Anticoagulation

Question 1

What are anticoagulants?

Answer 1

Slow down clotting, reducing fibrin formation and prevents thrombus formation

Heparins, fondaparinux, dabigatran, warfarin, rivaroxaban, apixaban, edoxaban

Question 2

What are antiplatelets?

Answer 2

Prevent platelet aggregation and prevent thrombus formation when a blood vessel is damaged

Aspirin, clopidogrel, prasugrel, ticagrelor and dipyridamole

Question 3

Antiplatelet pharmacology

Answer 3

• Aspirin prevents COX-1 from converting arachidonic acid into prostaglandin H2 further progressing into thromboxane A2 and becoming TXA2
• Dipyridamole prevents phosphodiesterase from the conversion of cAMP into AMP reducing intracellular Ca2+ - causing vasodilation
• Clopidogrel, prasugrel and ticagrelor bind to P2Y12 receptor preventing ADP from binding
• Abciximab, tirofiban and eptifibatide prevents binding to glycoprotein IIb/IIIa preventing fibrin formation between the platelets

Question 4

The clotting cascade

Answer 4

Intrinsic:

12 - 12a
11 - 11a
9 - 9a and 13-13a
10 - 10a and 5-5a
Prothrombin - thrombin
fibrinogen - fibrin and 13-13a

Extrinsic:
7-7a and tissue factpr
10-10a

Question 5

Vitamin K antagonists

Answer 5

Warfarin, phenindione and acenocoumarin
Block the vitamin K dependent synthesis of clotting factors II, VII, IX and X
Take atleast 48-72 hours to take effect unless given with unfractionated or low mw heparin in which case effects are immediate

Question 6

Factor Xa inhibitors

Answer 6

Rivoroxaban, apixaban, edoxaban, fondaparinux

Question 7

Thrombin inhibitors

Answer 7

Dabigatran, argobatran

Question 8

Antiplatelet drugs

Answer 8

High blood pressure must be controlled before giving aspirin

Question 9

Which drug to give?

Answer 9

For AF, Pulmonary embolism or deep venous thromboembolism - Rivoroxaban, apixaban, edoxaban, dabigatran and warfarin

For mechanical heart valves: Warfarin

For long term stroke prevention not caused by AF or secondary prevention of ACS - Aspirin, clopidogrel

Question 10

Effects of anticoagulants

Answer 10

Increased risk of bleeding
Blood from GIT - May be dark or bright red mixed with stools, black stools, dizziness and dyspnea
Blood from brain (haemorrhage) - sudden onset of severe headache, loss of vision, slurred speech, trouble swallowing, loss of balance and sudden weakness of face, arm or leg on one side

Question 11

Ways to reduce risk of bleeding

Answer 11

1. Control BP
2. Stop aspirin when INR in therapeutic range
3. Review concominant use of NSAIDs, SSRIs and steroids
4. Consider a PPI

Question 12

Time in Therapeutic range (TTR)

Answer 12

Used to assess quality of anticoagulation with warfarin
Minimum > 65%
Patients with poorer TTR have more strokes and greater risk of bleeding and mortality