title: The clotting system - a major player in wound healing.
abstract: Wound healing involves a complex series of interactions between coagulation, inflammation, angiogenesis, and cellular migration and proliferation. Our laboratory has developed an excisional dermal wound model in mice in order to study some of these processes and to determine how coagulation defects affect wound healing. In contrast to wild type mice, haemophilia B mice typically show delayed healing, signs of bleeding into the wound, and significant wound expansion. The difference in wound size may result from limited fibrin deposition in haemophilic animals and the subsequent inability to anchor the platelet plug to the surrounding tissues, thus allowing wound expansion through oedema. Haemophilic mice also demonstrate impaired wound healing times. However, while pre-treatment with factor IX or human activated factor VII improves some wound characteristics in haemophilia B animals, the time to wound healing is still delayed and signs of ongoing bleeding are evident. Haemophilic mice also show a deficient initial inflammatory response and increased angiogenesis, which, in turn, leads to increased bleeding: in the absence of robust haemostasis, these fragile, newly sprouted vessels have a tendency to bleed. Taken together, these observations suggest that ongoing haemostasis is necessary for normal wound healing. If this is correct, then optimal wound healing in haemophilia would require therapy until at least the point that vessel formation is stabilized. The goal of such treatment would be to avoid a feedback cycle in which bleeding tends to lead to further bleeding. Once initiated, this cycle may be difficult to control.
authors: Division of Hematology/ Oncology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7035, USA. dmonroe@med.unc.edu
authors: Dougald M
authors: DM
authors: Monroe
authors: Maureane
authors: M
authors: Hoffman
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000502:physiology*; D004195:Disease Models, Animal; D005164:Factor IX / Q000627:therapeutic use; D015942:Factor VIIa / Q000627:therapeutic use; D002836:Hemophilia B / Q000188:drug therapy / Q000503:physiopathology*; D006487:Hemostasis / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D051379:Mice; D018919:Neovascularization, Physiologic / Q000502:physiology; D012867:Skin / Q000098:blood supply; D014945:Wound Healing / Q000502:physiology*
chemical_list: D005164:Factor IX; D015942:Factor VIIa