109Accuracy of test results for Direct Oral Anticoagulants (DOACs) and Warfarin- importance of External Quality Assessment (EQA)

Abstract

Introduction: Lifelong anticoagulation is widely used in atrial fibrillation (AF) and anticoagulation with warfarin therapy is effective in stroke prevention in AF patients. The introduction of Direct Oral Anticoagulants (DOACS) has increased choice in anticoagulant control. However one concern with DOACs is the measurement of these drugs. It has been established in clinical trials that these drugs are non inferior or superior to warfarin therapy without the need to monitor but in some circumstances we still need to be able to measure the concentrations and effects of these drugs. Methods: The UK National External Quality Assessment Service for Blood Coagulation (UK NEQASBC) has provided proficiency testing for INR in the laboratory and Point of Care (POC) settings for over 20 years . The introduction of DOAC therapy has led to laboratories using specific assays to measure the inhibition of FXa or FIIa during this therapy. UK NEQAS BC has distributed samples containing DOACS to>800 laboratories and compared the results obtained in screening tests with widely available reagents. We have also introduced a DOAC assay EQAprogramme which currently has 120 centres enrolled. Results: Laboratory INR monitoring shows good inter-laboratory precision with an annual average CV of 5.6%. POC INR testing EQA shows an annual average CV of 6.5% for the most widely used hand held device. These data show that the INR system of standardisation of reagents is working well and the ideal that the same patient would obtain the same INR result wherever that test was performed can largely be achieved for stabilised patients although EQA has identified clinically relevant errors in INR measurements in some centres. Our data show routine coagulation screening tests are not reliable for assessing DOAC concentration as different reagents can show difference prolongation of the tests. DOAC assays are becoming more available and Assays of Dabigatran, Rivaroxaban, and Apixaban are available and several different methods for each are employed, with edoxaban assays recently launched. In a recent survey with 2 samples tested for Dabigatran, 2 for Rivaroxaban and 2 for Apixaban CVs ranged from 10%-16% showing reasonable between laboratory precision. For one sample however containing no Apixaban 22 centres reported results of 0ng/ml, 20 reported less than their lowest measuring range which varies from 10 to 30ng/ml, but 2 centres reported results of 36.8 and 41ng/ml. Conclusion: EQA for INR testing shows good agreement between methods both in the laboratory setting and the POC settings. Screening tests for DOAC may be useful whereby a prolonged prothrombin time (PT) or activated partial thromboplastin time (APTT) may indicate the presence of DOAC but a normal PT or APTT does not exclude their presence. Accurate assays to assess DOAC concentrations are required when measurement is needed.