platelet aggregation inhibition

Thromboxane A2 (TXA2) produced by activated platelets stimulates activation of new platelets and increases platelet aggregation by mediating expression of GP IIb/IIIa in the cell membrane of platelets.

Circulating fibrinogen binds to GP IIb/IIIa receptors causing aggregation.

Thrombin converts fibrinogen to fibrin which is cross linked by factor XIII to form a clot.

Aspirin inhibits prostaglandin formation which leads to TXA2 inhibition.

Clopidrogel which is a prodrug activated by CYP2C19 irreversitly inhibits P2Y12 and ADP receptors which blocks the activation of GP IIb/IIIa receptors to bind with fibrinogen.

cAMP inhibits platelet activation by decreasing cytosolic levels of calcium and, by doing so, inhibits the release of granules that would lead to activation of additional platelets and the coagulation cascade.

vitamin K cycle

The vitamin K cycle is essential for post-translational gamma-carboxylation of several blood coagulation factors and, therefore, coagulation. (VKORC1: vitamin K epoxide reductase complex 1, CYP2C9: cytochrome P450, family 2, subfamily C, polypeptide 9)

Cardiovascular pharmacogenomics and individualized drug therapy

Nature Reviews Cardiology 2009

Rivaroxaban

Rivaroxaban- oral direct Xa inhibitor

Rivaroxaban versus Warfarin in Nonvalvular Atrial Fibrilation
N Engl J Med 2011

Non inferiority trial

In July 2011, FDA approved rivaroxaban (Xarelto) for prevention of deep vein thrombosis in patients undergoing knee or hip replacement surgery.