Does Eliquis (apixaban) affect protein C levels?

From the Guidelines

Eliquis (apixaban) does not directly affect protein C levels in the body. Eliquis works by inhibiting factor Xa, which is a different part of the coagulation cascade than protein C. Unlike warfarin, which can reduce protein C levels and potentially cause a transient hypercoagulable state when therapy is initiated, Eliquis does not interfere with the vitamin K-dependent synthesis of protein C, as supported by the most recent guidelines 1, 2. This is one of the advantages of direct oral anticoagulants (DOACs) like Eliquis over vitamin K antagonists. Some key points to consider when using Eliquis include:

• Metabolism: Eliquis is metabolized by CYP3A4, with minimal involvement of other CYP enzymes 1.
• Excretion: Eliquis is primarily excreted via the biliary and intestinal routes, with 27% excreted renally 1.
• Half-life: The half-life of Eliquis is approximately 12 hours 1. Patients with protein C deficiency or those concerned about protein C levels can generally take Eliquis without worrying about it worsening their protein C status. However, if you have a specific clotting disorder related to protein C deficiency, you should discuss your anticoagulation options with your healthcare provider, as individual medical circumstances may vary. Regular monitoring of your overall coagulation status may still be necessary depending on your specific medical condition.

From the Research

Effect of Eliquis on Protein C Levels

• The effect of apixaban (Eliquis) on protein C levels is not directly stated in most studies, but some provide insight into its interaction with coagulation assays and proteins.
• A study published in 2014 3 investigated the effects of apixaban on common coagulation methods and found that apixaban showed fewer effects in vitro than rivaroxaban, another direct FXa inhibitor.
• The study also found that the effects of apixaban on antithrombin, protein C, and protein S assays were dependent on the type of reagent used.
• A case series and review of literature published in 2022 4 reported the clinical outcomes of using apixaban in patients with systemic thrombosis caused by protein C or S deficiency and found that apixaban could be effective in preventing recurrent thrombotic events in patients with inherited thrombophilia without safety concerns.
• However, the study also noted that one patient developed recurrent thrombotic events despite switching to a different type of DOAC and was ultimately transitioned back to warfarin.

Interaction with Coagulation Assays

• Apixaban has been found to affect coagulation assays, including activated partial thromboplastin time (APTT) and prothrombin time (PT) 3.
• The study found that the concentration of apixaban needed to double the APTT varied between 2200 and 4700 μg/L, and the concentration needed to double the PT varied between 700 and 3900 μg/L.
• The effects of apixaban on antithrombin, protein C, and protein S assays were dependent on the type of reagent used, and chromogenic anti-FXa assays showed linear dose-response curves with apixaban 3.

Clinical Implications

• The use of apixaban in patients with protein C and S deficiency has been reported in a case series and review of literature 4.
• The study found that apixaban could be effective in preventing recurrent thrombotic events in patients with inherited thrombophilia without safety concerns, but further large studies are warranted to investigate the safety and efficacy of apixaban in these populations.