Warfarin Initiation

Warfarin is a vitamin K antagonist with a narrow safety margin and a wide variation in dose between patients. It is started on a low, fixed dose with early INR checks, and heparin cover is added when immediate anticoagulation is needed.

Baseline. INR, full blood count, liver tests, creatinine, pregnancy test for women of childbearing age, and a drug and alcohol history. Target INR is 2.0 to 3.0 for most indications, and 2.5 to 3.5 for high-risk mechanical valves.

Dose determinants. Age, weight, liver disease, heart failure, poor nutrition, thyroid disease and interacting drugs reduce the dose. Patients of African ancestry tend to need higher average doses, and genetic variation in CYP2C9 and VKORC1 explains part of the variation.

• Usual start: warfarin 5 mg orally once daily in the evening for the first 2 days. Large loading doses of 10 mg are not advised.
• Lower start (2 to 3 mg daily): age over 70 years, weight under 50 kg, liver disease, heart failure, malnutrition, recent surgery, and interacting drugs (amiodarone, azole antifungals, metronidazole, cotrimoxazole, macrolides).
• Check INR on days 3 to 4 (after 3 doses), then every 2 to 3 days, adjusting the dose until two consecutive results are in range, then weekly, then every 4 weeks (up to 12 weeks in very stable patients).
• Venous thromboembolism and mechanical valves: give enoxaparin 1 mg/kg twice daily (or unfractionated heparin) together with warfarin for at least 5 days and until INR is 2.0 or more for 24 hours (2 consecutive readings for mechanical valves). Atrial fibrillation without recent stroke does not need heparin cover.
• Skin necrosis risk (protein C deficiency): start warfarin only under full heparin cover with a low dose.

Counselling. Keep vitamin K intake steady, limit alcohol, report bleeding, black stools, bruising and falls, check any new medicine with the clinic, and carry an alert card. Take the dose at the same time each evening. If a dose is missed, take it the same day and never double.

Pregnancy. Contraindicated in weeks 6 to 12 and avoided throughout except for mechanical valves under specialist direction.

Interactions. Antibiotics, azoles, amiodarone and paracetamol over 2 g daily for several days raise INR; rifampicin, carbamazepine, phenytoin and St John’s wort lower it. Recheck INR within 3 to 5 days of starting or stopping any of them.

Older adults. Start at 2 to 3 mg daily and increase slowly, because falls and bleeding risk are higher.

Kidney and liver disease. Lower doses and more frequent checks.

Special groups. In East Africa, tuberculosis regimens with rifampicin and antiretroviral drugs destabilise INR, and clinics with limited INR testing benefit from point-of-care INR devices and stable, simple dosing.

Monitoring. INR on days 3 to 4, every 2 to 3 days until stable, then weekly and up to every 4 weeks, with a full blood count and liver tests yearly. Aim for time in therapeutic range over 70%.

Referral and escalation. Escalate for INR over 4.5 with bleeding, INR persistently out of range, unexplained high doses (check adherence and interactions), and suspected skin necrosis.

Stopping. Stop warfarin after planned treatment duration. Tapering is not needed. Before elective procedures, stop 5 days before and follow a peri-procedure plan.