History

Bleeding is the only expected significant clinical manifestation. Internal bleeding may present as any of a vast array of symptoms or be occult. Other possible signs and symptoms include^[14]:

Skin necrosis
Vasculitis
Calciphylaxis
Diarrhea
Renal acidosis

Obtain an accurate history of the amount of warfarin or superwarfarin ingested, when it was ingested, and over what period it was ingested. Additionally, inquire about the circumstances of the ingestion to determine the patient's disposition. If the ingestion was suicidal or surreptitious in nature, the history may be difficult to obtain or the patient or caregiver may give misleading information.

An accurate medication list is important because many drugs increase or decrease the metabolism of warfarin (see Overview/Etiology).

The toxic dose of warfarin is highly variable. Generally, a single ingestion of warfarin (10-20 mg) does not cause serious intoxication. In contrast, long-term or repeated ingestion of even small amounts of warfarin (2-5 mg/day) eventually can lead to significant anticoagulation, especially in the presence of interacting drugs. Patients with hepatic dysfunction, malnutrition, or a bleeding diathesis are at the greatest risk of toxicity from warfarin use.

Superwarfarins are extremely potent and can produce prolonged effects even after a small ingestion; as little as 1 mg in an adult can cause coagulopathy.

Physical Examination

Do not expect to see physical evidence of bleeding after an acute ingestion for at least 24 hours. Life-threatening complications include massive gastrointestinal bleeding and intracranial hemorrhage. More common findings of excessive anticoagulation are ecchymoses, subconjunctival hemorrhage, epistaxis, vaginal bleeding, bleeding gums, or hematuria.

In all patients, if prolongation of the prothrombin time (PT) is observed after an acute ingestion, it may appear in as early as 8-12 hours; however, peak effects commonly are delayed until at least 1-2 days postingestion.

Skin necrosis is a rare but serious manifestation of toxicity and usually occurs within a few days of starting therapy but has been reported up to three years later. Due to the increased subcutaneous fat, the most common sites of necrosis are breasts, abdomen, buttocks, calves and thighs.^[15]

Differential Diagnoses

Lasoff DR. Warfarin and Superwarfarins. Olson KR, Smollin CG, Anderson IB, et al, eds. Poisoning & Drug Overdose. 8th ed. New York: McGraw-Hill; 2022. Chapter 2-158. [Full Text].
Chen BC, Su MK. Antithrombotics. Nelson LS, Howland MA, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS, eds. Goldfrank's Toxicologic Emergencies. 11th ed. McGraw-Hill Education; 2019. 883-907.
Hirsh J, Dalen J, Anderson DR, Poller L, Bussey H, Ansell J, et al. Oral anticoagulants: mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest. 2001 Jan. 119(1 Suppl):8S-21S. [QxMD MEDLINE Link].
Olmos V, Lopez CM. Brodifacoum poisoning with toxicokinetic data. Clin Toxicol (Phila). 2007. 45(5):487-9. [QxMD MEDLINE Link].
Baillargeon J, Holmes HM, Lin YL, Raji MA, Sharma G, Kuo YF. Concurrent use of warfarin and antibiotics and the risk of bleeding in older adults. Am J Med. 2012 Feb. 125(2):183-9. [QxMD MEDLINE Link].
Lane MA, Zeringue A, McDonald JR. Serious bleeding events due to warfarin and antibiotic co-prescription in a cohort of veterans. Am J Med. 2014 Jul. 127(7):657-663.e2. [QxMD MEDLINE Link]. [Full Text].
Gummin DD, Mowry JB, Beuhler MC, Spyker DA, Rivers LJ, Feldman R, et al. 2021 Annual Report of the National Poison Data System(©) (NPDS) from America's Poison Centers: 39th Annual Report. Clin Toxicol (Phila). 2022 Dec. 60 (12):1381-1643. [QxMD MEDLINE Link]. [Full Text].
Budnitz DS, Shehab N, Lovegrove MC, Geller AI, Lind JN, Pollock DA. US Emergency Department Visits Attributed to Medication Harms, 2017-2019. JAMA. 2021 Oct 5. 326 (13):1299-1309. [QxMD MEDLINE Link]. [Full Text].
Ingels M, Lai C, Tai W, Manning BH, Rangan C, Williams SR, et al. A prospective study of acute, unintentional, pediatric superwarfarin ingestions managed without decontamination. Ann Emerg Med. 2002 Jul. 40(1):73-8. [QxMD MEDLINE Link].
Gitter MJ, Jaeger TM, Petterson TM, et al. Bleeding and thromboembolism during anticoagulant therapy: a population- based study in Rochester, Minnesota. Mayo Clin Proc. 1995 Aug. 70(8):725-33. [QxMD MEDLINE Link].
[Guideline] Caravati EM, Erdman AR, Scharman EJ, Woolf AD, Chyka PA, Cobaugh DJ. Long-acting anticoagulant rodenticide poisoning: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol (Phila). 2007. 45(1):1-22. [QxMD MEDLINE Link].
Shah M, Avgil Tsadok M, Jackevicius CA, Essebag V, Eisenberg MJ, Rahme E, et al. Warfarin use and the risk for stroke and bleeding in patients with atrial fibrillation undergoing dialysis. Circulation. 2014 Mar 18. 129(11):1196-203. [QxMD MEDLINE Link].
Patil AS, Shriya S, Dhimole N, More J. Intramural Jejunal Hematoma Causing Intermittent Bowel Obstruction-A Rare Manifestation of Warfarin Toxicity. Surg J (N Y). 2022 Oct. 8 (4):e290-e292. [QxMD MEDLINE Link]. [Full Text].
Penjore Y, Dorji T, Dorji S, Tamang ST. Profile and outcome of patients with Warfarin Toxicity admitted in a tertiary care hospital in Bhutan: a cross-sectional study investigators and institutions. BMC Res Notes. 2023 May 18. 16 (1):81. [QxMD MEDLINE Link]. [Full Text].
Zahra T, Jamil S, Ferman H, Ravikumar Y, Voloshyna D, Shaik TA, et al. Warfarin-Induced Skin Necrosis in a 14-Year-Old Female: A Case Report. Cureus. 2022 Oct. 14 (10):e30354. [QxMD MEDLINE Link]. [Full Text].
Schulman S, Furie B. How I treat poisoning with vitamin K antagonists. Blood. 2015 Jan 15. 125 (3):438-42. [QxMD MEDLINE Link]. [Full Text].
Miller MA, Levy PD, Hile D. Rapid identification of surreptitious brodifacoum poisoning by analysis of vitamin K-dependent factor activity. Am J Emerg Med. 2006 May. 24(3):383. [QxMD MEDLINE Link].
Spahr JE, Maul JS, Rodgers GM. Superwarfarin poisoning: a report of two cases and review of the literature. Am J Hematol. 2007 Jul. 82(7):656-60. [QxMD MEDLINE Link].
Tsutaoka BT, Miller M, Fung SM, et.al. Superwarfarin and glass ingestion with prolonged coagulopathy requiring high-dose vitamin K1 therapy. Pharmacotherapy. 2003 Sep. 23(9):1186-9. [QxMD MEDLINE Link].
Wang Y, Kotik V, Fahim G, Alagusundaramoorthy S, Eltawansy SA, Mathis S, et al. Treatment of brodifacoum overdose with prothrombin complex concentrate. Am J Health Syst Pharm. 2016 Jan 1. 73 (1):e14-7. [QxMD MEDLINE Link].
Chua JD, Friedenberg WR. Superwarfarin poisoning. Arch Intern Med. 1998 Sep 28. 158(17):1929-32. [QxMD MEDLINE Link].
Schulman S, Parpia S, Stewart C, Rudd-Scott L, Julian JA, Levine M. Warfarin dose assessment every 4 weeks versus every 12 weeks in patients with stable international normalized ratios: a randomized trial. Ann Intern Med. 2011 Nov 15. 155(10):653-9. [QxMD MEDLINE Link].
Berling I, Mostafa A, Grice JE, Roberts MS, Isbister GK. Warfarin Poisoning with Delayed Rebound Toxicity. J Emerg Med. 2017 Feb. 52 (2):194-196. [QxMD MEDLINE Link].
Mullins ME, Brands CL, Daya MR. Unintentional pediatric superwarfarin exposures: do we really need a prothrombin time?. Pediatrics. 2000 Feb. 105(2):402-4. [QxMD MEDLINE Link].
Smolinske SC, Scherger DL, Kearns PS, et al. Superwarfarin poisoning in children: a prospective study. Pediatrics. 1989 Sep. 84(3):490-4. [QxMD MEDLINE Link].
[Guideline] Witt DM, Nieuwlaat R, Clark NP, Ansell J, Holbrook A, Skov J, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: optimal management of anticoagulation therapy. Blood Adv. 2018 Nov 27. 2 (22):3257-3291. [QxMD MEDLINE Link]. [Full Text].
Deveras RA, Kessler CM. Reversal of warfarin-induced excessive anticoagulation with recombinant human factor VIIa. Ann Intern Med. 2002. 137(11):884-888. [QxMD MEDLINE Link].
Ilyas C, Beyer GM, Dutton RP, Scalea TM, Hess JR. Recombinant factor VIIa for warfarin-associated intracranial bleeding. J Clin Anesth. 2008 Jun. 20(4):276-9. [QxMD MEDLINE Link].
Nishijima DK, Dager WE, Schrot RJ, Holmes JF. The efficacy of factor VIIa in emergency department patients with warfarin use and traumatic intracranial hemorrhage. Acad Emerg Med. 2010 Mar. 17(3):244-51. [QxMD MEDLINE Link].
Huttner HB, Schellinger PD, Hartmann M, Köhrmann M, Juettler E, Wikner J, et al. Hematoma growth and outcome in treated neurocritical care patients with intracerebral hemorrhage related to oral anticoagulant therapy: comparison of acute treatment strategies using vitamin K, fresh frozen plasma, and prothrombin complex concentrates. Stroke. 2006 Jun. 37(6):1465-70. [QxMD MEDLINE Link].
Kalina M, Tinkoff G, Gbadebo A, Veneri P, Fulda G. A protocol for the rapid normalization of INR in trauma patients with intracranial hemorrhage on prescribed warfarin therapy. Am Surg. 2008 Sep. 74(9):858-61. [QxMD MEDLINE Link].
Dezee KJ, Shimeall WT, Douglas KM, Shumway NM, O'malley PG. Treatment of excessive anticoagulation with phytonadione (vitamin K): a meta-analysis. Arch Intern Med. 2006 Feb 27. 166(4):391-7. [QxMD MEDLINE Link].
Bershad EM, Suarez JI. Prothrombin complex concentrates for oral anticoagulant therapy-related intracranial hemorrhage: a review of the literature. Neurocrit Care. 2010 Jun. 12(3):403-13. [QxMD MEDLINE Link].

Media Gallery

of 0

Author

Kent R Olson, MD, FACEP Clinical Professor of Medicine and Pharmacy, University of California, San Francisco, School of Medicine; Medical Director, San Francisco Division, California Poison Control System

Kent R Olson, MD, FACEP is a member of the following medical societies: American Academy of Clinical Toxicology, American College of Medical Toxicology

Disclosure: Nothing to disclose.

Coauthor(s)

David N Trickey, MD Staff Physician, Department of Emergency Medicine, Martin Army Community Hospital

David N Trickey, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians

Disclosure: Nothing to disclose.

Michael A Miller, MD Clinical Professor of Emergency Medicine, Medical Toxicologist, Department of Emergency Medicine, Texas A&M Health Sciences Center; CHRISTUS Spohn Emergency Medicine Residency Program

Michael A Miller, MD is a member of the following medical societies: American College of Medical Toxicology

Disclosure: Nothing to disclose.

Lisa M Yungmann Hile, MD Consulting Staff, Medical Director of Emergency Medicine Physician Assistant Fellowship Program, Department of Emergency Medicine, Darnall Army Medical Center

Disclosure: Nothing to disclose.

Derrick Lung, MD, MPH, FACEP, FACMT Physician, Department of Emergency Medicine, San Mateo Medical Center

Derrick Lung, MD, MPH, FACEP, FACMT is a member of the following medical societies: American College of Emergency Physicians, American College of Medical Toxicology

Disclosure: Nothing to disclose.

Chief Editor

David Vearrier, MD, MPH Professor of Emergency Medicine, Department of Emergency Medicine, University of Mississippi Medical Center

David Vearrier, MD, MPH is a member of the following medical societies: American Academy of Clinical Toxicology, American College of Medical Toxicology, American College of Occupational and Environmental Medicine

Disclosure: Nothing to disclose.

Acknowledgements

John G Benitez, MD, MPH Associate Professor, Department of Medicine, Medical Toxicology, Vanderbilt University Medical Center; Managing Director, Tennessee Poison Center

John G Benitez, MD, MPH is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Emergency Medicine, American College of Medical Toxicology, American College of Preventive Medicine, Society for Academic Emergency Medicine, Undersea and Hyperbaric Medical Society, and Wilderness Medical Society

Disclosure: Nothing to disclose.

David A Peak, MD Assistant Residency Director of Harvard Affiliated Emergency Medicine Residency, Attending Physician, Massachusetts General Hospital; Consulting Staff, Department of Hyperbaric Medicine, Massachusetts Eye and Ear Infirmary

David A Peak, MD is a member of the following medical societies: American College of Emergency Physicians, American Medical Association, Society for Academic Emergency Medicine, and Undersea and Hyperbaric Medical Society

Disclosure: Nothing to disclose.

John T VanDeVoort, PharmD Regional Director of Pharmacy, Sacred Heart and St Joseph's Hospitals

John T VanDeVoort, PharmD is a member of the following medical societies: American Society of Health-System Pharmacists

Disclosure: Nothing to disclose.