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Toxicity, Warfarin and Superwarfarins: Differential Diagnoses & Workup

Author: Kent R Olson, MD, FACEP, Clinical Professor of Medicine and Pharmacy, University of California San Francisco; Medical Director, San Francisco Division, California Poison Control System
Coauthor(s): David N Trickey, MD, Staff Physician, Department of Emergency Medicine, Carl R Darnall Army Medical Center; Michael A Miller, MD, Assistant Chief, Department of Emergency Medicine, Tripler Army Medical Center Hawaii; Medical Toxicologist, Tripler Army Medical Center and Central Texas Poison Center, Scott and White Memorial Hospital; Lisa M Yungmann Hile, MD, Consulting Staff, Medical Director of Emergency Medicine Physician Assistant Fellowship Program, Department of Emergency Medicine, Darnall Army Medical Center
Contributor Information and Disclosures

Updated: Sep 22, 2009

Differential Diagnoses

Abortion, Threatened
Pediatrics, Gastrointestinal Bleeding
Abruptio Placentae
Plant Poisoning, Glycosides - Coumarin
Anemia, Acute
Pregnancy, Ectopic
Compartment Syndrome, Extremity
Pregnancy, Postpartum Hemorrhage
Disseminated Intravascular Coagulation
Shock, Hemorrhagic
Dysfunctional Uterine Bleeding
Shock, Hypovolemic
Epidural Hematoma
Stroke, Hemorrhagic
Epistaxis
Subarachnoid Hemorrhage
Gastritis and Peptic Ulcer Disease
Subdural Hematoma
Hemophilia, Type A
Thrombocytopenic Purpura
Hemophilia, Type B
Toxicity, Rodenticide
Idiopathic Thrombocytopenic Purpura
Vitreous Hemorrhage
Munchausen Syndrome
Munchausen Syndrome by Proxy
Pediatrics, Child Abuse

Other Problems to Be Considered

Liver failure
Factor X deficiency
Factor V deficiency
Afibrinogenemia
Dysfibrinogenemia
Vitamin K deficiency
Malabsorptive states
Domestic violence
Retroperitoneal hemorrhage

Workup

Laboratory Studies

  • Blood levels of warfarin are neither readily available nor helpful. Specific levels of superwarfarin rodenticides (eg, brodifacoum) may be useful in cases where 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, Pennsylvania, 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 prothrombin time (PT) and the international normalized ratio (INR), which may not be elevated until 1-2 days postingestion.
    • 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.4
    • Note: A "mixing study" using an aliquot of normal serum mixed with the patient's serum will restore an abnormal prothrombin time 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 anti-factor antibodies.5
  • Other laboratory tests that may be indicated include a blood count for baseline hemoglobin and/or hematocrit or 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.

Imaging Studies

  • If intracranial bleeding is suggested, obtain a noncontrast CT scan of the head.

More on Toxicity, Warfarin and Superwarfarins

Overview: Toxicity, Warfarin and Superwarfarins
Differential Diagnoses & Workup: Toxicity, Warfarin and Superwarfarins
Treatment & Medication: Toxicity, Warfarin and Superwarfarins
Follow-up: Toxicity, Warfarin and Superwarfarins
References
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References

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

  2. Bronstein AC, Spyker DA, Cantilena LR Jr, Green JL, Rumack BH, Heard SE. 2007 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 25th Annual Report. Clin Toxicol (Phila). Dec 2008;46(10):927-1057. [Medline]. [Full Text].

  3. 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].

  4. [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].

  5. 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].

  6. 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].

  7. Zupancic-Salek S, Kovacevic-Metelko J, Radman I. Successful reversal of anticoagulant effect of superwarfarin poisoning with recombinant activated factor VII. Blood Coagul Fibrinolysis. Jun 2005;16(4):239-44. [Medline].

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

  9. Junagade P, Grace R, Gover P. Fixed dose prothrombin complex concentrate for the reversal of oral anticoagulation therapy. Hematology. Oct 2007;12(5):439-40. [Medline].

  10. Anderson IB. Coumarin and related rodenticides. In: Poisoning and Drug Overdose. 2nd ed. Appleton & Lange; 1994:143-145.

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

  12. 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].

  13. Hirsh J, Dalen JE, Deykin D, et al. Oral anticoagulants. Mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest. Oct 1995;108(4 Suppl):231S-246S. [Medline].

  14. Hoffman RS, Kierenia T. Anticoagulants. In: Goldfrank's Toxicologic Emergencies. 5th ed. Appleton & Lange; 1994:609- 626.

  15. Integrated Medical Curriculum. Clinical Pharmacology Online. 2000.

  16. 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].

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

  18. 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].

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Further Reading

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Keywords

superwarfarin toxicity, warfarin, Coumadin, brodifacoum, diphenadione, chlorophacinone, bromadiolone, coumarin, vitamin K, vitamin K-1, bis -hydroxycoumarin, superwarfarin anticoagulants, S isomer metabolism, warfarin effect, superwarfarin rodenticides, brodifacoum, ingestion of superwarfarin

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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; 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, Carl R Darnall Army Medical Center
David N Trickey, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, and Emergency Medicine Residents Association
Disclosure: Nothing to disclose.

Michael A Miller, MD, Assistant Chief, Department of Emergency Medicine, Tripler Army Medical Center Hawaii; 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: None None None

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.

Medical Editor

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.

Pharmacy Editor

John T VanDeVoort, PharmD, Regional Director of Pharmacy, Sacred Heart & 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.

Managing Editor

John G Benitez, MD, MPH, FACMT, FACPM, FAAEM, Associate Professor, Department of Medicine, Clinical Pharmacology Division, Vanderbilt University; Managing Director, Tennessee Poison Center
John G Benitez, MD, MPH, FACMT, FACPM, FAAEM is a member of the following medical societies: 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.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, 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.

 
 
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