Intense efforts have been made by both industry and academia over the last three\ndecades to produce viable hemoglobin (Hb)-based oxygen carriers (HBOCs), also known as ââ?¬Å?blood\nsubstitutesââ?¬Â. Human trials conducted so far by several manufactures in a variety of clinical indications,\nincluding trauma, and elective surgeries have failed and no product has gained the Food and Drug\nAdministration approval for human use. Safety concerns due to frequent incidences of hemodynamic,\ncardiac events, and even death led to the termination of some of these trials. Several second generation\nHBOC products that have been chemically and/or genetically modified (or in some cases ligated\nwith carbon monoxide (CO)) found a new clinical application in conditions as complex as sickle\ncell disease (SCD). By virtue of higher oxygen affinity (P50) (R-state), and smaller size, HBOCs may\nbe able to reach the microvasculature unload of oxygen to reverse the cycles of sickling/unsickling\nof the deoxy-sickle cell Hb (HbS) (T-state), thus preventing vaso-occlusion, a central event in SCD\npathophysiology. However, biochemically, it is thought that outside the red blood cell (due to frequent\nhemolysis), free HbS or infused HBOCs are capable of interfering with a number of oxidative and\nsignaling pathways and may, thus, negate any benefit that HBOCs may provide. This review discusses\nthe advantages and disadvantages of using HBOCs in SCD.
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