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Warfarin: In Preparation


Learning objectives

Introduction

Warfarin is an acronym for Wisconsin Alumni Research Foundation with the "arin" ending for coumarins. It is an anticoagulant as it mainly inhibits the vitamin K-dependent synthesis of biologically active forms of the calcium-dependent clotting factors II, VII, IX and X, as well as the regulatory factors protein C, protein S, and protein Z.

One of the major drawbacks is that it crosses the placental barrier during pregnancy which can result in fetal bleeding, spontaneous abortion, preterm birth, stillbirth, and neonatal death. Additional adverse effects such as necrosis, purple toe syndrome, osteoporosis, valve and artery calcification, and drug interactions have also been documented with warfarin use.

Indications

  • Anticoagulation with warfarin significantly reduces the morbidity and mortality related to arterial and venous thromboembolism

Exclusion Criteria

  • Exclusion criteria used in the major intervention trials of anticoagulation for patients with atrial fibrillation 13,19
  • Bleeding disorder or abnormal coagulation at baseline
  • Recent stroke or transient ischaemic attack (previous two years)
  • Uncontrolled hypertension (> 180/100 mmHg)
  • Active bleeding
  • Haemorrhagic retinopathy
  • History of intracranial haemorrhage
  • Use of non-steroidal anti-inflammatory drugs
  • Chronic alcohol abuse
  • Risk of gastrointestinal bleeding (active peptic ulcer disease, positive faecal occult blood testing, known oesophageal varices)
  • Planned surgery or invasive procedure
  • Pregnancy or breastfeeding
  • Psychiatric disorder or dementia
  • Expected poor compliance
  • Limited life expectancy
  • Significant renal dysfunction (creatinine > 0.25 mmol/L)
  • Platelet count < 100 x 109/L

Side effects

  • The risk of major bleeding in the atrial fibrillation intervention trials was 1-4% per year, with an intracranial bleeding rate of 0.2-0.5% per year. The fatality rate mirrored the intracranial bleeding rate.5In observational studies of ambulatory patients the risk of major bleeding is 4-9% per annum.6,7
  • Major determinants of warfarin-induced bleeding include the intensity of anticoagulation, patient characteristics, the concomitant use of drugs that interfere with haemostasis, and the length of therapy.Before prescribing warfarin the risk of bleeding should be evaluated and discussed with each patient.
  • The risk of bleeding increases dramatically when the International Normalised Ratio (INR) exceeds 4.0.9,10An INR greater than 4.0 is probably the most important risk factor for intracranial haemorrhage, independent of the indication for warfarin.5
  • The risk of major bleeding is greatest in the first month of therapy (3%) and decreases with time to 0.8% per month for the remainder of the first year and to 0.3% per month thereafter.7

Management

  • T

References

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