Warfarin and Superwarfarin Toxicity Workup

  • Author: Kent R Olson, MD, FACEP; Chief Editor: Asim Tarabar, MD   more...
 
Updated: Feb 7, 2012
 

Approach Considerations

Blood levels of warfarin are neither readily available nor helpful. Specific levels of superwarfarin rodenticides (eg, brodifacoum) may be useful in cases in which the ingestion is denied or for purposes of estimating the necessary duration of vitamin K1 therapy. However, most reference laboratories do not perform this analysis. (National Medical Laboratory [NMS] in Willow Grove, Pa, offers a qualitative screen for anticoagulant rodenticides and a quantitative analysis for brodifacoum.)

The anticoagulant effect is best quantified by baseline and daily repeated measurement of the PT and the INR, which may not be elevated until 1-2 days postingestion.[9] A normal PT 48-72 hours after ingestion rules out significant ingestion.

Blood levels of vitamin K–dependent clotting factors (II, VII, IX, and X) are decreased if measured, but these are rarely available in a timely fashion and usually do not aid in clinical management. However, depressed levels may provide supporting evidence for suspected poisoning by warfarin or superwarfarins.[10]

Note that a "mixing study" using an aliquot of normal serum mixed with the patient's serum will restore an abnormal PT to normal. This may be useful when trying to distinguish anticoagulation caused by warfarin or a superwarfarin from that caused by a factor inhibitor (eg, lupus anticoagulant) or antifactor antibodies.[11]

Other laboratory tests that may be indicated include a blood count for baseline hemoglobin and/or hematocrit to assess for anemia if the ingestion is more remote. A blood type and crossmatch or antibody screening is indicated if substantial blood loss is suggested.

In addition, other laboratory tests (eg, acetaminophen level) or toxicology screening may be indicated to rule out co-ingestions. If intracranial bleeding is suspected, obtain a noncontrast computed tomography (CT) scan of the head.

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Contributor Information and Disclosures
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 and 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 and American College of Emergency Physicians

Disclosure: Nothing to disclose.

Michael A Miller, MD  Assistant Chief, Department of Emergency Medicine, Tripler Army Medical Center; Medical Toxicologist, Tripler Army Medical Center and Central Texas Poison Center, Scott and White Memorial Hospital

Michael A Miller, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, and 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  Fellow, Medical Toxicology, University of California, San Francisco, School of Medicine; Clinical Instructor, Division of Emergency Medicine, Stanford University Medical Center

Derrick Lung, MD, MPH is a member of the following medical societies: American Academy of Clinical Toxicology, American College of Emergency Physicians, American College of Medical Toxicology, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Chief Editor

Asim Tarabar, MD  Assistant Professor, Director, Medical Toxicology, Department of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital

Disclosure: Nothing to disclose.

Additional Contributors

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.

References

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  2. Su M, Hoffman RS. Anticoagulants. In: Goldfrank's Toxicologic Emergencies. 8th ed. McGraw-Hill; 2006:887-902.

  3. 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. Jan 2001;119(1 Suppl):8S-21S. [Medline].

  4. Olmos V, Lopez CM. Brodifacoum poisoning with toxicokinetic data. Clin Toxicol (Phila). 2007;45(5):487-9. [Medline].

  5. 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. Feb 2012;125(2):183-9. [Medline].

  6. Bronstein AC, Spyker DA, Cantilena LR Jr, Green JL, Rumack BH, Giffin SL. 2009 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 27th Annual Report. Clin Toxicol (Phila). Dec 2010;48(10):979-1178. [Medline].

  7. 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. Jul 2002;40(1):73-8. [Medline].

  8. Gitter MJ, Jaeger TM, Petterson TM, et al. Bleeding and thromboembolism during anticoagulant therapy: a population- based study in Rochester, Minnesota. Mayo Clin Proc. Aug 1995;70(8):725-33. [Medline].

  9. [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. [Medline].

  10. Miller MA, Levy PD, Hile D. Rapid identification of surreptitious brodifacoum poisoning by analysis of vitamin K-dependent factor activity. Am J Emerg Med. May 2006;24(3):383. [Medline].

  11. Spahr JE, Maul JS, Rodgers GM. Superwarfarin poisoning: a report of two cases and review of the literature. Am J Hematol. Jul 2007;82(7):656-60. [Medline].

  12. Tsutaoka BT, Miller M, Fung SM, et.al. Superwarfarin and glass ingestion with prolonged coagulopathy requiring high-dose vitamin K1 therapy. Pharmacotherapy. Sep 2003;23(9):1186-9. [Medline].

  13. Chua JD, Friedenberg WR. Superwarfarin poisoning. Arch Intern Med. Sep 28 1998;158(17):1929-32. [Medline].

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  15. Mullins ME, Brands CL, Daya MR. Unintentional pediatric superwarfarin exposures: do we really need a prothrombin time?. Pediatrics. Feb 2000;105(2):402-4. [Medline].

  16. Smolinske SC, Scherger DL, Kearns PS, et al. Superwarfarin poisoning in children: a prospective study. Pediatrics. Sep 1989;84(3):490-4. [Medline].

  17. Bershad EM, Suarez JI. Prothrombin complex concentrates for oral anticoagulant therapy-related intracranial hemorrhage: a review of the literature. Neurocrit Care. Jun 2010;12(3):403-13. [Medline].

  18. Deveras RA, Kessler CM. Reversal of warfarin-induced excessive anticoagulation with recombinant human factor VIIa. Ann Intern Med. 2002;137(11):884-888. [Medline].

  19. Ilyas C, Beyer GM, Dutton RP, Scalea TM, Hess JR. Recombinant factor VIIa for warfarin-associated intracranial bleeding. J Clin Anesth. Jun 2008;20(4):276-9. [Medline].

  20. 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. Mar 2010;17(3):244-51. [Medline].

  21. 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. Jun 2006;37(6):1465-70. [Medline].

  22. 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. Sep 2008;74(9):858-61. [Medline].

  23. 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. Feb 27 2006;166(4):391-7. [Medline].

 
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