Warfarin

Question 1

Warfarin MOA

Answer 1

-vitamin K is a cofactor for the enzymatic activation of clotting factors via gamma carboxylation at glutamic acid residue

(“Vitamin K medic stopping the bleeding”)
(“Vit K medic applies gamma shaped bandage”)

-Warfarin blocks vitamin K epoxide reductase, this is required for activation of Vitamin K thus preventing clotting factors 2,7,9,10, and protein C and S from being produced

(“Warhead destroying V-KOR supply ship from which the vit K medic is getting the gamma bandages”)

• Proteins C and S are anticoagulants
  (“Corporal and sergeant hold their troops back”)

Question 2

Warfarin Properties

Answer 2

-Onset of action is not immediate, not for acute thrombotic events

• onset of action is 8-12 hours, full clinical effect takes 3 days
  (“Delayed warhead detonation”)

-factor VII (7) is the first clotting factor to be reduced when starting warfarin
(“soldier VII is wounded”)

• oral administration
  (“Soldier with open mouth leaning on warfarin bomb”)

-Long half life (6 hours)
(“Long tapering flag”)

Question 3

which lab value should be monitored when Warfarin therapy is indicated ?

Answer 3

-PT time (Prothrombin time)

• a measure of the function of the extrinsic coagulation pathway - factor VII is the main component

(“Para trooping soldier VII landing extrinsically”)

-INR [international normalized ration] is also used to measure warfarin activity

• Goal INR 2-3 for prevention and treatment of thrombosis
  (“INtercom Radio worn by paratrooper calibrated to 2-3”)

Question 4

Warfarin is used to treat …

Answer 4

• long term anticoagulation in atrial fibrillation
• 3-6 months

-used as DVT prophylaxis
(“warship protecting the ileofemoral river”)

• acute treatment for DVT is IV Heparin because Warfarin has delayed onset

(“tv showing Irregularly irregular heart signal”)

Question 5

Warfarin Side effects

Answer 5

• INCREASED RISK OF BLEEDING !
• may precipitate to intracerebral hemorrhage

-can cross the placental barrier and can cause a hemorrhagic disorder or prevent carboxylation reactions in bone.
(“Tarantula symbol on warfarin warhead”)

-vit K deficiency

-the anticoagulation protein C is reduced early in warfarin therapy, resulting in a hypercoagulable state initially
(“Soldiers charging past the injured corporal”)

• warfarin induced skin necrosis due to early hypercoagulable state (“Black soot on corporal”)
• coadministration of heparin when starting warfarin therapy prevents the early hypercoagulable state-heparin bridge
  (“Heparin hunters patrolling the bridge”)

→ skin necrosis risk is increased with a hereditary protein C deficiency

​- warfarin is a substrate of cytochrome P-450
(“CYP-450 chrome tank crushing warhead”)

• increase P450→decrease effects
  rifampin
  phenobarbital
  phenytoin
• decrease P450→ increase effects
  antibiotics
  antifungals
  SSRI’s

Question 6

how can warfarin antiacoagulation be reversed?

Answer 6

-delayed effect-warfarin anticoagulation can be reversed with vitamin K
(“distant Vit K medic reinforcements”)

-immediate reversal-fresh frozen plasma (FFP) provides coagulation factors for immediate warfarin anticoagulation reversal
(“FFP fighter pilot”)