W3 Antithrombotic and Fibrinolytics

Question 1

Function of..?
Anticoagulants
Anti-platelets
Fibrinolytics

Answer 1

• Prevent thrombus formation
• Prevent platelet aggregation
• Clot retraction

Question 2

What is Haemostasis?
What are the steps in this process?

Answer 2

Physiological process to stop bleeding (clot)
Positive feedback

1. Vascular spasm= pain reflux, constriction of vascular smooth muscle, trigger clotting chemicals/factors needed & directed to site of injury
2. Platelet activation-plug
   - Endothelial damage
   - Exposed collagen
3. Coagulation- Patch

Question 3

What is Von Willebrand factor?

Answer 3

Stabilises collagen. Glue for binding platelets into collagen cells
Von Willebrand factor acts as a bridge between collagen, exposed in damaged blood vessels, and the glycoprotein receptors, GPIIb/IIIa expressed in activated platelets

Question 4

3 ways that body undergoes clotting:

Answer 4

1. Thrombin mediated platelet activation
   - heparin released from endothelial cells
   - heparin recruits antithrombin
2. ADP mediated process
   - P2Y12
   - P2Y1 binds to ADP
3. Von Willebrand factor

Question 5

Fate of clot and vessel healing

Question 6

What are the examples of oral anticoagulants?

Answer 6

a) Vitamin K antagonist (VKAs)
=Warfarin
b) Direct oral anticoagulant (DOACs)
reversible factor Xa inhibitor
=Apixaban, edoxaban, rivaroxaban

reversible inhibitor of thrombin
=dabigatran

Question 7

Vitamin K antagonist (VKAs): Warfarin
What factors need to be activated by vitamin K?

Answer 7

Factors ll, Vll, IX and X need to be activated by vitamin K

Question 8

Properties of Warfarin

Answer 8

• Slow onset of action
• Inhibit Vitamin K-dependent protein C, natural anticoagulant and may cause pro-coagulant effects before exhibiting anti-coagulant effect.
• The vitamin K administration (in excess) can overcome warfarin binding to reductase enzyme (manage warfarin overdose with vitamin K)
• Pharmacokinetics: 99% bound to plasma albumin, Half-life 36 hours, metabolised in liver (CYPs) and
  eliminated in urine and stool.
• Drug interactions:
• Warfarin breakdown: Macrolide antibiotics, azole antifungal, H2 receptor antagonists
• NSAIDs potentiate the effect of warfarin
• Broad-spectrum antibiotics (kill gut flora and vit K synthesis) potentiate the effect of warfarin
• Adverse effects:
• Bleeding and skin necrosis

Question 9

How can Warfarin act as a pro-coagulant at first?

Answer 9

It blocks natural anticoagulants protein C and S and so anticoagulation stops occurring

Question 10

Heparin (unfractionated) & LMWHs (low molecular weight heparin)
Adverse effects

Answer 10

a) Haemorrhage
b) Heparin-induced thrombocytopenia
c) Hyperkalaemia

Inhibition of aldosterone secretion by unfractionated or low molecular weight heparin can result in hyperkalaemia;
patients with diabetes mellitus, chronic renal failure, acidosis, raised plasma potassium or those taking potassium-
sparing drugs seem to be more susceptible. The risk appears to increase with duration of therapy