A 68-year-old white male with a history of Factor V Leiden, deep vein thromboses (DVT), pulmonary embolism (PE), atrial fibrillation, and hyperthyroidism on warfarin therapy for 12 years presented to the emergency department (ED) with acutely worsening, bilateral, black, necrotic ulcerations of his lower extremities with associated edema, purpura, and progressive sloughing of skin (Figure 1). He reported minor lacerations to his right leg three times in the month prior and began to notice edema with small ulcerations two weeks prior. The patient had been on 5mg of warfarin for 12 years with stable INR control and with no recent changes in medication regimen.
His initial presentation was concerning for vasculitis since antibiotics had not improved his lesions and there was no growth on tissue or blood cultures. Rheumatologic and infectious work-up was grossly negative with the exception of an elevated Streptolysin O Titer with normal C3, C4, Serum IgA. UA showed proteinuria, and urine microscopy demonstrated too many to count RBC, WBC, and granular casts. Doppler ultrasonography was negative for DVTs, and MRI showed superficial edema. Punch and excisional skin biopsies were inconclusive. Renal biopsy revealed fibrin clots in small arteries consistent with a hypercoagulable thrombophilic state. Immunofluorescence was negative for antibodies against IgG, IgA, IgM, C3, C1q, fibrin, albumin, and kappa or lambda light chains. TTE demonstrated mild to moderately dilated left and right ventricles, ejection fraction (EF) of 35%, global left ventricular (LV) hypokinesis, and mild aortic root dilation.
The patient was treated with discontinuation of warfarin therapy and wound care. His skin lesions gradually improved. Warfarin was permanently discontinued, and the patient was discharged on rivaroxaban with the diagnosis of atypical late-onset WISN complicated by Factor V Leiden likely triggered by an underlying infection. The patient continued wound care outpatient with significant improvement in his lesions over the next 4 months.
Discussion:
We have presented an atypical case of late-onset WISN in a patient with Factor V Leiden on warfarin therapy with renal involvement. To the best of our knowledge, only one prior case has documented late-onset WISN after more than 12 years of therapy. It is unclear if duration of warfarin therapy prior to symptom onset affects prognosis and resolution of lesions. Interestingly, WISN has been described in conjunction with cases of congestive heart failure (CHF) exacerbations. Our patient’s TTE revealed mild-moderately dilated left and right ventricles and EF 35%. This association requires further investigation in the future. There are currently no cases demonstrating WISN with renal involvement in the literature. It is unclear what the significance of these findings may be in our patient. Given the pro-thrombotic state of WISN, it is possible that other organs including the kidneys and heart may be affected similarly.
Conclusions:
This case highlights the importance of including WISN in the differential of any patient who presents on warfarin with skin lesions. In addition, WISN may occur at any time period after initiation of warfarin, possibly affecting other organ systems. Finally, novel anti-coagulants may serve as an appropriate alternative therapy after diagnosis.