Blood Substitute - History

History

After William Harvey discovered blood pathways in 1616, many people tried to use fluids such as beer, urine, milk, and animal blood as blood substitute. The demand for more blood substitutes began during the Vietnam War as wounded soldiers were unable to be treated at hospitals due to blood shortages.

Major worldwide blood shortages have led scientists to synthesize and test artificial blood. Infected blood is a major problem for many countries. Each year 10–15 million units of blood are transfused without being tested first for HIV and hepatitis. The second largest cause of new HIV infections in Nigeria comes from transfused blood. A major problem associated with donated blood is that after it is stored it loses nitric oxide and causes vasoconstriction for the recipient.

The first approved oxygen-carrying blood substitute was a perfluorocarbon-based product called Fluosol-DA-20, manufactured by Green Cross of Japan. It was approved by the Food and Drug Administration (FDA) in 1989. Because of limited success, complexity of use and side effects, it was withdrawn in 1994. However, Fluosol-DA remains the only oxygen therapeutic ever fully approved by the FDA.

In the 1990s, because of the risk of undetected blood bank contamination from AIDS, hepatitis C and other emergent diseases such as Creutzfeldt-Jakob disease, there was additional motivation to pursue oxygen therapeutics. Significant progress was achieved, and a haemoglobin-based oxygen therapeutic called Hemopure was approved for Phase III trial (in elective orthopedic surgery) in the U.S., and more widely approved for human use in South Africa.

In December 2003, a new haemoglobin-based oxygen therapeutic, PolyHeme, began field tests in a Phase III trial on emergency patients (in trauma settings) in the U.S. PolyHeme was the 15th experiment to be approved by the Food and Drug Administration since 1996. Patient consent is not necessary under the special category created by the FDA for these experiments. In late 2005, an independent panel verified, after the fourth and final review of 500 trauma patients enrolled in this study by that date, that no statistical evidence of safety concerns had arisen so far in the study. This study concluded in mid-2006 with final enrollment of 720 patients. Wired news reported that the trial failed when 47 of the 350 people given PolyHeme died compared to 35 deaths out of 363 in the control group. Debate exists as to whether or not the difference in the mortality rate is attributable to the small sample size. The fact that the experimental subjects did not give consent is a significant factor.

In 2010, Hard to Treat Diseases, Inc. (HTD) merged with an anonymous Canadian biotechnology company in hopes to enhance donated blood or hemoglobin based blood substitutes to have a shelf life of 42 days and higher levels of Nitric Oxide when packaged.