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Toxicity, Warfarin and Superwarfarins: Treatment & Medication

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

Treatment

Prehospital Care

Initiate usual supportive measures, including intravenous access if any suggestion of remote or active bleeding is evident. After an acute intentional ingestion, administer activated charcoal per local protocols. Infuse crystalloid solution if signs of significant blood loss are present.

Emergency Department Care

Initiate usual advanced supportive measures. Evaluate for current or remote bleeding with a thorough physical examination, including a rectal examination as indicated to check for occult GI bleeding. If significant bleeding has occurred and the patient is unstable, be prepared to treat the patient with transfusions of packed cells and fresh frozen plasma as first-line therapy. Further evaluation varies, depending on the situation.

• Warfarin and superwarfarin ingestions generally are acute or chronic. In either situation, determine whether the ingestion was accidental or intentional and whether the patient requires long-term anticoagulation (eg, mechanical heart valve, chronic atrial fibrillation).
• For acute ingestions, generally no evidence of bleeding is present on the initial clinical examination, unless the ingestion occurred more than 12-24 hours before ED presentation.
  • Obtain a baseline PT/INR and make arrangements for a repeat measurement in 24-48 hours.
  • Administer activated charcoal if it was not already given in the field.
  • Gastric lavage is unnecessary if rapid administration of activated charcoal is feasible. Do not induce emesis.
  • Treat any co-ingestions, evaluate the patient for suicidal intention, and refer appropriately.
  • Avoid drugs that may enhance bleeding or decrease metabolism of the anticoagulant.
  • Do not administer vitamin K prophylactically because (1) it is not needed in most patients, and (2) its presence masks the onset of anticoagulant effects in the few patients who do require prolonged treatment and follow-up care.
  • If the prothrombin time is elevated, treatment with vitamin K is appropriate (see Medication). Because vitamin K does not immediately restore therapeutic levels of clotting factors, treat patients who are experiencing acute hemorrhage with fresh frozen plasma (FFP). Recombinant activated factor VII, while costly, may have an advantage over FFP in that it does not carry a risk of transmission of viral disease, allergic reaction, or volume overload.⁶
• Chronic intoxication resulting from therapeutic use of warfarin can be evaluated with a careful physical examination and a measurement of the PT and INR.
  • If INR is higher than therapeutic levels but less than 6 and the patient is not bleeding, withhold warfarin for 2-3 days and restart when the INR approaches the therapeutic range.
  • If INR is higher than 6 but less than 10 and the patient is not actively bleeding, or the INR is less than 6 but the patient requires more rapid reversal (eg, for elective surgery), administer 5-10 mg of vitamin K-1 orally with the expectation that the INR will begin to fall within 8 hours with a maximal effect in about 24 hours.
  • If the INR is higher than 10 and the patient is not bleeding, a higher daily dose of oral vitamin K-1 may be administered. In the setting of superwarfarin-induced coagulopathies, 50-200 mg is recommended.
  • If very rapid reversal of anticoagulant effect is essential because of serious bleeding, administer fresh frozen plasma (FFP). Successful reversal of severe coagulopathy and life-threatening hemorrhage has also been reported using recombinant activated factor VII^7,8 or activated prothrombin complex concentrate (APCC).⁹ While costly, these newer therapies may have an advantage over FFP in that they do not carry the same risk of transmission of viral disease, allergic reaction, or volume overload.
  • Note: If the patient has a critical need for ongoing anticoagulation (eg, mechanical heart valve), heparin should be given as a temporary measure while fully reversing the effects of warfarin.
• Chronic ingestions of rodenticide superwarfarin may be intentional (eg, Munchhausen syndrome) and can occur in the setting of child abuse (Munchhausen by proxy). These patients should be admitted for psychiatric or protective services evaluation.

Consultations

Since most warfarin and superwarfarin exposures result in minor or no significant effects, the regional poison control center can aid in decreasing the referral of patients to health care facilities as well as decreasing the performance of unnecessary laboratory tests in minor, accidental exposures. The poison centers and clinical toxicologists may be helpful in evaluating a large anticoagulant overdose and can assist with long-term follow-up care after ingestion of a superwarfarin.

• Obtaining a psychiatric referral is appropriate for intentional ingestions. Contact child welfare or protective services if child abuse is suspected.
• The patient's primary care provider or the local coagulation clinic is an appropriate referral if an accidental overdose occurs and the patient is considered to be at low risk for bleeding complications.
• Consulting a neurosurgeon is appropriate for intracranial hemorrhage.
• Consulting a gastroenterologist is appropriate for most GI bleeds.
  

Medication

Packed red cells and fresh frozen plasma may be required for immediate management of life-threatening hemorrhagic complications. Alternative treatments to FFP include prothrombin complex concentrate (APCC)⁹ or recombinant factor VIIa. Data are limited on the use of recombinant factor VIIa for the reversal of warfarin-induced coagulopathy. In a small study, 13 patients who required rapid reversal of warfarin-induced coagulopathy were treated with recombinant factor VIIa with success.⁸ Successful treatment of severe bleeding in 4 patients with superwarfarin toxicity has also been reported.⁷ On the basis of such limited data, the role of recombinant factor VIIa or APCC in the treatment of warfarin and superwarfarin is unclear.

Vitamin K is the only effective antidote for long-term management, but reversal of anticoagulation takes several hours. Administering vitamin K IV has no advantage, and reports have documented acute cardiovascular collapse after administration by this route, presumably caused by an anaphylactoid reaction. IM or SC administration may cause hematoma. In the authors' opinion, oral administration, when possible, is preferred.

GI decontaminants

Empirically used to minimize systemic absorption of the toxin.

Activated charcoal (Liqui-Char)

Emergency treatment in poisoning caused by drugs and chemicals. Network of pores present in activated charcoal adsorbs 100-1000 mg of drug per gram of charcoal. Does not dissolve in water.
Administer to patients who present 1-2 h postingestion or in patients in whom co-ingestants may delay gastric emptying or gut motility; minimal benefit is expected if more than 4 h have passed since the ingestion.

Antidotes

Used in the management of poisoning and overdose, prevention of toxic effects, or metabolic disorders where toxic substances accrue. Mechanisms of action are variable (eg, antagonists, toxin transformation, altered metabolism, chelation, directed antibodies).

Vitamin K (Phytonadione, AquaMEPHYTON)

Can overcome competitive block produced by warfarin and other related anticoagulants. (Note: Vitamin K-3 (menadione) is not effective for this purpose.) Clinical effect is delayed several hours while liver synthesis of clotting factors is initiated and plasma levels of clotting factors II, VII, IX, and X are gradually restored.
Not to be administered prophylactically. Use only if evidence of anticoagulation exists. Required dose varies with clinical situation, including amount of anticoagulant ingested and whether it is a short-acting or long-acting anticoagulant.

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