Blood Substitutes

Blood Substitutes The search for the perfect substitute for human blood began as early as the 17th century, when water, oil, milk and animal blood were used for transfusion until the first human-to-human transfusion in Philadelphia in 1795 (McCarthy 2003). Successes were, however, inconstant since then, as patients died due to injuries or from reactions to foreign blood, so that it was only a last resort during emergencies.

Early in the 20th century, the cataloguing of blood types enabled the matching of blood types between donors and recipients, despite the risk of blood infected with HIV and other viruses, drugs and toxins (McCarthy). Even then, there have been too few donors in proportion to a large number who require it. In 2000, for example, eight million donated 13 million liters and 4.5 received the donated blood. Supply has not only remained short of the need, the shelf life is also short.

The shelf life of red blood cells, for example, is 42 days and given this shelf life, 3 to 8% of donated units are soon disposed into the incinerator (McCarthy). The ideal substitute for human blood has to be an oxygen-carrying volume expander without the characteristic antigenicity that will avoid immune reactions (Bartz 2002). It must have a stable shelf life and an intravascular half-life ranging from weeks to months, free of infecting agents and harmful effects, easy to produce in massive quantities and affordable to wide-scale users (Bartz).

Most potential users or recipients of blood substitutes are trauma victims who need a universal oxygen-carrying volume expander that will not require cross-matching. Blood substitutes, given their low viscosity, can also be used during cardiac procedures to reduce the amount of packed red cells, for the reperfusion of ischemic organs during strokes or myocardial infarction, as organ preservatives and to enhance the effectiveness of cancer radiotherapy (Bartz). The first blood substitute to be marketed was a mix of perfluorodecalin and perfluorotripropylamine, emulsified with Pluronic F-68 and was called Fluosol-DA.

It was manufactured by Green Cross Corporation of Japan (Bartz). Eventually, it proved ineffective in significantly improving oxygen delivery in arresting acute hemorrhage, had short and ineffective intravascular half-life, unstable temperature, low oxygen-carrying capacity and a poor shelf life (Bartz). Fluosol-DA also caused acute complement activation, uptake by the reticuloendothelial system and disruption of normal pulmonary surfactant as major adverse effects. Due to these, the product was confined to angioplasty techniques in the U.S. until Green Cross stopped manufacturing it in 1994.

Oxygent combines perfluorooctyl bromide and perfluorodecyl bromide, has a low-volatility PFC that uses egg yolk lecithin as emulsifiers and more stable at room temperature than Fluosol-DA. Its oxygen-carrying capacity is also four to five times greater than Fluosol-DA's and makes it more useful in preventing acute hemorrhage (Bartz). However, it needs a high amount of inspired oxygen in order to be effective, has an intravascular half-life of less than a day and is dose-dependent, according to Bartz.

Continued clinical trials of Oxygent showed that it is more effective in reversing transfusion problems than fresh blood and also delays the need for subsequent transfusions (Bartz). These clinical tests in the U.S., Canada and Europe also reported adverse effects, including a 20% drop in platelet count two or three days after receiving Oxygent and fever. Oxygent, nevertheless, appeared to reduce the need for packed red blood cells.

Another product is Hemopure, which is derived from the blood of slaughtered cattle, and manufactured by 10 companies, awaiting the approval of the Food and Drug Administration (McCarthy). These manufacturers assured the public that their cattle were clean of bacteria, viruses and pathogens, including mad cow, because they came from a managed herd in Michigan. So far, it has proved to be a suitable product.

It does not get stored in the kidneys and too negligible to trigger an immune response, stores at room temperature in light-proof pouches and has a shelf life of three years (McCarthy). With these qualities, Hemopure has developed a clinical reputation as Oxyglobin in the U.S. And Europe. In clinical trials, 96% of those who received it did not need red cell transfusions on the day after surgery and 60% relied on Hemopure after six weeks (McCarthy). It has been approved for use in South Africa.

Hemopure interacts beneficially with the red cell gas transport systems better than ordinary blood: blood plasma normally bars oxygen transfer and red cells can release oxygen only when in direct contact with the capillaries. But when hemoglobin is dissolved directly into the bloodstream, red cells can at once exchange oxygen with the plasma itself, and this is the case with Hemopure (Levine as qtd in McCarthy). Polyheme is made from pyridoxylated polymerized and outdated human blood and manufactured by Northfield Laboratories (Bartz). However, it confronts the problem of regional shortages.

Its intravascular half-life is 24 hours and shelf life is longer than a year if refrigerated. It also possesses favorable oxygen-carrying properties Randomized trials showed that it reduced the frequency and number of red blood cell transfusions (Bartz). It is currently being tested for the cure of acute blood loss. Polyethylene glycol or PEG is also being tested for beneficial use in cancer therapy to increase tumor oxygenation and enhance radiotherapy and chemotherapy (Bartz).

Manufactured by Enzon, the product is PEG-conjugated bovine hemoglobin, the advantage of which is that it can be readily.