International external quality assessment for measurements of direct oral anticoagulants: results and recommendations

Abstract

There is limited information regarding the performance of tests for direct oral anticoagulants (DOACs). To generate more knowledge, the accuracy of DOAC tests were evaluated using external quality assessment data from multiple years. This data demonstrated a good correlation for the tests with a small overall interlaboratory variability (10% for dabigatran, rivaroxaban and apixaban and 12% for edoxaban). The greatest differences between the various reagents were observed for rivaroxaban, especially for concentrations below 100 ng/ml. In conclusion, the results show overall reliable DOAC levels with some differences between reagent groups. Important finding: clinical decision criteria could be affected by the choice of reagent.

2021 Update of the International Council for Standardization in Haematology Recommendations for Laboratory Measurement of Direct Oral Anticoagulants

“…Most international external quality control (EQA) programmes now have established EQA exercises for DOACs and demonstrate a wide implementation of specific DOAC testing in certain regions of the world. [111][112][113][114][115][116][117][118] Nevertheless, in regions where the regulatory authorities have refused the approval of these specific kits, access to drug measurements may be limited to specialized laboratories. In addition, only few undertake the in-house validation of these techniques refraining the clinicians to ask for these specific drug measurements.…”

“…6,119 Some international EQA programmes have also undertaken and published studies looking at DOAC interference in haemostasis tests. [111][112][113][114][115][116][117][118] Some have also undertaken studies looking at neutralizing the interference of DOACs in haemostasis tests. 120 Although differences were seen between the various methodologies, reliable and reproducible DOAC levels were measured overall.…”

“…Although no international calibration standards were available, the overall coefficients of variation (CVs) were small for dabigatran, rivaroxaban and apixaban, and were also comparable to the CVs (range: 3-14%) for the international normalized ratio derived from the same years. 113 The outcome for the various methodologies in the EQA surveys could be used to establish clinical decision rules adapted for specific reagents. This is especially relevant in the ranges approaching clinical decision limits.…”

Interlaboratory Performance in Measurement of Dabigatran and Rivaroxaban

“…Owing to the higher number of participants, they were able to evaluate the data per reagent group if more than 10 participants were present in the survey from 2017. 24 Another ECAT international dabigatran and rivaroxaban survey with a large number of international participants and a small percentage of North American laboratories (11 of 123) assessed the interlaboratory variation by using the same definition 14 and showed similar findings 25 : intermediate CV for the 2 most commonly used dabigatran assays (dTT, Hemoclot; and anti-IIa assay, Biophen DTI). Owing to the large number of participants, they were able to sort the data by reagents and calibrators.…”

“…The previously mentioned first ECAT study's lowest rivaroxaban concentration of 85 ng/mL had an overall CV of 13%, which differed significantly between different methodologies (up to 20% difference), with the lowest CV observed for Stago and HemosIL Liquid Anti-Xa assays. 24 The second ECAT study assessed 2 rivaroxaban concentrations (100 ng/mL and 300 ng/mL) and showed that 5 of the 6 most commonly used reagents had intermediate interlaboratory precision (11%-20%) for 100ng/mL drug concentration. 25 These results suggest that interlaboratory variability for dabigatran and rivaroxaban measurement could be improved.…”