Potential clinical applications of recombinant human haemoglobin in blood conservation

Haemoglobin solutions have been tried as blood substitutes for decades with little success. Problems with early haemoglobin solutions include instability of the haemoglobin tetramer in the plasma, resulting in dissociation of the protein into dimers, as well as excessively high oxygen affinity for clinical oxygen transport capabilities. Newer haemoglobin solutions are currently under development and may prove adequate to transport oxygen while avoiding excessive toxicity. However, these compounds pose other difficulties, including a short plasma half-life and the potential for systemic hypertension due to nitric oxide binding. Several haemoglobin solutions are now undergoing human testing for potential clinical use. Haemoglobin can be harvested from outdated packed red blood cell units and chemically altered for use in clinical scenarios. Likewise, bovine haemoglobin may be obtained and modified for use as a blood substitute. While both these approaches may yield clinically useful oxygen carrying solutions, neither is completely free from infectious risk. The use of recombinant technology to produce a genetically altered haemoglobin from Escherichia coli allows avoidance of infectious risks and a functional haemoglobin which does not need further chemical modification. Use of this first generation of recombinant human haemoglobin as a blood substitute may be limited due to its short half-life of <12 hours, but clinical uses such as replacement fluid for acute normovolaemic haemodilution during the perioperative period may allow significant blood savings for patients and the potential to avoid patient exposure to allogeneic transfusions.