Recent advances in the development of haemoglobin-based blood substitutes

The term 'blood substitute' is commonly used to describe products which can carry and deliver oxygen. These products are also referred to as 'oxygen carriers' or 'oxygen therapeutics'. Blood substitutes are a new generation of oxygen therapeutics and their introduction will redefine treatment approaches in a wide range of medical and surgical practices. There are two major classes of this new generation of oxygen therapeutics (1) modified haemoglobin solutions, referred to as haemoglobin-based blood substitutes (HBBS) and (2) perfluorocarbon emulsions. Tremendous progress has been made in the past four years with the development of HBBS. In comparison, not much progress has been made in the development of perfluorocarbons as oxygen carriers. In the present review we have limited our discussion to the development of HBBS. Several types of HBBS have been developed and are in different phases of clinical trials. Free haemoglobin has been crosslinked, conjugated, polymerised or encapsulated to prevent its dissociation into dimers. The stability and purity of HBBS are extremely important in overcoming most of the significant toxicities of these products. Commercial manufacturers have utilised better proprietary formulations and purification technologies, and HBBS developed by these organisations have demonstrated safety in both preclinical and clinical studies. Recent research activities suggest a broad range of therapeutic applications for these new generation of oxygen therapeutics, 'blood substitutes'. The introduction of HBBS in critical care medicine will introduce a new approach of not only improving perfusion, but delivering oxygen to tissues.