title: Warfarin Poisoning with Delayed Rebound Toxicity.
abstract: BACKGROUND
  Intentional poisoning with warfarin is not the same as over-anticoagulation, for which guidelines exist. The coagulopathy resulting from a warfarin overdose is reversed with vitamin K1, the dose and timing of which is often guided by experience with the management of over-anticoagulation with warfarin therapy, rather than acute overdose.
  
  
  METHODS
  We report a case of a 50-year-old man who ingested an unknown amount of his warfarin, venlafaxine, and paracetamol. He presented with an international normalized ratio (INR) of 2.5, which steadily increased over 24 h to 7, despite receiving an initial 1 mg of vitamin K1. He was then treated with 5 mg vitamin K1, and once the INR returned to 4.5, 40 h post ingestion, he was discharged home. He was also treated with a full course of acetylcysteine for the paracetamol overdose. The following day his INR rebounded to 8.5 and he suffered a spontaneous epistaxis requiring readmission; he was treated with low titrated doses of vitamin K1. The warfarin concentration was 74.6 μg/mL 26 h post ingestion and decreased to 3.7 μg/mL over 72 h. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Our case highlights the risk of a rebound elevated INR even 3 days after acute warfarin overdose despite treatment with vitamin K1. Understanding the pharmacokinetics of vitamin K1in comparison with warfarin, repeat INR testing, and continued treatment with oral vitamin K1may help avoid complications of rebound coagulopathy in warfarin overdose.
authors.affiliation: Clinical Toxicology Research Group, University of Newcastle, Newcastle, New South Wales, Australia; Department of Clinical Toxicology and Pharmacology, Calvary Mater Newcastle, Newcastle, New South Wales, Australia.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Berling
authors.affiliation: Therapeutics Research Centre, University of Queensland, Brisbane, Australia; Pharmaceutical Chemistry Department, Faculty of Pharmacy, Helwan University, Ain Helwan, Cairo, Egypt.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Mostafa
authors.affiliation: Therapeutics Research Centre, University of Queensland, Brisbane, Australia.
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Grice
authors.affiliation: Therapeutics Research Centre, University of Queensland, Brisbane, Australia; School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Roberts
authors.affiliation: Clinical Toxicology Research Group, University of Newcastle, Newcastle, New South Wales, Australia; Department of Clinical Toxicology and Pharmacology, Calvary Mater Newcastle, Newcastle, New South Wales, Australia.
authors.forename: Geoffrey K
authors.initials: GK
authors.lastname: Isbister
mesh_terms: D000082:Acetaminophen / Q000494:pharmacology / Q000627:therapeutic use; D000111:Acetylcysteine / Q000494:pharmacology / Q000627:therapeutic use; D000437:Alcoholism / Q000150:complications; D000925:Anticoagulants / Q000494:pharmacology / Q000506:poisoning / Q000627:therapeutic use; D003863:Depression / Q000150:complications* / Q000523:psychology; D062787:Drug Overdose / Q000150:complications / Q000188:drug therapy; D004636:Emergency Service, Hospital / Q000458:organization & administration; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D013405:Suicide / Q000523:psychology; D000069470:Venlafaxine Hydrochloride / Q000494:pharmacology / Q000627:therapeutic use; D014812:Vitamin K / Q000494:pharmacology / Q000627:therapeutic use; D014859:Warfarin / Q000506:poisoning* / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D014812:Vitamin K; D000082:Acetaminophen; D014859:Warfarin; D000069470:Venlafaxine Hydrochloride; D000111:Acetylcysteine
keywords: overdose; poisoning; vitamin K1; warfarin