S10.1 Anti-Platelet and Anticoagulant Therapy

Question 1

How can a thrombus form?

Answer 1

From activation of any of Virchow’s Triad (abnormality to vessel wall, abnormality to blood constituents, abnormality to blood flow).

Question 2

What is the mechanism of warfarin?

Answer 2

Inhibits production of vitamin K dependant clotting factors.
Vitamin K normally acts to carboxylate certain clotting factors

Question 3

Describe the pharmacokinetics of warfarin

Answer 3

Has a slow onset of action and a slow offset.
Heavily protein-bound so can be displaced to have greater effect.
Metabolism is via CYP450 metabolic pathway, so levels effected with liver disease or drugs which affect p450 system

Question 4

How do we monitor dose levels of warfarin?

Answer 4

Via INR - time taken for blood to clot, so high INR means poor blood clotting

Question 5

What are the uses of warfarin?

Answer 5

To get target INRs of 2.0-3.0 for DVT, PE, or AF.

Or INRs of 2.5-4.5 for mechanical prosthetic valves.

Question 6

What are the ADRs of warfarin?

Answer 6

GI haemorrhage
Epistaxis
Teratogenic

Question 7

What is used in reversal therapy for warfarin?

Answer 7

Vitamin K1

Question 8

What is the mechanism of heparin?

Answer 8

Glycosaminoglycan that acts on Anti-Thrombin III which deactivates Factor Xa and thrombin (IIa)

Question 9

What are the two types of heparin?

Answer 9

Unfractionated heparin (IV) – inhibits Xa and thrombin.
Low molecular weight heparin (subcutaneous) e.g. Dalteparin – inhibits Xa only.

Question 10

Name two direct Xa inhibitors

Answer 10

Fondaparinux

Apixaban

Question 11

Name two direct thrombin inhibitors

Answer 11

Argatroban

Dabigartran

Question 12

Describe the pharmacokinetics of heparin

Answer 12

Parenterally
Poor GI absorption, rapid onset and offset.
UH - needs APTT monitoring
LMWH - no APTT monitoring required

Question 13

What are the uses of heparin?

Answer 13

Prevents thromboembolism so used in DVT and PE.

Administered prior to Warfarin to cover patient whilst Warfarin loading is achieved as it has slow onset

Question 14

What are the ADRs of heparin?

Answer 14

Intracranial haemorrhage
Thrombocytopenia
Osteoporosis

Question 15

What is used in reversal therapy for heparin?

Answer 15

Protamine

This dissociates heparin from ATIII

Question 16

How do thromboxane A2 inhibitors work?

Answer 16

Thromboxane A2 is normally released from platelets to promote further platelet aggregation.

Question 17

How does aspirin work as a thromboxane A2 inhibitor?

Answer 17

Aspirin is a COX enzyme inhibitor so prevents thromboxane A2 production and thus prevents platelet aggregation

Question 18

How does dipyramidole work as a thromboxane A2 inhibitor?

Answer 18

Dipyridamole inhibits phosphodiesterase enzymes to inhibit thromboxane A2 production

Question 19

How do glycoprotein IIb/IIIa inhibitors work as a thromboxane A2 inhibitor?

Answer 19

Glycoprotein IIb/IIIa inhibitors decrease platelet crosslinking by fibrinogen.
Abciximab irreversibly binds to glycoprotein.
Tirofiban and eptifibatide reversibly bind.

Question 20

What are Platelet ADP-receptor antagonists?

Answer 20

Eg clopidogrel

These inhibit ADP dependant aggregation by inhibiting the ADP-receptor

Question 21

What are fibrinolytic agents (clot busters)

Answer 21

Eg streptokinase, alteplase

Agents which dissolve the fibrin meshwork of a thrombus.