Apixaban Interacts with Haemoglobin: Effects on Its Plasma Levels
Monica Sacco1, Stefano Lancellotti1, Federico Berruti1
1Institute of Internal Medicine & Geriatrics, Haemostasis and Thrombosis Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Area of Hematology, Catholic University of the Sacred Heart School of Medicine, Rome, Italy.
Thrombosis and Haemostasis
|September 21, 2018
Summary
Direct oral anticoagulant apixaban binds to hemoglobin, potentially affecting its plasma concentration. This interaction was confirmed through patient data, in vitro assays, and molecular simulations, suggesting hemoglobin acts as a drug buffer.
Area of Science:
- Pharmacology
- Biochemistry
- Hematology
Background:
- Direct oral anticoagulants (DOACs) like apixaban (APX) are crucial for preventing thrombosis.
- APX primarily binds to albumin, but its interaction with hemoglobin (Hb) remains unexplored.
- Understanding APX binding to Hb is vital for its pharmacokinetics and pharmacodynamics.
Purpose of the Study:
- To investigate the binding of apixaban to human hemoglobin.
- To determine if Hb influences APX plasma levels in patients.
- To elucidate the clinical implications of APX-Hb interaction.
Main Methods:
- Analysis of APX plasma levels and hematological parameters in 90 patients.
- Assessment of APX effect on Hb oxygen dissociation curves.
- In vitro binding assays (fluorescence spectroscopy, HPLC) and in silico molecular docking.
Main Results:
- Hemoglobin levels were inversely associated with APX peak plasma levels in patients.
- APX induced a left-shift in the Hb oxygen dissociation curve.
- Binding assays and molecular docking confirmed APX binds to Hb (Kd ≈ 300-350 µM).
Conclusions:
- Apixaban directly binds to hemoglobin.
- Hemoglobin may act as a buffer for APX, influencing its free plasma concentration.
- This interaction could impact APX pharmacokinetics and pharmacodynamics.
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