The role of iron deficiency anaemia & connexin 43 in poor wound healing

• Main Author: Wright, J. A.
• Published: University College London (University of London) 2014
• Subjects: 617
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.634662

Background Patients with diabetes have a 10% life-time risk of developing diabetic foot ulceration (DFU). DFU is the commonest cause of severe limb ischaemia in the western world. In diabetes mellitus, anaemia is frequently unrecognized. Recently, cell-to-cell interactions, via gap-junctional communication have been shown to play a key role in the molecular biology of wound-healing. Gap-junction channels are assembled of transmembrane proteins called connexins (Cx). Over-expression of Cx43 in wounded skin is associated with both a direct negative effect on keratinocyte and fibroblast migration and delayed wound-healing. Aims The aim of this thesis was to examine the problem of anaemia in patients with poorly-healing DFU. Further, to investigate the prevalence and type of anaemia seen in the high-risk severe DFU patient group, and to determine the current service provision required. Finally, to gain further scientific understanding of the wound-healing process and roles of anaemia and Cx43. Findings In severe DFU patients, >75% have iron deficiency anaemia, although a significant spread of indices was observed. Functional Iron Deficiency (FID) was seen in 25.5%. With current clinical markers, it is incredibly difficult to determine causal relationships. An in-vivo full-thickness excisional wounding study demonstrated that Hb decline correlated with slower re-epithelialisation (p=0.0060). Full-thickness skin biopsies taken from severe limb ischaemia patients demonstrated abnormal histological features in association with increased epidermal Cx43 expression at the wound-edge. 80% of unwounded surgically-viable skin showed persistence of these abnormal features not previously described. Conclusion In severe DFU patients, a high incidence of anaemia and FID was observed Identification of anaemia, AID and FID in this patient group is necessary to assess the role of therapeutic strategies. This is the first detailed in-vivo histological study to demonstrate that iron-deficiency anaemia may play a role in delayed wound-healing. Abnormal Cx43 dynamics in severe limb ischaemia may also represent a novel future therapeutic target.