Antiplatelet therapy in surgery

Question 1

Drugs used in DAPT following coronary artery stenting?

Answer 1

Aspirin and clopidogrel

Question 2

What drug class is clopidogrel?

Answer 2

A thienopyridine - P2Y12 receptor antagonist. Prevents platelet activation and aggregation.

Question 3

What drug class is aspirin?

Answer 3

NSAID - COX inhibitor which prevents the formation of thromboxane via the arachidonic acid pathway. This prevents platelet activation and aggregation.

Question 4

Normal platelet count? When is it too low for surgery?

Answer 4

150,000 - 450,000 is normal.
Less than 50,000 per uL would be a concern for surgery. Spontaneous bleeding occurs when less than 10,000. Above 50,000 usually okay for surgery.

Question 5

Name 3 surgeries with a high risk of bleeding:

Answer 5

Heart valve replacement
Coronary artery bypass
AAA repair
Bilateral knee replacement
TURP

Question 6

Name some platelet activating factors

Answer 6

ADP, 5-HT, thrombin, thromboxane A2

Question 7

Describe the steps involved in platelet plug formation.

Answer 7

How platelets work to decrease bleeding after vascular injury:

1. platelet adhesion
   
   1. platelet surface receptors bind to collagen in the subendothelium. Also bind to vWF via platelet GpIb receptor. Platelets change shape and release mediating factors.
2. platelet binding and change in shape releases platelet activating factors including thrombin, ADP, 5HT, and thromboxane A2. Causes platelet activation to occur.
3. platelet aggregation → platelets clump together
4. formation of a platelet plug (primary haemostasis)
5. procoagulant activity → enzyme complexes of the clotting cascade occur on the surface of platelets

*Note that GPIIb/IIIa receptor inhibitors such as eptifibatide and tirofiban are used in acute coronary syndromes in high risk patients to prevent platelet aggregation and clumping.

Question 8

What is the half life of aspirin and how many days does aspirin need to be ceased prior to surgery?

Answer 8

1/2 of aspirin is ~6hrs
Aspirin irreversibly inhibits COX1 pathway in platelets. This means we need to wait the lifespan of the platelets. Hence, achieve safe levels of normally functioning platelets 5-7days prior to surgery.

Question 9

Describe protocol for ‘bridging’ of anti-coagulant (in the case of long term warfarin use)

Answer 9

With hold warfarin from 5 days prior to surgery (i.e. take last dose 6days prior to surgery). Commence taking enoxaparin 4 days prior to surgery when the INR is 2 or less.
Cease enoxaparin 24hrs prior to surgery. INR needs to be less than 1.5 at the time of surgery.

Question 10

Describe a ‘points’ method for assessing a patient’s risk of stroke?

Answer 10

CHA2DS2-VASc
1 point for each:
- CCH
- HTN
- Age 75+ (2 points) 65-74yrs (1 point)
- diabetes
- Previous stroke (2 points)

• Vascular disease
• age over 65yrs
• sex (female)

Question 11

Why is warfarin difficult to prescribe and use?

Answer 11

• narrow therapeutic band → requires monitoring
• drug interactions → warfarin is protein bound and only the free proportion is active. Drugs that are also protein bound may displace the warfarin and increase its effect e.g. antibiotic (like doxycycline), amiodarone (used for rate control in AF), allopurinol, tamoxifen, digoxin, frusemide, statins
• high risk of bleeding
• crosses the placenta → can cause CNS abnormality and foetal bleeding/pregnancy loss. NOT excreted in breast milk
• MOA: blocks hepatic production of Vit, K dependent coagulaiton proteins