Warfarin blocks vitamin K, heparin activates antithrombin, DOACs block Xa or thrombin
Mnemonic
Group by which factor is hit:
- Warfarin - inhibits vitamin K epoxide reductase, so factors II, VII, IX, X (“1972”) and proteins C and S. Monitored by INR, reversed by vitamin K and prothrombin complex concentrate
- Unfractionated heparin - potentiates antithrombin III, inhibiting thrombin (IIa) and Xa. Monitored by APTT, reversed by protamine
- Low molecular weight heparin - mainly anti-Xa. No routine monitoring, renally cleared
- Direct oral anticoagulants
- Rivaroxaban, apixaban, edoxaban - Xa inhibitors. "-xaban blocks Xa"
- Dabigatran - direct thrombin inhibitor, reversed by idarucizumab
“The xabans block ten, dabigatran blocks two.”
Warfarin is transiently procoagulant on starting, because protein C has a shorter half life than the clotting factors, which is why heparin cover is needed and why skin necrosis occurs in protein C deficiency.
Mechanical heart valves and antiphospholipid syndrome still require warfarin, since the direct oral anticoagulants are inferior in both.
Expansion
| Drug | Mechanism | Monitoring | Reversal |
|---|---|---|---|
| Warfarin | Blocks vitamin K epoxide reductase, so factors II, VII, IX, X and proteins C and S are not carboxylated | INR | Vitamin K, prothrombin complex concentrate |
| Unfractionated heparin | Activates antithrombin, inhibiting thrombin and Xa | APTT | Protamine (complete) |
| Low molecular weight heparin | Mainly anti-Xa | Anti-Xa level if needed | Protamine (partial) |
| Fondaparinux | Pure anti-Xa | Anti-Xa | None specific |
| Rivaroxaban, apixaban | Direct Xa inhibitors | None routine | Andexanet alfa |
| Dabigatran | Direct thrombin inhibitor | None routine | Idarucizumab |
Warfarin has a delayed onset because existing factors must be cleared; factor VII falls first (shortest half-life) so the INR rises before full anticoagulation is achieved. Meanwhile protein C also falls quickly, causing transient hypercoagulability, which is why heparin cover is given and why skin necrosis can occur.
Warfarin has innumerable interactions through CYP2C9 and dietary vitamin K, whereas DOACs have fewer, do not need monitoring, and are now first line for most indications other than mechanical valves and antiphospholipid syndrome.