Site-specific modifications and toxicity of blood substitutes: The case of diaspirin cross-linked hemoglobin

Safe and effective hemoglobin-based blood substitutes may be advantageous over conventional therapies for certain clinical settings requiring short term blood replacement such as emergency resuscitation and hemodilution in surgery. Many advances have been made in developing these oxygen therapeutics, however safety concerns continue to slow their clinical progress. An important and often overlooked consideration in evaluating the safety of modified hemoglobins is the impact of chemical and/or genetic modifications on the redox chemistry of these proteins. Diaspirin cross-linked hemoglobin (DBBF-Hb) has been extensively evaluated in vitro and in animal models, and thus represents a useful model to explore possible correlations between structural-functional alterations and toxicity of hemoglobin-based blood substitutes.