Anticoagulation in critically ill- Warfarin

Question 1

type and use

Answer 1

Warfarin Overview
* Type: Vitamin K antagonist (VKA)
* Use: Prevents thromboembolic events (e.g., DVT, PE, atrial fibrillation, mechanical heart valves)

Question 2

Pharmacology

Answer 2

• Mechanism: Inhibits vitamin K-dependent clotting factors II, VII, IX, X and proteins C and S
  
  • Onset of action: Delayed (48–72 hours)
  • Half-life: 36–42 hours
  • Absorption: Oral, absorbed in small bowel
  • Protein binding: Strongly bound; only unbound is active
  • Metabolism: Via hepatic CYP2C9 enzyme system (genetically variable and drug-inducible)

Question 3

clinical considerations

Answer 3

• Transient prothrombotic effect: Due to shorter half-life of proteins C and S
  
  • Not ideal for ICU use: Due to slow onset and long half-life
  • Preferred in renal impairment: Safer than DOACs in severe renal failure
  • Challenging to manage: Requires frequent INR monitoring and dose adjustment

Question 4

Monitoring

Answer 4

• Test used: INR (International Normalized Ratio)
  
  • INR targets:
  • DVT: 2.0–2.5
  • Mechanical heart valves: 2.5–3.5 (depends on valve type/location

Question 5

Risks and interactions

Answer 5

• High bleeding risk: Especially intracerebral hemorrhage due to genetic variability in metabolism and food interactions
  
  • Frequent interactions: With foods and medications (affects INR stability)
  • BRIDGE trial: Showed increased bleeding with LMWH bridging without thromboembolic benefit (CHADS2 score 1–3 patients)

Bridge Trial:
In patients with atrial fibrillation who had warfarin treatment interrupted for an elective operation or other elective invasive procedure, forgoing bridging anticoagulation was noninferior to perioperative bridging with low-molecular-weight heparin for the prevention of arterial thromboembolism and decreased the risk of major bleeding
Pts with mechanical heart valves excluded

Question 6

Reversal

Answer 6

• Traditional reversal: Vitamin K + fresh frozen plasma (FFP)
  *Bleeding patients where immediate reversal is needed- : Beriplex (4-factor prothrombin complex concentrate)
  
  • Faster INR correction
  • Smaller volume than FFP
  • FDA-approved for urgent reversal

Question 7

Factors limiting Warfarin use

Answer 7

-Slow onset of action
-Unpredictable pharmacokinetics and pharmacodynamics
-Interactions with many different foods and drugs
-Narrow therapeutic index
-Need for frequent monitoring
-Risk of spontaneous (especially cerebral) hemorrhage
-Induction of a transient hypercoagulable state (rare)