Anticoagulants

Vivian Imbriotis | July 5, 2026

Warfarin, unfractionated heparin, and low molecular weight heparins are of most exam relevance. Bivalrudin has been asked about once.

Pharmaceutics

  • Glycosaminoglycan
  • Available IV and subcut

PK

  • A: 0% oral
  • D: highly protein-bound. Confined to plasma volume Vd \(\approx\)0.1L/kg
  • M: Sequested into reticuloendothelial cells \(\to\) degraded into inactive metabolites
  • E: Saturatable kinetics. Half-time increases with increasing dose (30 minutes \(\to\) 2 hours)

PD

  • Mechanism: binds to ATIII, increasing affinity for XIa, IXa, Xa and thrombin \(\to\) inhibition of intrinsic + common pathway of coagulation cascade \(\to\) anticoagulation
  • AEs: bleeding, HIT, osteopenia, aldosterone deficiency \(\to\) RTA4, LFT derangement
  • Heparin induced thrombocytopenia: platelet factor 4 is a component of platelet granules.Heparin binds to PF4 \(\to\) Abs formed against heparin-PF4 complex \(\to\) antigen-antibody complexes form. These bind to and activate platelets \(\to\) more PF4 release \(\to\) positive feedback loop. Platelet activation initiates coagulation \(\to\) platelet consumption.
  • Monitoring: APTT, ACT
  • Reversal: Protamine

Pharmaceutics

  • Glycosaminoglycan
  • Available IV and subcut

PK

  • A: 0% oral
  • D: Less protein-bound than unfractionated heparin. Confined to plasma volume Vd \(\approx\)0.1L/kg
  • M: Metabolized by liver \(\to\) partially active metabolites.
  • E: 40% of metabolites excreted in urine. Half-life 6 hours.

PD

  • Mechanism: binds to ATIII, increasing affinity for Xa (but not thrombin) \(\to\) inhibition of common pathway of coagulation cascade \(\to\) anticoagulation
  • AEs: bleeding, HIT (rare)
  • Monitoring: Anti-Xa
  • Reversal: Partially reversed by protamine

Pharmaceutics

  • Coumarin derivative
  • Oral tablets

PK

  • A: 100% oral
  • D: 99% protein bound; insoluble in water. Confined to plasma volume Vd \(\approx\)0.1L/kg
  • M: Metabolized by liver CYP2C9 \(\to\) inactive metabolites.
  • E: Metabolites excreted in urine. Half-life ~3 days.

PD

  • Mechanism: Competative inhibitor of vitamin K reductase. Synthesis of factors II VII IX X requires reduced vitamin K. Warfarin prevents the oxydised form being reduced for re-use; therefore reduces synthesis of factors II VII IX X. Low factor levels \(\to\) anticoagulation
  • AEs: bleeding, skin necrosis, calciphylaxis
  • Monitoring: INR (and therefore PT)
  • Slow reversal: vitamin K (provides lots of reduced vitamin K as substrate for hepatic synthesis; takes ~12 hours to peak effect
  • Immediate reversal: Beriplex; contains factors II VII IX X.

Direct thrombin inhibitor. IV only. Half-life 20 minutes. Monitored by APTT. Only adverse effect is bleeding.

These are all direct, reversible enzyme inhibitors...

  • Of thrombin (dabigatran)
  • Of Xa (Apixaban, Rivaroxaban)
  • Dabiagran in renally cleared, largely unchanged.
  • Rivaroxaban and Apixaban are metabolized by CYP3A4 \(\to\) inactive metabolites. ~30% excreted unchanged in urine.
  • All three drugs have half-lives of around 12 hours
  • Reversal: Praxbind for dabigatran, others not directly reversible (Beriplex can be used; we used to have a reversal agent but it has been discontinued in Australia)