The role of hemoglobin based blood substitutes in transfusion medicine.
A cell-free oxygen transporting blood substitute would obviate many of the current concerns about conventional red cell transfusion therapy. Moreover, a stable oxygen-carrying solution could have benefits and applications not possible with red cell transfusions, such as the treatment of acute hypovolemic shock in acute care settings, the treatment of patients such as Jehovah's Witnesses who refuse blood transfusions, the priming of blood oxygenation pumps, ex vivo organ perfusion prior to transplantation, and in vivo perfusion in order to enhance sensitivity to radiation therapy. Among potential blood substitutes that transport oxygen, attention has focused on perfluorocarbons and a variety of hemoglobin preparations, either in free solution or encapsulated into lipid vesicles. In the design and production of hemoglobin solutions the following criteria must be met: low toxicity and antigenicity; efficacy as a plasma expander; prolonged survival in the circulation; adequate oxygen carrying capability and efficient oxygen unloading to tissues; long shelf life. Extensive preclinical testing and recent clinical trials have been performed on human and bovine hemoglobin chemically crosslinked to present rapid leakage of hemoglobin through the kidneys. Bovine hemoglobin has intrinsically low oxygen affinity simulating that of human hemoglobin in red cells. An alternative and attractive strategy is the production of human hemoglobin in E. Coli, thus enabling appropriate genetic mutations to optimize function. These include creation of peptide linkers to enhance plasma survival and amino acid replacements that permit a finely regulated lowering of oxygen affinity.
Bunn
H F
HF
Harvard Medical School, Boston, MA, USA.
D000818:Animals; D030801:Animals, Genetically Modified; D001692:Biological Transport; D001802:Blood Substitutes; D001803:Blood Transfusion; D002417:Cattle; D004274:DNA, Recombinant; D006801:Humans; D010100:Oxygen / Q000493:pharmacokinetics*
D001802:Blood Substitutes; D004274:DNA, Recombinant; D010100:Oxygen