Anticoagulation Pharmacology

Question 1

Describe the coagulation pathway?

Answer 1

Intrinsic dmg surface:
- XII => XIIa
- XI => XIa
- IX => IXa
- X => Xa
- Prothrombin -> thrombin
- Fibrinogen -> fibrin.
- XIIIa
- Cross - linked fibrin clot.

Question 2

What is the role of thrombin?

Answer 2

Thrombin cleaves fibrinogen, producing fragments that polymerise to form insoluble fibrin.
Activated factor XIII - strengthens fibrin links.
Platelet aggregation
Cell proliferation

Question 3

What is the MOA of heparins?

Answer 3

Inactivates antithrombin III
- Inactivates thrombin & Xa & other SER proteases.
- Changes conformation of ATIII
- Accelerates rate of action of ATIII
–| A single molecule of Xa helps prevent the formation of hundreds of thrombin molecules.

Question 4

What is unfractionated heparin?

Answer 4

–| both thrombin & Xa, however, LMWH –| mainly Xa & therefore its effects are predictable.
Unfractionated heparin is only used in hospitals

Question 5

What are the advantages of LMWH?

Answer 5

• Binds less to endothelium & plasma proteins.
• Predictable dose response.
• Decrease frequency of dosing.
• Less S/E
• Can be used at home.

Question 6

How does Vitamin K work?

Answer 6

–| hepatic vit K dependent synthesis of factors II, VII, IX & X & of anticoag protein C & its cofactor protein S
Since warfarin acts indirectly, has no effect on existing clots.
Takes at least 48-72hrs to achieve antithrombotic effect