor X antigen and activity.Results: Mean concentrations of apixaban and rivaroxaban were 16.8% and 36.6% higher in serum than in citrate-plasma, respectively (both P , 0.001). The corresponding differences in serum versus EDTA-plasma were 4.5% for apixaban and 13.1% for rivar-oxaban (both P , 0.001). Factor X antigen measurements in citrateplasma, EDTA-plasma, serum with clot activator, and serum without additives yielded comparable results, and factor X activity was significantly higher in serum than in plasma.Conclusions: Apixaban and rivaroxaban concentrations were significantly higher in serum than in plasma. The difference was more pronounced with rivaroxaban and was larger between serum and citrate-plasma than between serum and EDTA-plasma. Higher factor X activity in serum may explain the observed concentration differences. The choice of matrix is, thus, important when interpreting therapeutic drug monitoring results and in research involving analyses of direct oral anticoagulants. The authors recommend citrate-plasma as the preferred matrix.

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Section: Discussionmentioning

confidence: 99%

Serum or Plasma for Quantification of Direct Oral Anticoagulants?

Aakerøy

Stokes

Marija

et al. 2022

Therapeutic Drug Monitoring

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“…Compared with the other studies investigating the stability of DOAC in whole blood patient samples, 9 12 the main strengths of our studies were: the coverage of a wider range of anti-Xa activities; the measurement of these activities with two different commercial reagents in two different laboratories; the inclusion of a larger number of samples; and, finally, a more stringent acceptability range (± 15% instead of ± 20%), consistent with international guidelines. 7 We chose not to investigate DOAC stability over 6 hours, as in routine practice all samples can be analyzed within this delay.…”

Section: Discussionmentioning

confidence: 94%

Stability of Rivaroxaban and Apixaban Anti-Xa Activities in Whole Blood Samples: A French Bicentric Study

et al. 2023

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“…Nonetheless, studies that are directed to determine intra- and inter-individual variation for DOACs are lacking, as is common for almost all drugs. Based on the study by Reda et al, inter-individual biological variations for various DOACs exceed 40% at peak and 60% at trough concentrations and intra-individual CV above 20%, so the acceptable CV was set at 20% even though the analytical CV was below 10% [ 30 , 31 , 33 ]. It is essential to take into consideration that the lower concentrations had higher deviations from baseline values in percentages, but clinically, this was not significant, e.g., the sample’s baseline value was 24 ng/mL with 37.5% deviations on the third day, which meant 33 ng/mL ( Table 2 and Table 3 ).…”

Section: Discussionmentioning

confidence: 99%

“…All of the statistical tests were two-sided using a significance level of 0.05. Acceptable stability was defined as 80–120% of the baseline result, and any deviation greater than 20% was considered clinically significant [ 30 , 31 , 32 ].…”

Section: Methodsmentioning

confidence: 99%

Stability of Direct Oral Anticoagulants Concentrations in Blood Samples for Accessibility Expansion of Chromogenic Assays

et al. 2023

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Background and Objectives: Direct oral anticoagulants (DOACs) are used for minimising the risk of thromboembolic events. In clinical practice, there is no need to measure DOAC concentration in the routine. Nevertheless, there are cases where such measurements are necessary, as the European Society of Cardiology’s guideline recommends. However, determining DOAC levels is not available for everyone due to chromogenic assay availability limitations from sample storage problems, as tests are performed only in a few healthcare settings. This study aimed to assess whether more applicable storage conditions could be used for transportation to provide chromogenic assays for outpatient healthcare and other hospitals’ practices. Materials and Methods: Chromogenic assays measuring anti-FXa (for rivaroxaban and edoxaban) and anti-FIIa (for dabigatran) were used. Concentrations were determined immediately after blood collection as baseline value: (1) after the storage of citrated whole blood in refrigerator (+2–8 °C); (2) of citrated plasma in refrigerator (+2–8 °C); and (3) of citrated frozen plasma (−20 °C) on the third and seventh days of storage. Acceptable change limits were considered stable if the deviation did not exceed ±20% of the baseline value. Results: The median (Cl 95%) baseline value of rivaroxaban was 168 (147–236) ng/mL; of dabigatran 139 (99–178) ng/mL; and of edoxaban—174 (135–259) ng/mL. The median deviation from a baseline value stored as citrate whole blood samples (+2–8 °C) was 5.4% and 3.4%; as citrated plasma (+2–8 °C) was 0.4% and −0.6%; and as citrated frozen plasma (−20 °C) was −0.2% and 0.2% on the third and seventh days of storage, respectively. Conclusions: Our data suggest that whole blood samples stored in a refrigerator, as well as citrated plasma samples stored in both the refrigerator and freezer, preserve DOAC concentration stable at +2–8 °C or −20 °C for up to 7 days, and are suitable for transportation, except for low-concentration samples.

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Evaluation of the in vitro stability of direct oral anticoagulants in blood samples under different storage conditions

Cited by 5 publications

References 11 publications

Serum or Plasma for Quantification of Direct Oral Anticoagulants?

Serum or Plasma for Quantification of Direct Oral Anticoagulants?

Stability of Rivaroxaban and Apixaban Anti-Xa Activities in Whole Blood Samples: A French Bicentric Study

Stability of Direct Oral Anticoagulants Concentrations in Blood Samples for Accessibility Expansion of Chromogenic Assays

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