Warfarin

Contraindications to Warfarin

• Bleeding diathesis
• Previous GI bleeding
• Intracranial hemorrhage/aneurysm/retinopathy
• Severe hypertension
• Bacterial endocarditis
• Alcoholism
• Unsupervised dementia
• Frequent falls
• First trimester of pregnancy

Other Risk Factors for Adverse Events on Warfarin

• Elderly
• Polypharmacy
• Renal impairment
• Hepatic impairment
• Pregnancy
• Recent surgery/trauma/heart failure/thyrotoxicosis

Advice on Warfarin

Nature of Warfarin

• Warfarin is an oral anticoagulant that thins the blood to prevent clot formation in the legs and other parts of the body.

Benefits

• Recommended for the prevention of recurrent DVT due to the risk of potentially life-threatening pulmonary embolism (PE).

Risks

1. Bleeding
   • Major bleeding < 2% per year.
   • INR is a major determinant, especially if > 3.
   • Bleeding is most likely in the first 3 months of therapy.
2. Risk in Pregnancy (Teratogenicity)
   • Recognized teratogen (Category D) – crosses placenta.
   • Contraindicated in pregnancy.
   • First trimester: Fetal warfarin syndrome (FWS)/warfarin embryopathy (bone stippling & nasal hypoplasia).
   • Third trimester: Perinatal fetal or placental hemorrhage.
3. Infrequent Idiosyncratic Reactions (Type B)
   • Rashes
   • Purple discoloration of toes
   • Skin necrosis
   • Fever
   • Cholesterol embolism
   • Allergic reactions
   • Alopecia
   • Nausea & vomiting
   • Hepatic dysfunction
   • Diarrhea

Interactions

• Warfarin is metabolized by liver enzymes (cytochrome P450). Many medications and herbal preparations can affect its absorption, binding, and metabolism.

1. Drugs that Inhibit Cytochrome P450 Enzymes (Increased Effect)
   • Antibiotics: erythromycin, ciprofloxacin, co-trimoxazole, metronidazole, fluconazole.
2. Drugs that Induce Hepatic Enzymes (Reduced Effect)
   • Antibiotics: rifampicin.
   • Antiepileptics: carbamazepine, phenytoin.
   • St. John’s Wort
   • Alcohol
3. Antiplatelet Drugs (Additive Effect – Avoid)
   • Aspirin
   • Clopidogrel
   • Dipyridamole

Monitoring

1. Controlled Initiation with Heparin
   • Use heparin to prevent procoagulation-mediated thrombosis.
   • Daily monitoring until a stable therapeutic dose is established.
2. Regular Monitoring of INR
   • Regular blood tests (weekly for the first month; monthly thereafter).
   • Aim for INR 2-3; mechanical heart valves require INR 2.5-3.5.
   • Patients to call for results within 24 hours and adjust dose if necessary.
3. Patient Education (Anticoagulant Book)
   • Dosing
     • Same brand of tablets.
     • Same time every day.
     • Emphasize adherence.
   • Lifestyle
     • Dietary Consistency:
       • Maintain a consistent intake of vitamin K, which is found in green leafy vegetables (e.g., spinach, broccoli, kale).
       • Avoid sudden changes in the amount of vitamin K in your diet, as this can affect your INR.
     • Alcohol:
       • Limit alcohol intake to no more than 1-2 standard drinks per day, as excessive alcohol can increase bleeding risk.
     • Exercise:
       • Engage in regular physical activity
       • avoid contact sports or activities that increase the risk of injury
     • Side Effects
       • Heightened awareness of signs of bleeding: headache, abdominal pain, melena, hematuria, nosebleeds.
     • Pregnancy
       • Use barrier contraception.
       • Inform doctor if pregnant.
     • Interactions
       • Avoid aspirin.
       • Inform pharmacist and doctor about any new medications (prescription, herbal, vitamin supplements).
       • INR tested after 4 days of new drug and at the end of the course.
     • Inform Healthcare Providers
       • Inform physiotherapist, podiatrist, chiropractor, dentist.
     • Surgery
       • Stop warfarin 4-5 days prior. Substitute with unfractionated or low-molecular-weight heparin subcutaneously.
     • Medical Alert:
       • Consider wearing a medical alert bracelet indicating you are on warfarin.
     • Travel:
       • If traveling, ensure you have enough medication and arrange for INR testing if you will be away for an extended period.

Complications to Watch Out For

• Signs of Bleeding:
  • Unusual bruising or bleeding (e.g., gums, nosebleeds, heavier menstrual periods).
  • Dark, tarry stools or blood in your urine.
  • Severe headaches, dizziness, or weakness (potential signs of internal bleeding).
  • Prolonged bleeding from cuts or injuries.
• Signs of Blood Clots:
  • Swelling, pain, or tenderness in your legs (potential DVT).
  • Sudden shortness of breath, chest pain, or coughing up blood (potential PE).

Warfarin Reversal

No Bleeding

• INR 5 to 9
  • Cease warfarin therapy; consider reasons for elevated INR and patient-specific factors.
  • Vitamin K:
    • Phytomenadione 1 to 2 mg orally OR
    • Phytomenadione 0.5 to 1 mg IV
• INR 9 or Higher
  • Low risk of bleeding: cease warfarin therapy and give vitamin K:
    • Phytomenadione 2.5 to 5 mg orally OR
    • Phytomenadione 1 mg IV
  • High risk of bleeding: cease warfarin therapy and give vitamin K:
    • Prothrombinex -VF 25 to 50 units/kg IV PLUS
    • Fresh frozen plasma 150 to 300 mL.

Bleeding

• Clinically significant bleeding with warfarin-induced coagulopathy:
  • Phytomenadione 5 to 10 mg IV PLUS
  • Prothrombinex -VF 25 to 50 units/kg IV PLUS
  • Fresh frozen plasma 150 to 300 mL (if available).