Apixiban (Eliquis) and Rivaroxaban (Xarelto) are oral direct Factor Xa inhibitors. The laboratory has noticed an increasing incidence of orders for coagulation and thrombophilia tests, without notification that a patient is receiving one of these anticoagulants. Failure to provide this medication history can result in the reporting of erroneous results that may be misinterpreted. Also, the laboratory spends a lot of time investigating discrepant results and patients may be billed for meaningless tests.

Routine coagulation tests consist of prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen. PT may be prolonged by therapeutic levels of rivaroxaban, but is not affected by apixiban. INR is not a reliable indicator of the anticoagulant effect of Factor Xa inhibitors because the International Sensitivity Index (ISI) has been established for vitamin K antagonist (VKA) therapy and does not reflect sensitivity towards apixiban or rivaroxaban. APTT is elevated by rivaroxaban more than apixiban. Measurement of fibrinogen is not affected by these drugs. Likewise, thrombin time is not affected.

Heparin levels are measured by anti-factor Xa activity. Direct Factor Xa inhibitors prolong these assays and interfere with heparin measurement. If a patient who is taking one of these drugs is started on heparin therapy, anti-factor Xa activity will reflect the combination of heparin and the Factor Xa inhibitor. The reported heparin concentration will be erroneously high.

Thrombophilia testing includes activated Protein C resistance (APC), Factor V Leiden (FVL), prothrombin gene mutation (PGM), protein C activity, protein S activity, antithrombin, and lupus anticoagulant. APC is a screening test for FVL. Both apixiban and rivaroxaban factitiously increase the APC ratio, leading to falsely normal results. In this situation, the specimen would not be reflexed for FVL mutation analysis and the most common inherited cause of thrombosis would be missed. Genetic tests for FVL and PGM are not affected by FXa inhibitors. Antithrombin and Protein C are chromogenic assays that are not affected, but Protein S activity is a clot based assay that is factitiously overestimated.

Tests for lupus anticoagulant include aPTT with mixing studies, hexagonal phase phospholipid neutralization test, and dilute Russell's viper venom test (DRVVT). As mentioned above, aPTT is variably prolonged by Factor Xa inhibitors. Mixing studies in patients receiving these drugs may not correct, producing a falsely positive mixing study. This falsely positive result leads to a cascade of additional testing for lupus anticoagulant. The hexagonal phase phospholipid neutralization test is based on the aPTT. Therefore, Factor Xa inhibitors may cause false positive results. DRVVT activates Factor X to initiate the common coagulation pathway. Factor Xa inhibitors can produce false positive results. Immunoassays for anticardiolipin antibodies and anti-beta2-glycoprotein1 antibodies are not affected.

This summary pertains to specimens tested on Stago coagulation instruments and reagents. Results obtained in other laboratories using different products may differ.