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Impact of Non-Vitamin K Antagonist Oral Anticoagulants From a Basic Science Perspective.

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Published:1st Oct 2017
Author: Hoffman M, Monroe DM.
Availability: Free full text
Ref.:Arterioscler Thromb Vasc Biol. 2017;37(10):1812-1818.
DOI:10.1161/ATVBAHA.117.306995

The biochemical properties of the NOACs and their differences from the mechanism of action of VKAs contribute to their properties as anticoagulants. These properties include:

1. Inhibiting a single protease is much less “effective” at inhibiting coagulation than is inhibiting at multiple steps. Thus, the dose-response relationship between NOAC level and intensity of anti-coagulation is shallower and more linear than that of vitamin K antagonists. This partially accounts for the greater safety of NOACs than VKAs reported in some studies.
2. Since they are small molecules, NOACs can reach their target proteases in locations that plasma protease inhibitors, such as antithrombin, cannot.
3. NOACs compete with substrates for binding at the active site of the target protease, and that binding is reversible. When the drug level falls, the drug dissociates from its target and protease activity is restored. Thus, there is the possibility of a “rebound” in procoagulant activity if the drug is abruptly terminated.
4. The effects of a NOAC can be overcome by increasing the amount of substrate available for the target protease or the amount of protease produced. This property may contribute to the safety of NOACs and their potential reversibility by coagulation factor concentrates.

The biochemical properties of NOACs contribute to their suitability for use in conditions that require a predictable moderate degree of anti-coagulation when administered orally at a consistent dose. Their effects can be overcome by a sufficiently strong procoagulant stimulus. This characteristic likely contributes to their generally reduced risk of serious bleeding. However, they are not well suited for use in settings that require a profound degree of anticoagulation.

 

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