Anticoagulants

Vitamin K antagonist (VKA):

• Warfarin

• Mechanism:

  • Inhibit hepatic synthesis of vitamin K–dependent clotting factors (II, VII, IX, X)

  • Decreases proteins C and S

• Eliminated by hepatic metabolism

• Requires close INR monitoring

  • INR interpretation may be challenging in significant hepatic dysfunction because liver disease can elevate the baseline INR

• Consider if other agents are contraindicated

Direct oral anticoagulants (DOAC):

• Classes:

  • Direct thrombin (IIa) inhibitors

    • Dabigatran

  • Direct factor Xa inhibitors

    • Apixaban, Rivaroxaban, Edoxaban

• Mixed hepatic/renal clearance

  • Renal clearance:

    • Dabigatran (80%) > Edoxaban (50%) > Rivaroxaban (35%) > Apixaban (27%)

• Require dose adjustment or avoidance in significant renal dysfunction (CrCl <30 mL/min)

• Avoided in moderate-to-severe hepatic dysfunction (Child-Pugh B/C or significant LFT elevation)

• Associated with a higher risk of GI bleeding in patients with GI malignancy

Indirect inhibitors:

• Classes:

  • Unfractionated Heparin (UFH)

    • Potentiates antithrombin → Inhibits both thrombin and factor Xa

    • Primarily reticuloendothelial/hepatic clearance (10% renal)

    • Preferred in:

      • Severe renal dysfunction

      • Rapid reversal is needed

  • Low-Molecular-Weight Heparins (LMWH)

    • Dalteparin, Enoxaparin

    • Potentiates antithrombin → Predominantly inhibits factor Xa (less inhibition of thrombin)

    • Preferred in:

      • GI malignancy

      • If DOACs are contraindicated

    • Mostly renal clearance

    • Requires dose adjustment and possible anti-Xa monitoring in renal dysfunction

  • Synthetic pentasaccharide

    • Fondaparinux

    • Potentiating antithrombin → Inhibit factor Xa

    • Almost entirely renal clearance

IN PROGRESS...