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November 17, 2008

Treatment of Chronic Leg Ulcers With Topical Activated Protein C

Author Affiliations

Author Affiliations: Institute of Bone and Joint Research, Kolling Institute, University of Sydney, Sydney (Drs Whitmont, Tritton, March, Xue, Sambrook, and Jackson), Departments of Dermatology (Drs Whitmont, Tritton, Lee, and Cooper) and Endocrinology (Mr Reid and Dr Fulcher), Royal North Shore Hospital, St Leonards, and Anatomical Pathology, Symbion Health Laverty Pathology, North Ryde (Dr Slobedman), Australia.

Arch Dermatol. 2008;144(11):1479-1483. doi:10.1001/archderm.144.11.1479

Background  The treatment of skin ulcers frequently presents a management challenge. Nonhealing wounds with poor response to conventional wound management therapy represent a significant cause of disability, affecting approximately 1% of the global population. Activated protein C is a serine protease with anticoagulant, angiogenic, and anti-inflammatory properties that has shown efficacy in patients for the treatment of severe sepsis. We report 4 cases of nonhealing lower limb skin ulcers that were treated with activated protein C.

Observations  The study included 4 patients whose wounds were not improving despite standard wound treatment for 4 months or more. Activated protein C was applied topically to their wounds once weekly for 4 weeks. All 4 patients showed a rapid positive response to treatment that was maintained during a 4-month follow-up period. The treatment was well tolerated, with no remarkable adverse effects or complications.

Conclusions  Activated protein C can stimulate wound healing in patients with skin ulcers that are refractory to conventional wound-healing therapies. The likely mechanism of action is its recognized ability to stimulate angiogenesis and reepithelialization and to inhibit inflammation. Activated protein C has potential as a therapeutic option for patients with chronic skin ulcers.