Edoxaban: Impact on routine and specific coagulation assays. A practical laboratory guide

Area of Science:

• Pharmacology
• Clinical Chemistry
• Hematology

Background:

• Assessing edoxaban's plasma concentration and effect is crucial in certain clinical scenarios.
• Understanding how routine coagulation assays are influenced by edoxaban is essential for accurate interpretation.
• Standardized methods are needed to evaluate edoxaban's pharmacodynamics and its impact on hemostasis diagnostics.

Purpose of the Study:

• To identify coagulation tests suitable for assessing edoxaban's pharmacodynamics.
• To provide guidance on interpreting hemostasis diagnostic tests in the presence of edoxaban.
• To evaluate the influence of edoxaban on various coagulation assays and reagents.

Main Methods:

• Edoxaban was spiked into platelet-poor plasma across a range of therapeutic concentrations (0-1,000 ng/ml).
• Multiple coagulation assays were performed, including aPTT, PT, dRVVT, chromogenic anti-Xa, and TGA, using various reagents.
• The impact of edoxaban on lupus anticoagulant, protein S, APC-R, antithrombin, and clotting factor activity was assessed.

Main Results:

• A concentration-dependent prolongation of aPTT, PT, and dRVVT was observed, with reagent-dependent variations.
• Chromogenic anti-Xa assays demonstrated high sensitivity and linear correlation with edoxaban concentration.
• Edoxaban interfered with assays for lupus anticoagulant, protein S, APC-R, antithrombin, and clotting factor activity, but not with immunological assays.

Conclusions:

• Some PT reagents may estimate edoxaban activity, but chromogenic anti-Xa assays are necessary for accurate plasma concentration assessment.
• Thromboelastography (TGA) shows potential for pharmacodynamic assessment but requires standardization.
• For thrombophilia or bleeding event investigations, immunological assays are recommended when applicable; standardized sampling times are mandatory.