Unfractionated heparin inhibits thrombin (IIa) by binding to which molecule?

• A. Antithrombin III
• B. Plasmin
• C. Factor Xa
• D. Protein C

Answer: (A)

Unfractionated heparin exerts its anticoagulant effect by binding to antithrombin III, a serine protease inhibitor. This binding greatly accelerates AT-III’s ability to inactivate thrombin (IIa) and other proteases. For thrombin inhibition, the long chains of unfractionated heparin allow formation of a complex where AT-III binds thrombin and suppresses its activity. That’s why the molecule heparin targets to block thrombin is antithrombin III. In contrast, low molecular weight heparin relies more on AT-III to inhibit Factor Xa and is less effective at inhibiting thrombin because of its shorter chain length. Plasmin, Protein C, and Factor Xa are involved in related pathways, but the direct binding partner through which unfractionated heparin inhibits thrombin is antithrombin III.