Test - Biochemistry of Coagulation - Goueli

Question 1

What irreversibly inhibits platelet cycloxygenase 1?

Answer 1

Aspirin

Question 2

What is the mechanism of action of Aspirin?

Answer 2

Prevent platelets from generating Thromboxane A2 from COX1, inhibiting platelet aggregation for the lifetime of the platelet (8-9 days)

Question 3

What is the MOA of heparin?

Answer 3

Binds to and activates VTIII, which leads to thrombin inactivation

Question 4

What is the mechanism of action of coumadin (warfarin)?

Answer 4

Slow and long acting blood anticoagulant with a structure resembling that of Vitamin K, allowing it to compete with Vitamin K

• Blocks the vitK reductase enzymes used to regenerative active vitK
• Prevent gamma-carboxylation of glutamate residues in factors II, VII, IX, X, and proteins C and S
• Factors consequently cannot bind calcium and thus cannot bind to their phospholipid membrane sites of activation

Question 5

What does vWB do?

Answer 5

• Mediates adhesion of platelets to the collagen exposed on endothelial cell surfaces
• Acts as a bridge between GP Ib - GP V - GP IX complex on the surface of platelets and collagen fibrils
• Binds to and stabilizes coagulation factor VIII

Question 6

What is the primary reason a physician must “bridge with heparin” when starting a patient on Warfarin?

Answer 6

• Warfarin (Coumadin) also blocks the activity of proteins S and C
• loss of anticoagulant factors leads to increased risk of clotting initially