Wound healing in haemophilia - breaking the vicious cycle

Our group has been studying how haemostasis interacts with repair processes and also how to optimize treatment of bleeding disorders in a mouse model of haemophilia B. We have found that cutaneous wounds heal more slowly in haemophilic mice than in wild‐type mice, and also exhibit histological abnormalities, even after closure of the skin defect. The haemophilic wounds showed reduced influx of inflammatory cells and increased angiogenesis. Even after surface closure, the haemophilic animals experienced repeated episodes of re‐bleeding and progressive accumulation of iron in the wound bed and deeper tissues. A dose of replacement or bypassing therapy sufficient to establish initial haemostasis did not normalize wound healing. In fact, daily dosing for 7 days was required to normalize wound closure. Thus, normal healing requires adequate haemostatic function for an extended period of time. We have hypothesized that this is because angiogenesis during healing predisposes to bleeding, especially in the setting where haemostasis is impaired. Thus, normalizing haemostasis, until the process of angiogenesis has resolved, may be required to prevent re‐bleeding and additional tissue damage.