Resolution of Intractable Leg Ulcers Associated with Antiphospholipid Syndrome (APS) with Prophylactic Dose of Aspirin (ASA) and Enoxaparin: A Case Report

Background: Lower extremity ulcers are one of the most common skin manifestation in patients (pts) with APS, observed in 20-30% of pts. These skin ulcers typically respond poorly to conventional treatment. Although incompletely understood, the pathogenesis of the skin ulcers (and most of the clinical manifestations of APS) appears to be the result of vascular endothelial damage at the microcirculation level, leading to intracapillary thrombosis and focal inflammation. Systemic treatments with immunomodulatory agents such as glucocorticoids, intravenous immunoglobulin (IVIG) and immunosuppressants have been reported to improve outcomes, but typically carry substantial side-effects, and may not be available outside specialized referralcenters. The use of anticoagulation, with or without immunosuppression, in pts with APS and skin ulcers has been reported with variable results. Our group and others have documented an excellent safety profile with the combination of ASA 81 mg orally and enoxaparin 40 mg subcutaneously given to pregnant patients with APS and recurrent pregnancy loss. Patient with APS appear to share similar microcirculatory changes in the organs involved.

Methods: Case report.

Results: A 72 year-old gentleman was diagnosed with APS in 2000, when he was evaluated for recurrent deep venous thrombosis in the lower extremities, and was found to have a positive lupus anticouagulant serum test. He received anticoagulation with warfarin, with a target International Normalized Ratio (INR) of 2.5-3.5. In 2011, the patient was evaluated for full-thickness ulceration of the bilateral medial distal legs. He had been treated years earlier with venous ablation, and screening for lower extremity arterial insufficiency showed adequate peripheral circulation. The ulcers were treated with moist antimicrobial wound dressings, serial wound debridement, ongoing compression therapy, and a course of skin substitute therapy. After over one year of treatment the ulcers healed. Over the next several years the patient experienced several episodes of re-ulceration of the lower extremity ulcers despite continued use of compression stockings. He was treated in the same fashion, and each episode of re-ulceration required months of therapy to achieve healing. In mid-2017 he developed another episode of re-ulceration. Similar treatment was again initiated, with little improvement over the first several months of therapy. Physical findings and the recalcitrant nature of the ulcers suggested a direct casual relation with his underlying APS. Since our pt was not a candidate for any form of immunosuppression, he was started on daily subcutaneous enoxaparin 1 mg/kg and daily oral ASA 81 mg. A complete healing of the skin ulcers was noted three months after initiation of the above therapy. He continues on this treatment without any side-effects.

Conclusion: A multidisciplinary approach allows for a more detailed evaluation of these challenging cases and helps to improve clinical outcomes.