PharmacologyTier 1Medical Sciences concept

Antiplatelet and anticoagulant mechanisms of action

Core concept

Antiplatelet - four pathways

Aspirin - irreversible acetylation of COX-1 -> dec thromboxane A2 for the 10-day platelet lifespan
P2Y12 (ADP receptor) blockade
- Clopidogrel - thienopyridine prodrug, two-step CYP2C19 activation, irreversible, slowest and most variable onset
- Prasugrel - thienopyridine prodrug, single-step activation, irreversible, fastest onset and most potent
- Ticagrelor - not a prodrug, reversible, allosteric; twice daily; dyspnoea (adenosine reuptake inhibition), bradyarrhythmia
GPIIb/IIIa antagonists - abciximab, tirofiban, eptifibatide - block the final common pathway (fibrinogen crossbridging)
PDE inhibitors - dipyridamole, cilostazol

Anticoagulant

Heparin - binds antithrombin, inducing a conformational change that accelerates its inhibition of thrombin (IIa) and Xa ~1000-fold
- UFH - long enough to bridge AT to thrombin -> anti-IIa = anti-Xa
- LMWH - too short to bridge -> anti-Xa >> anti-IIa (~4:1)
- Fondaparinux - pure pentasaccharide, anti-Xa only
Warfarin - inhibits VKORC1 -> dec reduced vitamin K -> dec gamma-carboxylation of II, VII, IX, X, protein C and S
DOACs - direct active-site inhibition, antithrombin-independent
- Dabigatran - direct thrombin (IIa)
- Rivaroxaban, apixaban, edoxaban - direct Xa

	Onset	Monitoring	Reversal
Warfarin	Days	INR	Vitamin K + PCC (or FFP)
UFH	Minutes	APTT or anti-Xa	Protamine (full)
LMWH	Hours	Anti-Xa if renal/obese/pregnant	Protamine (~60%)
Dabigatran	1-2 h	TCT/dilute TT	Idarucizumab
Xa inhibitors	1-4 h	Drug-specific anti-Xa	Andexanet alfa, or PCC
Aspirin	Hours	None	Platelets, desmopressin
Clopidogrel	Days (or 6 h with loading)	None	Platelets

Warfarin's early prothrombotic window - protein C (t-half 8 h) falls before factor II (t-half 60 h) -> skin necrosis in protein C deficiency; overlap with heparin for at least 5 days AND until INR >2 for 24 h
Clopidogrel and CYP2C19 - loss-of-function alleles (2, 3) and omeprazole reduce activation; use pantoprazole
Prasugrel - contraindicated with prior stroke/TIA; avoid over 75 years or under 60 kg
HIT - IgG against PF4-heparin; UFH >> LMWH; 4T score, then anti-PF4 ELISA and a functional assay
- Stop all heparin, do NOT give platelets, do NOT start warfarin alone -> use a direct thrombin inhibitor (argatroban, bivalirudin) or fondaparinux

Antiplatelets for arterial disease; anticoagulants for venous and cardioembolic disease - and the failure to distinguish is a common error
- AF -> anticoagulant, not aspirin
- ACS/stent -> dual antiplatelet therapy
DOACs are preferred over warfarin in non-valvular AF and VTE; warfarin remains mandatory for mechanical valves and moderate-severe mitral stenosis, and for antiphospholipid syndrome with triple positivity
Renal function drives DOAC choice - dabigatran is ~80% renally cleared (avoid CrCl <30); apixaban least renally dependent
Perioperative: stop DOACs 24-48 h before (longer for high bleeding risk or dec eGFR); no bridging needed for most, unlike warfarin
Triple therapy (DAPT + anticoagulant) after PCI in AF - shorten aspirin to the peri-procedural period, then clopidogrel + DOAC

3 more sections, plus exam facts

Premium unlocks every note across every specialty, and the full exam fact library behind it.