title: Treatment of chronic leg ulcers with topical activated protein C.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: Institute of Bone and Joint Research, Kolling Institute, University of Sydney, Sydney, Australia.
authors.forename: Kaley
authors.initials: K
authors.lastname: Whitmont
authors.forename: Ian
authors.initials: I
authors.lastname: Reid
authors.forename: Sara
authors.initials: S
authors.lastname: Tritton
authors.forename: Lyn
authors.initials: L
authors.lastname: March
authors.forename: Meilang
authors.initials: M
authors.lastname: Xue
authors.forename: Michael
authors.initials: M
authors.lastname: Lee
authors.forename: Greg
authors.initials: G
authors.lastname: Fulcher
authors.forename: Phil
authors.initials: P
authors.lastname: Sambrook
authors.forename: Eric
authors.initials: E
authors.lastname: Slobedman
authors.forename: Alan
authors.initials: A
authors.lastname: Cooper
authors.forename: Chris
authors.initials: C
authors.lastname: Jackson
mesh_terms: D000287:Administration, Topical; D000368:Aged; D001707:Biopsy, Needle; D002908:Chronic Disease; D003646:Debridement; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D007871:Leg Ulcer / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D011486:Protein C / Q000627:therapeutic use*; D018570:Risk Assessment; D012494:Sampling Studies; D012720:Severity of Illness Index; D017592:Skin Care / Q000379:methods; D016896:Treatment Outcome; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D011486:Protein C