Therapeutics of Cardiovascular Diseases

Thrombosis and Haemostasis

2008

Dr. George Hsiao

Principles of haemostasis

The three stages invoved in haemostasis are blood vessel constriction, formation of a platelet plug, and formation of a clot.

Coagulation vs Platelet

Thrombosis Thrombosis is the pathological formation of a

clot known as a thrombus. Arterial occlusion, which may lead to

myocardial infarction, stroke, and peripheral ischemia.

Venous occlusion, which may lead to deep venous thrombosis and pulmonary embolism.

AnticoagulantsVitamin K antagonists Warfarin, acenocoumarol (nicoumalone), and phenindione

are examples of vitamin K antagonists. Mechanism of action: Vitamin K antagonists block the

reduction of vitamin K epoxide, which is necessary for its action as a cofactor in the synthesis of factors II, VII, IX, and X.

Heparin and the low-molecular weight heparins Mechanism of action: Heparin activates antithrombin III,

which limits blood clotting by inactivating thrombin and factor X. Heparin also inhibits platelet aggregation, possibly as a result of inhibiting thrombin. Low-molecular weight heparins are simply fragments of heparin which exhibit very similar activity to heparin.

Hirudins Mechanism of action: Derived from the medical leech,

hirudin, or rather its recombinant derivatives, desirudin and lepirudin, inactivate thrombin.