Blood substitutes: why haven't we been more successful?

Trends Biotechnol. 2014 Apr;32(4):177-85. doi: 10.1016/j.tibtech.2014.02.006. Epub 2014 Mar 12.


Persistent safety concerns have stalled the development of viable hemoglobin (Hb)-based oxygen carriers (HBOCs). HBOCs have several advantages over human blood, including availability, long-term storage, and lack of infectious risk. The basis of HBOC toxicity is poorly understood, however, several mechanisms have been suggested, including Hb extravasation across the blood vessel wall, scavenging of endothelial nitric oxide (NO), oversupply of oxygen, and heme-mediated oxidative side reactions. Although there are some in vitro and limited animal studies supporting these mechanisms, heme-mediated reactivity appears to provide an alternative path that can explain some of the observed pathophysiological changes. Moreover, recent mechanistic and animal studies support a role for globin and heme scavengers in controlling oxidative toxicity associated with Hb infusion.

Keywords: Blood substitutes; Heme; Hemoglobin; Oxidative toxicity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Biotechnology
  • Blood Substitutes*
  • Heme
  • Hemoglobins
  • Humans
  • Models, Molecular
  • Oxidative Stress


  • Blood Substitutes
  • Hemoglobins
  • Heme