Warfarin induced skin necrosis (WISN) is a rare but important side effect of warfarin. Early diagnosis may lessen the amount of permanent tissue damage and can prevent progression to full thickness skin necrosis. So, physicians should be aware of such a complication. Screening for protein C or S or anti-thrombin deficiencies, or presence of anti-phospholipid antibodies before beginning warfarin therapy, could be helpful to avoid high levels of international normalized ratio (INR). Here, we report a 54-year-old man who presented to the emergency department with acral and penile gangrene following prolonged use of warfarin.

Mahdizadeh, Fatemeh

Safari, Saeed

English

Warfarin induced skin necrosis (WISN) is a rare but important side effect of warfarin. Early diagnosis may lessen the amount of permanent tissue damage and can prevent progression to full thickness skin necrosis. So, physicians should be aware of such a complication. Screening for protein C or S or anti-thrombin deficiencies, or presence of anti-phospholipid antibodies before beginning warfarin therapy, could be helpful to avoid high levels of international normalized ratio (INR). Here, we report a 54-year-old man who presented to the emergency department with acral and penile gangrene following prolonged use of warfarin

Mahdizadeh, F.

Safari, S.

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Concurrent Hand and Penile Gangrene following Pro-longed Warfarin Use; a Case Report

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Emergency. 2017; 5 (1): e71CASE REPORTConcurrent Hand and Penile Gangrene following Pro-longed Warfarin Use; a Case ReportFatemeh Mahdizadeh1, Saeed Safari2∗1. Department of Emergency Medicine, Ilam University of Medical Sciences, Ilam, Iran.2. Department of Emergency Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.Received: March 2017; Accepted: June 2017; Published online: 21 June 2017Abstract: Warfarin induced skin necrosis (WISN) is a rare but important side effect of warfarin. Early diagnosis may lessenthe amount of permanent tissue damage and can prevent progression to full thickness skin necrosis. So, physi-cians should be aware of such a complication. Screening for protein C or S or anti-thrombin deficiencies, orpresence of anti-phospholipid antibodies before beginning warfarin therapy, could be helpful to avoid high lev-els of international normalized ratio (INR). Here, we report a 54-year-old man who presented to the emergencydepartment with acral and penile gangrene following prolonged use of warfarin.Keywords: Warfarin; penile diseases; gangrene; anticoagulants; necrosis; extremities© Copyright (2017) Shahid Beheshti University of Medical SciencesCite this article as: Mahdizadeh F, Safari S. Concurrent Hand and Penile Gangrene following Prolonged Warfarin Use; a Case Report. Emer-gency. 2017; 5 (1): e71.1. IntroductionWarfarin is widely used as an anticoagulant agent. War-farin induced skin necrosis (WISN) is an uncommon but seri-ous condition, occurring in 1:10000 patients who receive thisdrug, with a female/male ratio of 1:4 (1). Skin necrosis hasbeen reported in 0.17% of patients affected with side effectsof warfarin (2, 3). The majority of cases present in the firstmonth of treatment, but late onset WISN may also occur upto 15 years after starting the treatment (4, 5). In this reportwe describe a patient who had developed late onset warfarin-induced skin necrosis, concurrently in acral and penile area.2. Case presentation:The patient was a 54-years-old male presented with pe-nis and right upper extremity pain, black discoloration andswelling for the past two days. The patient was a knownand treated case of deep vein thrombosis from 6 years be-fore and he was taking warfarin intermittently during thistime. He was opium addicted. The patient was a cachec-tic man. He was completely alert (GCS =15). On ar-∗Corresponding Author: Saeed Safari; Department of Emergency Medicine,Shohadaye Tajrish Hospital, Tajrish Square, Tehran, Iran. Tel: +989128251535;Email: safari266@gmail.comrival to the emergency department, pulse rate was 90 perminute, respiratory rate was 18 per minute, blood pressurewas 115/70 mmHg and body temperature was 37.8 ◦C. Dis-tal part (about one third) of his right forearm was swollen,tender and black discolored and a bulla around the wristwas seen. Right lower extremity was edematous. Distalpulses of lower limbs were palpable but diminished becauseof edema. Also the penis was extremely tender, swollen,erected and dark discolored. Figure 1 shows the patient’slesions. His primary lab results were as follows: WhiteBlood Cell=6500 cells/µL, Hemoglobin=6.8 gr/dL, Hemat-ocrit =20.3, Platelet=269000 cells/µL, Prothrombin Time (PT)=28 s, Partial thromboplastin time (PTT)=43 s, internationalnormalized ratio (INR)=4.6, Blood Urea Nitrogen=10 mg/dl,Creatinine=0.7 mg/dl, Calcium=8 mg/dl, Phosphorous=2.7mg/dl, Total Protein=3.9 mg/dl, Albumin=1.8 mg/dl, Aspar-tate Aminotransferase (AST)=16 U/L, Alanine Aminotrans-ferase (ALT)=13 U/L, Lactate Dehydrogenase (LDH)=429U/L, Creatine Phosphokinase (CPK)=83 U/L. HBs-Ag, HCV-Ab and HIV-Ab were all reported as negative. Ultrasonog-raphy of right hand revealed subcutaneous edema and fluidcollection. A hematoma was reported in dorsal area at thelevel of first metacarpophalangeal joint. Arterial and venousduplex of right upper extremity were normal. Also CT an-giography of aorta to distal of right upper limb was normalwithout cut off. Ultrasonography of testicles revealed rightThis open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0).Downloaded from: www.jemerg.comF. Mahdizadeh and S. Safari 2Figure 1: Patient’s lesions in the right upper and lower extremities as well as penis.extra-testicular hematoma, left atrophic testis and edema ofscrotum. Duplex of both testicles were normal. Warfarinwas discontinued and correction of coagulation tests wasdone by replacement of fresh frozen plasma and vitamin K.Also cefazolin was ordered intravenously every 8 hours and16-French foley catheter was fixed. Partial penectomy andurethroplasty of anterior duct was done approximately twomonths after admission and then amputation of right handabove the wrist was performed. Histological findings of por-tion of penile shaft confirmed subtotal necrosis and areas ofold and fresh hemorrhage and hematoma. The patient wasstable and discharged four days after surgery. Surgeons ad-vised him to follow up in clinic. In our patient neither anti-phospholipid antibodies nor low levels of protein C or S weremeasured and nor heparin induced thrombocytopenia (HIT)was considered.3. DiscussionWISN begins as localized paresthesia with an erythematousflush, progresses to petechial and hemorrhagic bulla andmay eventually result in full thickness necrosis (6). It usuallyinvolves areas with more subcutaneous fat content such asbreasts, thighs, and buttocks (5, 7). Although the pathogen-esis of the disease is still unknown, there were numerous re-ports of inherited or functional deficiency of protein C, pro-tein S or Factor V Leiden, antithrombin III, hyperhomocys-teinemia or in association with HIT and anti-phospholipidsyndrome. Another theory for explaining the pathophysiol-ogy of WISN is hypersensitivity reaction or a direct toxic ef-fect (1, 2, 8). Obesity, premenopausal age, viral infections,hepatic disease, and drug interactions are mentioned as pre-disposing factors (1). The lesions must be differentiated fromnecrotizing fasciitis, venous gangrene, decubitus ulcer, andhematoma that are more common (1, 2). WISN is usually di-agnosed clinically, based on patient’s symptoms, lesion ap-pearance and history of recent warfarin therapy (4). Deter-mining protein C and S levels for assessing predisposing fac-tors and skin biopsy can aid in diagnosis. Histology typicallyshows diffuse microthrombosis within dermal and subcuta-neous capillaries, venules and deep veins, with endothelialcell damage resulting in ischemic skin necrosis and red bloodcell extravasation (9). The lack of perivascular inflamma-tion and arteriolar thrombosis, differentiates WISN from thevasculitis (4, 9). Treatment includes discontinuing warfarin,although it has not been shown to alter outcome, startingheparin, administrating vitamin K, fresh frozen plasma (FFP)or pure activated protein C because of its low level. Long-term treatment includes local wound care and observationof the wound until healing. Skin grafting, surgical debride-ment and amputation may be necessary in severe limb gan-grene (4, 8). WISN should be suspected in all patients whoundergo over-warfarinization, even with an initially normalcoagulation profile. Prompt diagnosis and discontinuationof warfarin are crucial for the prognosis (1, 3). Necrosis maybe prevented by identifying high risk patients and avoidinghigh dose of warfarin in high risk patients (1, 10). Several rec-ommendations for preventing WISN have been advanced: 1)Heparin should be continued until the INR is near the ther-apeutic range as a result of the warfarin therapy and vitaminK dependent clotting factors have been consumed; 2) Stan-dard or low dose warfarin should be used instead of initiallarge loading doses; 3) A clinician should be cautious whenadvancing the dosage of warfarin (6).4. Conclusion:WISN, while rare, is an important complication followingwarfarin administration. Therefore, physicians should beaware. Screening for protein C or S or anti-thrombin defi-ciencies, or presence of anti-phospholipid antibodies beforebeginning warfarin therapy, avoiding high INR level and fi-nally, early diagnosis may lessen the amount of permanenttissue damage and can prevent progression to full thicknessskin necrosis.This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0).Downloaded from: www.jemerg.com3 Emergency. 2017; 5 (1): e715. Appendix5.1. AcknowledgementsThe authors would like to thank the emergency departmentstaff of Shohadaye Tajrish Hospital, Tehran, Iran.5.2. Authors contributionAll authors passed four criteria for authorship contributionbased on recommendations of the International Committeeof Medical Journal Editors.5.3. Conflict of interestNone.5.4. FundingNone.References1. Kakagia D, Papanas N, Karadimas E, Polychronidis A.Warfarin-induced skin necrosis. Annals of dermatology.2014;26(1):96-8.2. Chan Y, Valenti D, Mansfield A, Stansby G. War-farin induced skin necrosis. British Journal of Surgery.2000;87(3):266-72.3. Murad AA, Daly T, Mulligan N, Lenane P. Extensivewarfarin-induced skin necrosis successfully treated withnegative pressure wound therapy. BMJ case reports.2014;2014:bcr2013203510.4. Choudhary S, Madnani A, Singh A. Late onset Warfarininduced skin necrosis in human immunodeficiency virusinfected patient with pulmonary tuberculosis. Indianjournal of sexually transmitted diseases. 2013;34(1):47-9.5. Kozac N, Schattner A. Warfarin-Induced Skin Necrosis.Journal of General Internal Medicine. 2014;29(1):248-9.6. Alves D, Chen I. Warfarin-Induced Skin Necrosis. Hospi-tal Physician. 2002;38(8):39-42.7. Miura Y, Ardenghy M, Ramasastry S, Kovach R, HochbergJ. Coumadin necrosis of the skin: report of four patients.Annals of plastic surgery. 1996;37(3):332-7.8. Khalid K. Warfarin-induced necrosis of the breast:case report. Journal of postgraduate medicine.2003;50(4):268-9.9. Nazarian R, Van Cott E, Zembowicz A, Duncan L.Warfarin-induced skin necrosis. Journal of the AmericanAcademy of Dermatology. 2009;61(2):325.10. Pourdeyhimi N, Bullard Z. Warfarin-induced skin necro-sis. Hospital pharmacy. 2014;49(11):1044-8.This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0).Downloaded from: www.jemerg.com

Concurrent Hand and Penile Gangrene following Prolonged Warfarin Use; a Case Report

Warfarin induced skin necrosis (WISN) is a rare but important side effect of warfarin. Early diagnosis may lessen the amount of permanent tissue damage and can prevent progression to full thickness skin necrosis. So, physicians should be aware of such a complication. Screening for protein C or S or anti-thrombin deficiencies, or presence of anti-phospholipid antibodies before beginning warfarin therapy, could be helpful to avoid high levels of international normalized ratio (INR). Here, we report a 54-year-old man who presented to the emergency department with acral and penile gangrene following prolonged use of warfarin. </p

Fatemeh Mahdizadeh

Saeed Safari

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Concurrent Hand and Penile Gangrene following Prolonged Warfarin Use; a Case Report

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