Unveiling the complex effects of direct oral anticoagulants on dilute Russell's viper venom time assays

Introduction Dilute Russell viper venom time (dRVVT) assays can be affected by direct oral anticoagulants (DOACs), which may cause false-positive results. However, there are conflicting results indicating significant differences between different reagents and DOACs. Objectives To evaluate the effect of DOACs on dRVVT assays. Material and Methods Samples were prepared by adding DOAC (dabigatran, rivaroxaban, apixaban, or edoxaban) to pooled normal plasma in the concentration range 0 to 800 mu g/L. Six integrated dRVVT reagents were used, all composed of a screen assay (low phospholipid content) and a confirm assay (high phospholipid content). The screen/confirm dRVVT results were expressed as normalized ratios. To further evaluate the observed differences between tests and DOACs, addition of synthetic phospholipids was used. Results The dRVVT ratios increased dose dependently for all DOACs, with four of the six tests and the DOAC rivaroxaban having the greatest effect. With one test, the ratios were almost unaffected with increasing DOAC concentration, whereas another test revealed a negative dose dependency for all DOACs. Variable DOAC effects can be explained by different effects on dRVVT screen and confirm clotting time. Adding synthetic phospholipids to samples containing rivaroxaban resulted in greatly reduced screen clotting times and thereby lower calculated dRVVT ratios. Conclusions There is a great variability in the dRVVT test result with different DOACs. The dRVVT ratios are unaffected for some reagents and this can be explained by an equal dose-dependent effect on both screen and confirm assays. The phospholipid type and content of the different reagents may contribute to the observed differences.