The attempt to develop a viable blood substitute spans more than 7 decades. These efforts have essentially focused on the ability of red blood cells to carry oxygen. Hence, most of the products that are in advanced-phase clinical trials are derivatives of hemoglobin and are known as hemoglobin-based oxygen carriers (HBOCs).
Today, an increase in the number of elective surgeries and the still prevalent but small risk of transmission of blood-borne pathogens such as HIV have served as a stimulus to develop a synthetic substitute for human blood, more specifically for development of a red blood cell substitute.
However, to date, no oxygen-carrying blood substitutes are approved for use by the US Food and Drug Administration. This fact highlights not only the challenges that exist in formulating an effective blood substitute but also the immense potential that exists in this field.
The physiology of oxygen transport can be described as follows:
One gram of adult hemoglobin binds to 1.39 milliliters of oxygen. The oxyhemoglobin dissociation curve (see the image below) has a characteristic sigmoid shape due to the cooperative effect that exists between the multiple oxygen binding sites on the hemoglobin molecule. Factors that modify the ability of hemoglobin to bind oxygen include body temperature, pH of blood and the concentration of 2,3-diphosphoglycerate (2,3-DPG).
The oxyhemoglobin dissociation curve plots the proportion of hemoglobin in its saturated form on the vertical axis against the prevailing oxygen tension on the horizontal axis. Image courtesy of Wikimedia Commons.