Skin Necrosis in a Patient with Protein S Deficiency, Warfarin Anticoagulation, and Acute COVID-19 Infection: A Case Report

Abstract

Abstract Introduction/Objective Although thrombotic complications from COVID are well documented, the pathophysiology remains poorly understood, especially in patients with comorbid hypercoagulable risk factors and anticoagulant medication use. COVID has several dermatologic manifestations that may occur due to alterations in hemostasis. We present a case of skin necrosis in a patient with protein S deficiency, warfarin anticoagulation, and acute COVID infection. Methods/Case Report A 48-year-old female, BMI >50, heterozygous Protein S (PS) deficiency, Factor V Leiden, and history of recurrent venous thromboembolic events on warfarin, tested positive for COVID. Her only symptom was fatigue. Several days later, the patient developed painful ecchymoses and erythematous blisters on her breast, arm, and abdomen. Laboratory results showed INR 3.6, fibrinogen 675-1054 gm/dL, WBC 15k with absolute neutrophilia, and D-dimer 2274 ug/L DDU. The patient confirmed compliance with her maintenance warfarin dose. Biopsy showed thrombotic vasculopathy without leukocytoclastic vasculitis. Wound cultures were negative. Results (if a Case Study enter NA) NA. Conclusion The patient’s history and presentation were concerning for warfarin induced skin necrosis. However, the patient had taken warfarin for > 20 years and had an INR of 3.6 which substantiated that warfarin was not discontinued or missed. A retrospective review of INR results during acute COVID infection showed a decrease in time in therapeutic range and an increase in supratherapeutic INRs, suggesting COIVD patients may require decreased warfarin doses. Additionally, PS levels decline in patients with COVID; a similar effect is seen with HIV and Varicella infections. It is theorized that this may be mediated by an increase in C4b binding protein, an acute phase reactant that regulates the complement cascade and binds PS. With an infectious source ruled out and the patients’ known comorbid conditions, an acute exacerbation of the patients underlying hypercoagulable state is the likely driver of the patient’s skin necrosis with COVID as the probable precipitator. In summary, inherited and acquired hypercoagulable risk factors should be included in the differential diagnosis as a cause of skin changes in patients with COVID infection. Although histology may be helpful in diagnosing the cause of skin changes with COVID, laboratory results and clinical correlation are key in identifying a etiology.