Warfarin inhibits vitamin K epoxide reductase, depleting active vitamin K and reducing synthesis of the vitamin K-dependent clotting factors II, VII, IX, and X (mnemonic "1972") along with the anticoagulant proteins C and S. Because proteins C and S have shorter half-lives than the clotting factors, an initial prothrombotic state can occur at warfarin initiation. Reversal of warfarin uses vitamin K for slow correction or fresh frozen plasma or 4-factor prothrombin complex concentrate for urgent reversal.
Heparin binds antithrombin III and accelerates its inactivation of thrombin (factor IIa) and factor Xa, with monitoring via aPTT. Low-molecular-weight heparins such as enoxaparin have more predictable pharmacokinetics, longer half-life, subcutaneous administration, and preferential anti-Xa activity; routine monitoring is unnecessary except in renal failure or obesity. Heparin-induced thrombocytopenia (HIT) type II is an immune-mediated reaction in which antibodies against the heparin-PF4 complex paradoxically cause thrombosis along with platelet decline about 5 to 10 days after starting heparin. Management requires stopping all heparin and switching to a non-heparin anticoagulant such as argatroban or bivalirudin; protamine sulfate reverses unfractionated heparin and partially reverses LMWH.
The direct oral anticoagulants include the anti-Xa agents apixaban and rivaroxaban and the direct thrombin inhibitor dabigatran, all of which eliminate the need for INR monitoring. Targeted reversal agents are available: idarucizumab for dabigatran and andexanet alfa for the anti-Xa DOACs, providing rapid reversal in life-threatening bleeding.