Heparin Mechanism of Action
The correct answer is A: Heparin binds to antithrombin III (AT-III) and inactivates thrombin and serine proteases. 1, 2
Primary Mechanism
Heparin functions by binding to antithrombin III through a specific pentasaccharide sequence, which induces a conformational change that converts AT-III from a slow to a very rapid inhibitor of coagulation enzymes. 1, 3 This represents the fundamental mechanism by which heparin exerts its anticoagulant effect.
The heparin-AT-III complex then inactivates multiple serine proteases in the coagulation cascade, including:
- Thrombin (Factor IIa) - the most sensitive target, approximately 10-fold more responsive than Factor Xa 1, 3
- Factor Xa 1, 2
- Factor IXa 1
- Factor XIa 1
- Factor XIIa 1
Why the Other Options Are Incorrect
Option B is incorrect: Heparin does not bind to or inactivate plasmin. 2 Plasmin is a fibrinolytic enzyme, and heparin has no fibrinolytic activity—it cannot lyse existing clots. 2
Option C is incorrect: Heparin does not lyse the Activated Protein C/S complex. 2 In fact, by inactivating thrombin, heparin actually inhibits thrombin-induced activation of Factor V and Factor VIII, which are substrates for Protein C. 1
Option D is incorrect: Heparin does not lyse Factor V and Factor VIII. 1 Rather, by inhibiting thrombin, heparin prevents the thrombin-induced activation of these factors, but this is inhibition of activation, not lysis. 1
Important Molecular Details
Only approximately one-third of administered heparin molecules contain the specific high-affinity pentasaccharide sequence required to bind AT-III and produce anticoagulant effects. 1, 3 The remaining two-thirds has minimal anticoagulant activity at therapeutic concentrations. 1
For thrombin inhibition specifically, heparin molecules must contain at least 18 saccharide units to bind simultaneously to both thrombin and AT-III. 1, 3 Smaller heparin fragments can still catalyze Factor Xa inhibition through AT-III binding alone. 1
Clinical Relevance
After the heparin-AT-III complex inactivates the target serine protease, heparin dissociates from the complex and can be reutilized, making it a catalytic process. 1 This mechanism explains why heparin is effective at preventing clot formation but cannot dissolve existing clots—it has no fibrinolytic activity. 2