title: Late failure of a split-thickness skin graft in the setting of homozygous factor V Leiden mutation: a case report and correlative animal model from the Wound Etiology and Healing (WE-HEAL) study.
abstract: We present the case of a 53-year-old Caucasian male smoker with remote history of left lower extremity deep venous thrombosis (DVT) and a strong family history of thrombosis, who presented to the Center for Wound Healing at MedStar Georgetown University Hospital with spontaneous left leg ulceration. Prothrombotic evaluation showed homozygosity for the factor V Leiden (FVL) mutation. Therapeutic anticoagulation was commenced with warfarin (Coumadin®) and the patient underwent successful debridement and Apligraf® followed by split-thickness skin graft (STSG) of two wounds. He had an uneventful postoperative course and on the 27th postoperative day the grafts were 95% intact. However, by postoperative day 41 there was 10% graft loss, and over the subsequent 2 weeks both grafts necrosed. On further questioning, it transpired that the patient had discontinued his warfarin on postoperative day 37 because he thought that it was no longer necessary. The patient is enrolled in the Wound Etiology and Healing (WE-HEAL) study, and at the time of the original graft, residual skin fragments from the STSG were transplanted onto a nude mouse for development of an animal model of wound healing. The mouse graft was successful and was harvested at postoperative day 87 for pathological examination. We review the mechanisms by which prothrombotic states, particularly FVL mutation, can contribute to skin graft failure and delayed wound healing. This case highlights the importance of considering prothrombotic conditions in patients with spontaneous leg ulcerations and the impact of therapeutic anticoagulation on healing. It further allows us to demonstrate the efficacy of the animal model in which residual fragments of STSG tissue are utilised for transplant onto nude mice for manipulation in the laboratory.
authors.affiliation: Division of Rheumatology, Immunology and Allergy, MedStar Georgetown University Hospital, Washington, DC, USA.
authors.forename: Victoria K
authors.initials: VK
authors.lastname: Shanmugam
authors.affiliation: Division of Rheumatology, Immunology and Allergy, MedStar Georgetown University Hospital, Washington, DC, USA.
authors.forename: Sean
authors.initials: S
authors.lastname: McNish
authors.affiliation: Center for Wound Healing, MedStar Georgetown University Hospital, Washington, DC, USA.
authors.forename: Joanna
authors.initials: J
authors.lastname: Duncan
authors.affiliation: Center for Wound Healing, MedStar Georgetown University Hospital, Washington, DC, USA.
authors.forename: Brandy
authors.initials: B
authors.lastname: Root
authors.affiliation: Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Tassi
authors.affiliation: Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Anton
authors.initials: A
authors.lastname: Wellstein
authors.affiliation: Department of Pathology, MedStar Georgetown University Hospital, Washington, DC, USA.
authors.forename: Bhaskar
authors.initials: B
authors.lastname: Kallakury
authors.affiliation: Center for Wound Healing, MedStar Georgetown University Hospital, Washington, DC, USA.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Attinger
mesh_terms: D020016:Activated Protein C Resistance / Q000150:complications* / Q000473:pathology; D000818:Animals; D003094:Collagen; D004195:Disease Models, Animal; D005165:Factor V / Q000235:genetics*; D006085:Graft Survival; D006801:Humans; D007871:Leg Ulcer / Q000209:etiology / Q000473:pathology / Q000628:therapy*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D016038:Skin Transplantation; D014945:Wound Healing
chemical_list: C117898:Apligraf; C095381:factor V Leiden; D005165:Factor V; D003094:Collagen
keywords: Animal model; Factor V Leiden; Hypercoagulable state; Leg ulcer; Prothrombotic state
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