The effect of dabigatran and rivarovaban on a prothrombinase-based assay for activated protein C resistance: a preliminary study in subjects heterozygous for factor V Leiden.

Oral direct inhibitors of activated factor II (FIIa), such as dabigatran, and of activated factor X (FXa), such as rivaroxaban, have the potential to interfere with the great majority of clot-based coagulation assays and some chromogenic assays, whereas these drugs would not be expected to interfere in antigen-based assays1–4. Data concerning the influence of anti-FIIa and anti-FXa on functional assays for determination of activated protein C resistance (APCr) are still rather scarce and available studies have mainly been conducted using tests based on the activated partial thromboplastin time (aPTT). Moreover the data were obtained from in vitro studies performed on plasma from normal individuals, which was spiked with variable amounts of the drugs1–4. For dabigatran there is evidence that aPTT-based APCr methods over-estimate the APCr ratio, which may lead to patients with heterozygous factor V Leiden (FVL) being misclassified as normal1–4. In contrast, for rivaroxaban there is evidence that aPTT-based APCr methods may under-estimate the APCr ratio2,3. As previously reported, in our laboratory we adopted a prothrombinase-based method to study the APCr5. Data concerning the influence of dabigatran and rivaroxaban on this assay are still rather scarce. We, therefore, report the influence of FIIa and FXa direct oral inhibitors on the APCr, evaluated with a prothrombinase assay, in a small number of FVL patients.