Antiplatelets

Antiplatelet agents are:

Indications

  • Arterial stenting

Contraindications

Enteral

Aspirin

Weak salicylic acid that causes irreversible COX-1 inhibition:

  • ↓ Thromboxane A2 production for the duration of platelet lifespan (5-10 days)

Key pharmacological properties:

  • Renally cleared
  • Half-life 1-2 hours

Clopidogrel

Thienopyridine that:

  • Causes irreversible P2Y12 ADP receptor inhibition
    Inhibits cAMP-dependent platelet activation for duration of platelet lifespan
  • Displays significant inter-individual variability
    15-50% of patients have impaired response to clopidogrel activity, which may be due to:
    • CYP450 polymorphism
    • Drug interaction
    • DM

Key pharmacological properties:

  • 50% renally, 50% biliary cleared
  • Half-life 1-2 hours

Ticagrelor

Adenosine analogue that:

  • Causes reversible P2Y12 ADP receptor inhibition
  • Has a similar mechanism of action to clopidogrel
  • More predictable inhibition than clopidogrel
  • ↑ Bleeding risk compared to clopidogrel

Key pharmacological properties:

  • Biliary elimination
  • Half-life 8 hours

Reversal

All enteral antiplatelet agents are minimally reversible, therapeutic options include:

  • Cessation
  • Other haemostatic measures
  • DDAVP
    May have effect in aspirin-induced platelet inhibition, minimal evidence in other contexts.
  • Platelet transfusions
    • More effective in aspirin
    • May be ineffective in reversing ticagrelor

DDAVP (desmopressin) is:

  • A synthetic vasopressin analogue
  • Dosed at 0.3μg/kg
    • Response is variable between patients, but usually consistent for the one patient
    • Tachyphylaxis occurs after 3-5 days
  • Used for a variety of pro-coagulant effects:
    • Release of stored vWF
      Effective for mild quantitative and some qualitative von Willebrand disease.
    • Release of factor VIII
      Effective for mild haemophilia A.
    • ↑ Platelet aggregation
      • ↑ Surface GP receptors
      • ↑ Platelet-dependent thrombin generation

Parenteral

Tirofiban

  • GP IIb/IIIa inhibitor
    Prevents platelet binding to fibrinogen and vWF.

Key pharmacological properties:

  • Intravenous administration
  • Renally cleared
  • Half-life 2 hours
  • Reversal in 4-8 hours following cessation

Eptifibatide

  • Indications:
    • High thrombus burden following STEMI/NSTEMI
    • Thrombotic complication of angiography
    • Bridging therapy prior to surgical revascularisation
  • Reversal in 4-8 hours following cessation

Abciximab

  • Reversal in 1-2 days following cessation

Complications

References

  1. Bersten, A. D., & Handy, J. M. (2018). Oh’s Intensive Care Manual. Elsevier Gezondheidszorg.