eMedicine Specialties > Emergency Medicine > Toxicology

Toxicity, Warfarin and Superwarfarins: Follow-up

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

Follow-up

Further Inpatient Care

• All patients with signs of active bleeding or who are at significant risk of life-threatening hemorrhage require admission to the hospital.
• In addition, suicidal ingestions require psychiatric evaluation and observation for 36-48 hours to monitor for anticoagulation.

Further Outpatient Care

• Patients who are already on warfarin, who have had an accidental overdose, and who are hemodynamically stable with no evidence of active bleeding can follow up with their regular source of anticoagulation care. Recommendations from a recent article are listed in Treatment.
• Children with acute accidental 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.

Transfer

• 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.

Deterrence/Prevention

• Instruct regular users of warfarin in proper use of their medication and in problem-solving methods to avoid accidental overdose (eg, daily pillboxes). Generally, the primary care provider handles this.
• After acute ingestions by children, instruct parents to remove possible sources of intoxication (eg, poisons on the floor, under sink, in garage).
  

Complications

• Hemorrhagic complications, as described above, are the major concern.
• Skin necrosis, usually observed between the third and eighth days of therapy, is a relatively uncommon adverse reaction to warfarin.
  • When it occurs, it can be extremely severe and disfiguring and may require treatment through debridement or amputation of the affected tissue, limb, breast, or penis.
  • It occurs more frequently in women and in patients with preexisting protein C deficiency and, less commonly, in men and in patients with protein S deficiency. Patients initially become hypercoagulable because warfarin depresses levels of the anticoagulant proteins C and S more quickly than coagulant proteins II, VII, IX, and X.
  • Extensive thrombosis of the venules and capillaries occurs within the subcutaneous fat. Women note an intense, painful burning in areas such as the thigh, buttocks, waist, and/or breast several days after beginning warfarin; skin necrosis and permanent scarring may follow.
  • Immediate withdrawal of warfarin therapy is indicated. Heparin can be substituted safely for warfarin; however, treatment of patients who require long-term anticoagulant therapy remains problematic.
  • Restarting warfarin therapy at a low dose (eg, 2 mg) while continuing heparin treatment for 2-3 days may be reasonable. The dosage of warfarin can be increased gradually over several weeks.
• Warfarin crosses the placenta during pregnancy and has the potential to cause teratogenesis and bleeding in the fetus. Warfarin and other Coumadin derivatives cause an embryopathy commonly termed fetal warfarin syndrome (FWS). No data are available on whether superwarfarin compounds cross the placenta or are excreted in breast milk.²
  • During the first trimester, particularly during weeks 6-12 of gestation, embryopathy caused by exposure and characterized by nasal hypoplasia with or without stippled epiphyses (chondrodysplasia punctata) may occur.
  • CNS abnormalities, including dorsal midline dysplasia characterized by agenesis of the corpus callosum, Dandy-Walker malformation, and midline cerebellar atrophy have been reported.
  • Ventral midline dysplasia, characterized by optic atrophy and eye abnormalities, has been observed.
  • Seizures, deafness, blindness, and mental retardation can occur in any trimester.
  • Spontaneous fetal abortion and stillbirth are known to occur, and an increased risk of fetal mortality is associated with warfarin use.
  • Although rare, other teratogenic reports following in utero exposure to warfarin include urinary tract abnormalities (eg, single kidney), asplenia, anencephaly, spina bifida, cranial nerve palsy, hydrocephalus, cardiac defects and congenital heart disease, polydactyly, deformities of toes, diaphragmatic hernia, corneal leukoma, cleft palate, cleft lip, schizencephaly, and microcephaly.
  • The effects of anticoagulation on the fetus are a particular concern during labor, when the combination of the trauma of delivery and anticoagulation may lead to bleeding in the neonate.
  • A few small studies have used warfarin in pregnancy after the 12th week of gestation, but these studies are insufficient to recommend the use of warfarin in the pregnant patient. Thus, do not administer warfarin during pregnancy.
• Other adverse reactions that occur infrequently with chronic warfarin therapy include agranulocytosis, alopecia, anaphylactoid reactions, anorexia, cold intolerance, diarrhea, dizziness, elevated hepatic enzyme levels, exfoliative dermatitis, headache, hepatitis, jaundice, leukopenia, nausea and/or vomiting, pruritus, and urticaria.
• Rare events of tracheal or tracheobronchial calcification are reported in association with long-term warfarin therapy. The clinical significance is not known. Priapism is associated with anticoagulant administration; however, a causal relationship with warfarin is not established.

Patient Education

• For excellent patient education resources, visit eMedicine's Drug Overdose Center and Poisoning - First Aid and Emergency Center. Also, see eMedicine's patient education articles Poisoning, Drug Overdose, Activated Charcoal, and Poison Proofing Your Home.

Miscellaneous

Medicolegal Pitfalls

• Using IV vitamin K is associated with acute cardiovascular collapse (probably an anaphylactoid response) in a small group of patients; furthermore, it is not medically necessary because the effects of vitamin K take several hours. For immediate reversal of anticoagulation, use fresh frozen plasma.
• Failure to recognize a co-ingestion with another substance that can cause morbidity or mortality is a pitfall.

Special Concerns

• See Complications for discussion of complications associated with pregnancy.

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author, John C Stein Jr, MD, to the development and writing of this article.

• Search for CME/CE on This Topic »

• Toxicity, Lidocaine (Emergency Medicine)
• Toxicity, Mercury (Emergency Medicine)
• Toxicity, Fluoride (Emergency Medicine)
• Toxicity, Lead (Emergency Medicine)

• Poisoning Treatment
• Poisoning - First Aid and Emergency Center
• Poisoning Causes
• Drug Overdose Overview
• Drug Overdose Center
• Poisoning Overview
• Poisoning Symptoms
• Activated Charcoal
• Poison Proofing Your Home Introduction

• Serotonin Toxicity, ECG Abnormalities Seen With Escitalopram Overdose
• Dietary Supplement May Protect Against Acetaminophen-Induced Liver Toxicity
• "Substantial" Toxicity With Peginterferon Use: FDA Staff

• Tenofovir-associated Renal and Bone Toxicity
• EGFR-Targeted Therapies in Lung Cancer: Predictors of Response and Toxicity
• New Insight Into Epirubicin Cardiac Toxicity: Competing Risks Analysis of 1097 Breast Cancer Patients