title: Progressive improvement in wound healing with increased therapy in haemophilia B mice.
abstract: Previous work has shown that normalized haemostasis only at the time of an injury is not sufficient to promote optimal wound healing in haemophilia B (HB) mice. However, the duration of treatment required for optimal healing has not been established. The goal of these studies was to determine the effect of different durations of replacement or bypassing therapy [factor IX(FIX) or factor VIIa (FVIIa)] on wound healing parameters in a mouse model of HB. A dermal wound was placed on the back of HB mice. Animals were either untreated or pretreated and then subsequently treated for 3 days, 5 days, or 7 days with FIX or FVIIa. Wound area, time to wound healing, haematoma formation and iron deposition were measured. All treated animals showed shortened time to healing relative to untreated animals. Haematoma formation was prevented by treatment and bleeding into the wounds, measured by iron scores, was reduced by treatment. In addition, there was a progressive improvement in healing with 7 days of treatment more effective than 5 days which was more effective than 3 days. Replacement therapy with FIX had slightly shorter healing times than bypassing therapy with FVIIa. HB mice treated with FIX had slightly smaller wound area than untreated animals; by contrast, FVIIa-treated animals had much smaller wound areas that were close to the wound areas seen in wild-type animals. The data suggest that sustained therapy is required for normal wound healing.
authors.affiliation: Division of Hematology/Oncology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Monroe
authors.forename: M
authors.initials: M
authors.lastname: Hoffman
authors.forename: H R
authors.initials: HR
authors.lastname: Roberts
authors.forename: U
authors.initials: U
authors.lastname: Hedner
mesh_terms: D000818:Animals; D003029:Coagulants / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005164:Factor IX / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D015942:Factor VIIa / Q000627:therapeutic use*; D006406:Hematoma / Q000517:prevention & control; D002836:Hemophilia B / Q000188:drug therapy*; D007501:Iron / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014945:Wound Healing
chemical_list: D003029:Coagulants; D005164:Factor IX; D007501:Iron; D015942:Factor VIIa
keywords: bleeding; factor IX; factor VIIa; haemophilia; mouse models; wound healing