Novel oral anticoagulants (rivaroxaban, apixiban and dabigatran) have been approved by FDA for reducing the risk of stroke in patients with nonvalvular atrial fibrillation and prevention of deep vein thrombosis. The common mechanism of these new drugs is reversible blockage of the active enzyme site of thrombin (Factor IIa) or Factor Xa.
All of the new oral anticoagulants (NOAC) are given at fixed doses and do not require routine coagulation monitoring because of their predictable pharmacokinetics. These drugs variably prolong prothrombin time and activated plasma thromboplastin time. However, these routine clotting tests cannot be used to accurately assess the anticoagulant effect of NOAC. Even more problematic for the clinical laboratory is their interference with special coagulation testing.
The direct anti-FXa inhibitors (apixiban and rivaroxaban) have the following effects on special coagulation tests:
- Coagulation factor levels - artifactually reduced factor levels
- Bethesda assay - falsely positive
- DRVVT - falsely positive
- Activated Protein C resistance (APC-R) - falsely normal ratio
- AT activity (Xa based) - over estimated
- AT activity (IIa based) - no effect
- Protein C activity (clot based) - falsely over estimated
- Protein C activity (chromogenic) - no effect
- Protein S activity (clot based) - falsely over estimated
The direct anti-Factor IIa inhibitor (dabigatran) affects the following specialized coagulation tests:
- Thrombin time - prolonged
- DRVVT -falsely positive
- Factor levels - artifactually reduced factor levels
- Factor inhibitor - falsely positive Bethesda assay
- Activated Protein C Resistance - falsely normal ratio
- AT activity (Xa based) - no effect
- AT activity (IIa based) - over-estimated
- Protein C activity (clot based) - falsely elevated
- Protein C activity (Chromogenic) - no effect
- Protein S activity (clot based) - falsely elevated
Clinical laboratories can waste a lot of time working up abnormal results and may even report erroneous results if clinicians do not provide the laboratory with an accurate drug history.