Warfarin and Superwarfarin Toxicity Treatment & Management
- Author: Kent R Olson, MD, FACEP; Chief Editor: Asim Tarabar, MD more...
Significant superwarfarin poisoning may require many weeks of vitamin K1 therapy. All patients with signs of active bleeding or at significant risk of life-threatening hemorrhage require admission to the hospital. Suicidal ingestions require psychiatric evaluation, as well as 48-72 hours of observation to monitor for anticoagulation.
With regard to prehospital emergency care, initiate usual supportive measures, including intravenous (IV) 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 red blood cells (RBCs), fresh frozen plasma (FFP), and IV/oral vitamin K1 as first-line therapy. Further evaluation varies according to the situation.
Warfarin and superwarfarin ingestions generally are acute or chronic. In either situation, determine whether the ingestion was unintentional 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 emergency department (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 K1 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 PT is elevated, treatment with vitamin K1 is appropriate. Ten milligrams orally is a reasonable daily dose. Since the pharmacologic effects of warfarin wear off within days, otherwise healthy patients with acute warfarin ingestions do not need supplemental vitamin K1 for more than several days. In the setting of superwarfarin-induced coagulopathies, 50-200 mg daily is recommended, and the duration of therapy may be many weeks.
Note that if a patient has a critical need for ongoing anticoagulation (eg, mechanical heart valve), heparin can be given as a temporary measure while the effects of warfarin are fully reversed.
Chronic intoxication resulting from the therapeutic use of warfarin can be evaluated with a careful physical examination and a measurement of the PT and INR.
Chronic ingestions of rodenticide superwarfarin may also be intentional (eg, Munchhausen syndrome) or can occur in the setting of child abuse (Munchhausen by proxy). These patients should be admitted for psychiatric or protective services evaluation.
If the INR is higher than therapeutic levels but less than 5 and the patient is not bleeding, withhold warfarin for 2-3 days and restart when the INR approaches the therapeutic range. If the patient requires more rapid reversal (eg, elective surgery), administer 1-2.5 mg of vitamin K1 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 5 but less than 9 and the patient is not actively bleeding, withhold warfarin for the next 1 or 2 doses, monitor the INR more frequently, and resume therapy at a lower dose when the INR is at the therapeutic level.
Another therapeutic approach would be to withhold 1 dose of warfarin and orally administer vitamin K1, 1-2.5 mg, particularly if the patient is at increased risk of bleeding. For more rapid reversal (eg, urgent surgery), administer vitamin K1, 2.5-5 mg, orally (expected reduction of the INR should occur in about 24 h).
If the INR is higher than 9 and the patient is not bleeding, a higher daily dose of oral vitamin K1 (5-10 mg) may be administered. In the setting of superwarfarin-induced coagulopathies, 50-200 mg is recommended.
Treatment of serious hemorrhage
Active, serious hemorrhage should be treated with FFP. This therapeutic strategy immediately restores therapeutic levels of coagulation factors. A volume of 15 mL/kg is typically sufficient to completely reverse coagulopathy.
Alternatively, recombinant factor VIIa (rFVIIa) or prothrombin complex concentrate, human (Kcentra) may be used. While costly, an essential advantage these therapies confer to emergency care is that, in contrast to FFP, they do not require thawing or blood group typing. Additionally, they have reduced risk of volume overload, transfusion-related acute lung injury, transfusion reactions, and infectious disease transmission. Despite these advantages, no mortality benefit has been proven for rFVIIa or PCC compared with FFP.
Administer vitamin K1, 10 mg, by slow IV infusion. Using IV vitamin K1 is rarely associated with acute cardiovascular collapse (probably an anaphylactoid response) in a small group of patients.
Consultations and Transfer
Since most warfarin and superwarfarin exposures result in minor or no significant effects, regional poison control centers can aid in decreasing the referral of patients to health care facilities and in reducing the performance of unnecessary laboratory tests in minor, unintentional 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 unintentional 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.
If the patient has any type of hemorrhage that the current facility is not capable of managing appropriately, transfer to a higher level of care is indicated.
Patients who are already on warfarin, who have had an unintentional overdose, and who are hemodynamically stable with no evidence of active bleeding can follow up with their regular source of anticoagulation care.
The frequency of routine INR monitoring for patients on stable warfarin dosing may be able to be extended further than every 4 weeks, depending on future studies.
Children with acute unintentional ingestions can be discharged home with follow-up care by their pediatrician in the office or by telephone at 48 hours. Most authorities no longer recommend routine follow-up PT measurement, because the incidence of significant anticoagulation in children after accidental exposure is extremely low.[8, 17, 18]
Anderson IB. Warfarin and related rodenticides. Olson KR. Poisoning and Drug Overdose. 5th ed. Appleton & Lange; 2007. 379-381.
Su M, Hoffman RS. Anticoagulants. Goldfrank's Toxicologic Emergencies. 8th ed. McGraw-Hill; 2006. 887-902.
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. [Medline].
Olmos V, Lopez CM. Brodifacoum poisoning with toxicokinetic data. Clin Toxicol (Phila). 2007. 45(5):487-9. [Medline].
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. [Medline].
Mowry JB, Spyker DA, Brooks DE, McMillan N, Schauben JL. 2014 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 32nd Annual Report. Clin Toxicol (Phila). 2015 Dec. 53 (10):962-1147. [Medline]. [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. [Medline].
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. [Medline].
[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].
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. [Medline].
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. [Medline].
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. [Medline].
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. [Medline].
Chua JD, Friedenberg WR. Superwarfarin poisoning. Arch Intern Med. 1998 Sep 28. 158(17):1929-32. [Medline].
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. [Medline].
Mullins ME, Brands CL, Daya MR. Unintentional pediatric superwarfarin exposures: do we really need a prothrombin time?. Pediatrics. 2000 Feb. 105(2):402-4. [Medline].
Smolinske SC, Scherger DL, Kearns PS, et al. Superwarfarin poisoning in children: a prospective study. Pediatrics. 1989 Sep. 84(3):490-4. [Medline].
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. [Medline].
Deveras RA, Kessler CM. Reversal of warfarin-induced excessive anticoagulation with recombinant human factor VIIa. Ann Intern Med. 2002. 137(11):884-888. [Medline].
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. [Medline].
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. [Medline].
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. [Medline].
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. [Medline].
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. [Medline].