Warfarin
This post is under review 25/07/24
CLASS
- anticoagulant
INDICATIONS
- Venous or arterial thromboembolism prophylaxis or treatment
- Thrombophilia: e.g. Factor V Leiden, Anti-phospholipid Syndrome
- Atrial Fibrillation
- Valve replacements
MECHANISM OF ACTION
- Inhibits
- prevents the synthesis of vitamin K dependent clotting factors
- II, VII, IX & X in liver
- prevents the reduction of vitamin K 2, 3-epoxide -> vitamin K
PHARMACEUTICS
- tablets: 0.5, 1, 3 & 5mg
- racemic mixture of warfarin sodium
- **Important note** Marevan and Coumadin ARE NOT interchangeable
DOSE
- 0.2mg/kg to load with in paediatrics
- load with 5, 5, 5mg
- maximum effect at 24-72hrs
INR Targets
- DVT and PE: 2.0-3.0
- Atrial fibrillation: 2.0-3.0
- Bioprosthetic heart valves: 2.0-3.0
- Mechanical heart valves: 2.5-3.5
ADVERSE EFFECTS
- procoagulant effect with initiation of treatment (due to protein C and S depletion)
- bleeding
- teratogenic in pregnancy
- Hypersensitivity
INTERACTIONS
Increase INR: Liver enzyme inhibition, Highly protein bound drugs (e.g. NSAIDs)
Decrease INR: Liver enzyme induction
PHARMACOKINETICS
- Absorption – 100% bioavailable, Onset: 8-12 hours after loading dose
Peak effect up to 72 hours (reflecting T1/2B of previously formed clotting factors - Distribution – 99% protein bound, Vd = 0.15L/kg
- Metabolism – hepatic
- Elimination – Predominantly urine, some faecal, t½B = 40 hrs
REVERSAL
- Conservative: Waiting for new factors to be formed
- Vitamin K administration
- Fresh Frozen Plasma (FFP)
- Prothrombinex
PATIENT EDUCATION
Patients on warfarin therapy should have the following explained:
- Reason for treatment
- Mechanism of action of warfarin
- Time of day to take warfarin (same time of day)
- The INR, target range and need for regular testing
- Signs and symptoms of bleeding
- Effect of illness, injury or any changes in physical status
- Potential effect of invasive procedure, surgery or dental work
- The effects of common over-the-counter (OTC) medication interactions
- The need for consistent intake of vitamin K-rich foods
- Effects of alcohol intake
- Appropriate action if diarrhoea or vomiting occurs
References and Links
CCC Transfusion Series
Blood Products: Cryoprecipitate, Fresh Frozen Plasma (FFP), Platelets, Red Cells (RBCs)
>>> Factor Concentrates: Prothrombinex, Factor VIIa, Fibrinogen Concentrate
Reversal Agents:
>>> Rivaroxaban / Apixaban / Enoxaparin: Andexanet Alfa, Rivaroxaban and Bleeding
>>> Dabigatran: Idarucuzimab, Dabigatran and bleeding
>>> Heparin: Protamine
>>> Warfarin: Vitamin K, FFP, PTx, Warfarin Refersal, Warfarin Toxicity
Testing: Coagulation Studies, TEG / ROTEM (Thromboelastography), Platelet function assays
Conditions: Acute Coagulopathy of Trauma, Disseminated Intravascular Coagulation (DIC), Massive Blood Loss
General Topics: Blood Bank, Blood Conservation Strategies, Blood Product Compatibilities, Blood Transfusion Risks, Massive Transfusion Protocol (MTP), Modifications to Blood Components, Procedures and Coagulopathy, Storage Lesions, TRALI, Transfusion Literature, Transfusion Reactions
CCC Pharmacology Series
Respiratory: Bosentan, Delivery of B2 Agonists in Intubated Patients, Nitric Oxide, Oxygen, Prostacyclin, Sildenafil
Cardiovascular: Adenosine, Adrenaline (Epinephrine), Amiodarone, Classification of Vasoactive drugs, Clevidipine, Digoxin, Dobutamine, Dopamine, Levosimendan, Levosimendan vs Dobutamine, Milrinone, Noradrenaline, Phenylephrine, Sodium Nitroprusside (SNiP), Sotalol, Vasopressin
Neurological: Dexmedetomidine, Ketamine, Levetiracetam, Lignocaine, Lithium, Midazolam, Physostigmine, Propofol, Sodium Valproate, Sugammadex, Thiopentone
Endocrine: Desmopressin, Glucagon Therapy, Medications and Thyroid Function
Gastrointestinal: Octreotide, Omeprazole, Ranitidine, Sucralfate, Terlipressin
Genitourinary: Furosemide, Mannitol, Spironolactone
Haematological: Activated Protein C, Alteplase, Aprotinin, Aspirin, Clopidogrel, Dipyridamole, DOACs, Factor VIIa, Heparin, LMW Heparin, Protamine, Prothrombinex, Tenecteplase, Tirofiban, Tranexamic Acid (TXA), Warfarin
Antimicrobial: Antimicrobial Dosing and Kill Characteristics, Benzylpenicillin, Ceftriaxone, Ciprofloxacin, Co-trimoxazole / Bactrim, Fluconazole, Gentamicin, Imipenem, Linezolid, Meropenem, Piperacillin-Tazobactam, Rifampicin, Vancomycin
Analgesic: Alfentanil, Celecoxib, COX II Inhibitors, Ketamine, Lignocaine, Morphine, NSAIDs, Opioids, Paracetamol (Acetaminophen), Paracetamol in Critical Illness, Tramadol
Miscellaneous: Activated Charcoal, Adverse Drug Reactions, Alkali Therapies, Drug Absorption in Critical Illness, Drug Infusion Doses, Epidural Complications, Epidural vs Opioids in Rib Fractures, Magnesium, Methylene Blue, Pharmacology and Critical Illness, PK and Obesity, PK and ECMO, Sodium Bicarbonate Use, Statins in Critical Illness, Therapeutic Drug Monitoring, Weights in Pharmacology
Toxicology: Digibind, Flumazenil, Glucagon Therapy, Intralipid, N-Acetylcysteine, Naloxone, Propofol Infusion Syndrome
Critical Care
Compendium
FCICM MMed(CritCare) BMed BMedSci
Staff Specialist in Intensive Care at Concord Repatriation General Hospital, and Postgraduate Fellow in Trauma at Royal North Shore Hospital
Grew up on a broadacre farm and found himself in a metropolitan ICU decades later. Always trying to make medical education more interesting and appropriately targeted; pre-hospital and retrieval curious; passionate about equitable access to healthcare; always looking forward to sitting on a tractor at harvest time. Student of LITFL.