Warfarin

Warfarin is a vitamin K antagonist

• Inhibit vitamin K-dependent clotting factors (II, VII, IX, X), and
• Inhibit protein C & S

• Embolism prophylaxis in atrial fibrillation and rheumatic heart disease
• Embolism prophylaxis in patients with prosthetic heart valves
• Embolism treatment or prophylaxis of VTEVenous thromboembolism
• TIATransient ischaemic attack

Patients who take warfarin should be advised of the following:

• Adhere strictly to the prescribed dosing schedule
• Report any signs of bleeding (e.g. unusual bruising, haematuria, melena, headache)
• Dietary vitamin K intake should remain consistent (avoid sudden increase or decrease in intake of food high in vitamin K – e.g. leafy green vegetables)
• Ensure moderate and consistent alcohol intake (excessive / variable consumption can alter warfarin effect)

If the patient missed a warfarin dose:

• Do not double any subsequent doses
• Take the missed dose ASAP on the same day

Warfarin has an initial paradoxical pro-coagulation state, therefore it should be introduced together with heparin (heparin lead-in) and continued until:

• At least 5 days, and
• INR ≥2 for at least 24 hours

BSH Guidelines (endorsed by NICE CKS and BNF) recommend the following:

• INR target is generally 2.5 +/- 0.5 units (note target range is no longer recommended)
• Some exceptions
  • Mechanical mitral valve → 3.0 / 3.5Target INR in mechanical heart valves aren't straight forward. It depends on the thrombogenicity of the valve and patient-related risk factors. Recommended target INR is either 3.0 or 3.5. Exception being target INR 2.5 in low thrombogenicity with no patient risk factors.
  • Recurrent DVT / PE whilst anticoagulated → 3.5

The INRThe ratio between an individual's prothrombin time (PT) and control samples.  is used to assess and monitor the anticoagulant effect of warfarin.

Recommended INR measurement frequency:

More frequent monitoring is recommended if there is:

• ↑ Risk of over-coagulationExamples provided by NICE CKS include: - severe hypertension - liver disease - renal failure
• ↑ Risk of bleedingExamples provided by NICE CKS include: - INR >4 - >65 y/o
• Adherence to treatment may be difficult

Regardless of INR:

• Stop warfarin
• IV vitamin K (5 mg)
• Prothrombin complex concentrate (PCC)

  PCC contains factors 2, 7, 9 and 10 

If PCC is not available, fresh frozen plasma (FFP) can be given instead, but it is less effective than PCC.

Regardless of INR:

• Stop warfarin (restart when INR <5.0)
• IV vitamin K (1-3 mg)

Depends on INR:

• INR >8.0 → stop warfarin (restart when INR <5.0) + oral vitamin K (1-5 mg)
• INR 5.0-8.0 → withhold 1-2 doses of warfarin + ↓ subsequent doses

Warfarin is usually stopped 5 days before elective surgery

• Oral vitamin K should be given the day before surgery if INR is ≥1.5
• If the patient is at high-risk of thromboembolism (e.g. VTE within the last 3 months, AF with previous stroke / TIA, mitral mechanical heart valve), they may also require LMWH bridging (treatment dose) once warfarin is stopped and to be stopped at least 24 hours before surgery (or 48 hours if the surgery carries a high risk of bleeding)

If warfarin cannot be stopped 3 days before the surgery, anticoagulation should be reversed with low-dose vitamin K.

For dental procedures, warfarin does NOT need to be stopped routinely. However, INR should be checked 24 hours beforehand, and the procedure should only go ahead if INR <4.

If possible, delay the surgery for 6-12 hours to give IV vitamin K to reverse the anticoagulant effect of warfarin.

If the surgery cannot be delayed:

• Give IV vitamin K and prothrombin complex concentrate
• Check INR before surgery