Skin necrosis is a rare complication of warfarin therapy that occurs between the third and 10th days of treatment. The pathogenesis of warfarin-induced skin necrosis is attributable to the emergence of a transient hypercoagulable state. The condition most commonly involves skin areas with abundant subcutaneous adipose tissue such as the breasts, buttocks, abdomen, thighs, and the extremities. We report the case of an 83-year-old woman who developed bilateral medial canthal skin necrosis following initiation of warfarin therapy.
An 83-year-old white woman with a history of aortic valve disease, hypertension, and anemia was admitted for elective aortic valve replacement. Her ocular history was notable for glaucoma and macular degeneration in both eyes. Following surgery, she developed atrial fibrillation and started taking Lovenox (Sanofi-Aventis, Bridgewater, NJ) (30 mg every 12 hours), subsequently replaced by warfarin (4 mg every day), maintaining the international normalized ratio within the therapeutic range of 2.0 to 3.0. Seven days after initiating warfarin therapy, the patient developed bilateral periorbital ecchymoses with dark lesions on the medial aspect and similar skin lesions on the upper back and the right arm.
Ophthalmic examination disclosed visual acuity of 20/200 OU, moderate bilateral periorbital ecchymoses, and full-thickness necrotic lesions measuring 6 × 7 mm involving the medial canthal region (Figure). Anterior segment examination results were unremarkable. Funduscopy revealed extensive geographic atrophy in both eyes.
. Bilateral periorbital ecchymoses and area of skin necrosis with necrotic eschar involving the medial canthi induced by warfarin therapy.
A diagnosis of warfarin-induced skin necrosis was made. Warfarin therapy was discontinued, and treatment with fresh frozen plasma, vitamin K, and heparin was initiated. Local therapy included debridement of the necrotic tissue and topical bacitracin ointment. The periorbital lesions improved with demarcation of the necrotic areas within 5 days. At 2 months' follow-up, the lesions had healed with mild scarring.
Warfarin-induced skin necrosis was initially reported by Flood et al1 in 1943. The condition usually occurs within 10 days of the initiation of warfarin therapy. The lesions are initially erythematous, purpuric, and sharply demarcated. They may resolve spontaneously or progress to form hemorrhagic bullae with eventual necrosis. Eighty percent of lesions occur in the lower half of the body in areas with abundant adipose tissues, such as the thighs, breasts, abdomen, and buttocks. In our patient, necrotic lesions uncharacteristically affected the medial canthal region of the eyelids as well as the trunk and arm. The mechanism for the development of warfarin-induced skin necrosis involves an early decline in vitamin K–dependent coagulation factors with short half-lives, such as proteins C and S and factor VII, leading to a transient hypercoagulable state.2 The risk factors include high loading doses of warfarin, prior deficiencies of proteins C and/or S and antithrombin III, and mutations in the methylenetetrahydrofolate reductase gene.3 Histopathologic studies have demonstrated thrombosis of the subcutaneous and dermal vessels with a relative lack of inflammation.4 Small lesions heal by secondary intention, whereas large lesions require surgical intervention.
Correspondence: Dr Tabandeh, Wilmer Eye Institute, B-20, Johns Hopkins Hospital, 600 N Wolfe St, Baltimore, MD 21287-9248 (email@example.com).
Financial Disclosure: None reported.
Thank you for submitting a comment on this article. It will be reviewed by JAMA Ophthalmology editors. You will be notified when your comment has been published. Comments should not exceed 500 words of text and 10 references.
Do not submit personal medical questions or information that could identify a specific patient, questions about a particular case, or general inquiries to an author. Only content that has not been published, posted, or submitted elsewhere should be submitted. By submitting this Comment, you and any coauthors transfer copyright to the journal if your Comment is posted.
* = Required Field
Disclosure of Any Conflicts of Interest*
Indicate all relevant conflicts of interest of each author below, including all relevant financial interests, activities, and relationships within the past 3 years including, but not limited to, employment, affiliation, grants or funding, consultancies, honoraria or payment, speakers’ bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued. If all authors have none, check "No potential conflicts or relevant financial interests" in the box below. Please also indicate any funding received in support of this work. The information will be posted with your response.
Some tools below are only available to our subscribers or users with an online account.
Download citation file:
Web of Science® Times Cited: 1
Customize your page view by dragging & repositioning the boxes below.
Users' Guides to the Medical Literature
Users' Guides to the Medical Literature
All results at
Enter your username and email address. We'll send you a link to reset your password.
Enter your username and email address. We'll send instructions on how to reset your password to the email address we have on record.
Athens and Shibboleth are access management services that provide single sign-on to protected resources. They replace the multiple user names and passwords necessary to access subscription-based content with a single user name and password that can be entered once per session. It operates independently of a user's location or IP address. If your institution uses Athens or Shibboleth authentication, please contact your site administrator to receive your user name and password.