**2.2 Anticoagulants and the mechanisms of action**

Generally, anticoagulants exert their effects at different points of the coagulation cascade. Certain anticoagulants function directly as enzyme inhibitors, while some

act indirectly by binding to antithrombin (AT) or inhibiting their production in the liver, such as vitamin K-dependent factors (**Figure 2**) [12].

## *2.2.1 The mode of actions of the common anticoagulants*

## I.Vitamin K dependent anticoagulant

Coumarin and its derivatives are a class of vitamin K–dependent anticoagulants (VKAs). Warfarin is the most common anticoagulant agent currently in use. It functions to inhibit vitamin K epoxide reductase (VKOR), which is necessarily required for the gamma-carboxylation of vitamin K-dependent factor, including factors II, VII, IX, X and protein C and S. Inhibition of vitamin K carboxylation triggers the decreased hepatic synthesis activity of clotting factors, leading to an anticoagulated state. Bleeding is the most common complication associated with warfarin therapy and is related to exponentially higher international normalised ratio (INR) values. The goal of the management is to reduce the INR back to a therapeutic safe level and hence are monitored by the value of the INR [13]. The dose-effect is narrow, and its actions are altered intensely by some factors, such as vegetables, greenleaf, some certain fruits, some drugs while inherited mutations in the VKOR complex may lead to resistance [12].
