Issues in the Development of Hemoglobin Based Oxygen Carriers

Hemoglobin based oxygen carriers (HBOCs) have been developed as alternative oxygen transporting formulations for the acute treatment of anemia and ischemia. Efficacy has been demonstrated in a variety of preclinical models and selected human patients; however, a higher overall incidence of mortality and myocardial infarction in those dosed with HBOCs in later stage clinical trials has prevented widespread regulatory approval. Diagnosis of myocardial infarction is confounded by the fact that HBOCs interfere with troponin assays, as well as other clinical chemistry measurements. Analysis of data pertaining to potential toxicity mechanisms suggests that coronary vasoconstriction is an unlikely contributor, but promotion of intravascular thrombosis may occur by several mechanisms. In addition, fluid and anemia management in patients infused with HBOCs has been suboptimal. Elucidation of potential toxicity mechanisms, refinement of use protocols, and definition of improved patient inclusion/exclusion criteria remain active areas of inquiry in understanding the best manner in which to utilize HBOCs.