Anticoagulant mechanisms of warfarin/VKA and LMWH/UFH. Figure 1 provides a simplified representation of coagulation cascade showing targets of warfarin/VKA and LMWH/UFH. Warfarin/alternative VKA reduces synthesis of functional vitamin K–dependent coagulation factors; the mechanism is by competitive inhibition of vitamin K epoxide reductase enzyme, depleting functional vitamin K required for gamma-carboxylation of coagulation factors II, VII, IX, and X. LMWH/UFH potentiate the inhibition of factor Xa and thrombin (IIa), by antithrombin (AT), and also factors IXa and XIa. This prevents fibrin formation and inhibits thrombin- induced activation of platelets and factors V, VIII, XI, and XIII. Heparin binds to AT via a high-affinity pentasaccharide binding site. Maximal anti-IIa activity requires binding to AT and IIa simultaneously, with heparin acting as a bridge, and depends on a minimum heparin chain length (>18 saccharide units), unlike anti-Xa activity, which requires binding to AT only. LMWH, with its shorter average chain length, has lower anti-IIa activity than UFH, and its anticoagulant effect is predominantly from anti-Xa activity. Ca²⁺, calcium; PL, phospholipid; TF, tissue factor.