Factors that may potentiate the effects of wafarin

A 63-year-old female on long-term warfarin for atrial fibrillation attends the anticoagulation clinic. Despite having a stable INR for the past 4 years on the same dose of warfarin her INR is measured at 5.4.
Which one of the following is most likely to be responsible?
A. St John's Wort
B. Smoking
C. Carrot juice
D. Cranberry juice
E. Camomile tea

Answer:
D. Cranberry juice

Discussion: St John's Wort is an inducer of the P450 enzyme system so would cause the INR to decrease, rather than increase.

Warfarin is an oral anticoagulant which inhibits the reduction of vitamin K to its active hydroquinone form, which in turn acts as a cofactor in the carboxylation of clotting factor II, VII, IX and X and protein C.

Indications
 venous thromboembolism: target INR = 2.5, if recurrent 3.5
 atrial fibrillation, target INR = 2.5
 mechanical heart valves, target INR depends on the valve type and location.

Mitral valves generally require a higher INR than aortic valves.

Patients on warfarin are monitored using the INR (international normalised ration), the ratio of the prothrombin time for the patient over the normal prothrombin time.

Warfarin has a long half-life and achieving a stable INR may take several days. There a variety of loading regimes and computer software is now often used to alter the dose.

Factors that may potentiate warfarin
 liver disease
 P450 enzyme inhibitors, e.g.: amiodarone, ciprofloxacin
 cranberry juice
 drugs which displace warfarin from plasma albumin, e.g. NSAIDs
 inhibit platelet function: NSAIDs

Side-effects
 haemorrhage
 teratogenic, although can be used in breast-feeding mothers
 skin necrosis: when warfarin is first started biosynthesis of protein C is reduced. This results in a temporary procoagulant state after initially starting warfarin, normally avoided by concurrent heparin administration. Thrombosis may occur in venules leading to skin necrosis
 purple toes