Connect with this month's featured Advertisers:

Simply increasing blood supply is not an easy answer – aside from HIV, West Nile Virus, and Hepatitis C, numerous other diseases pose a threat to transfusion patients and limit the amount of blood donated. Also, storage requirements as well as the shelf life of blood make it very difficult to keep on hand. Consequently, if a suitable blood alternative can be established and approved, it could serve as a crucial, medical breakthrough of the century.

Currently, there are two main blood alternative types being studied and tested. While neither are true substitutes, as they do not contain antibodies and cannot sustain life for a long period of time (replacements are required every few hours), they can transport oxygen.4 The first type, a red matter, mimics hemoglobin, a protein in blood that carries oxygen. The other, a white substance called perfluorocarbon (PFC), is a liquid capable of moving dissolved oxygen. Unlike hemoglobin, these substitutes don’t chemically bind with oxygen, but liquefy the oxygen.

Hemoglobin products such as Hemolink by Hemosol Inc. and Hemopure, manufactured by Biopure, which is derived from cow’s blood, are both in phase III trials awaiting sufficient safety and efficacy trial data. One major benefit these products offer is they can be stored at room temperature for a lengthy shelf life of 12–36 months, whereas natural bloods can only survive a few weeks and must be refrigerated. Also of note, these substitutes offer a universal blood type match. The Biopure Corporation declares that Hemopure removes infectious agents to stay purified, and can oxygenate tissue three times faster than natural blood.5 Polyheme, manufactured by Northfield labs, is made from human red blood cells in an attempt to restore hemoglobin levels, as well as restore lost blood volume.

Oxygent, by Alliance, is a PFC in the phase II trial stage. Oxygent claims to deliver oxygen faster than human blood to cells at risk of acute tissue oxygen deficiency. Another PFC, Oxycyte, developed by Synthetic Blood International Inc., has properties believed to carry five times more oxygen than hemoglobin, and thus, results in a longer synthetic blood half-life. Still not U.S. Food and Drug Administration (FDA) approved, Oxycyte has performed well in trials and, according to professionals, can carry oxygen fifty times faster than normal, natural blood.6

These blood alternative products have multiple possible uses in a wide variety of situations, including organ packing, preservation, and transplant. Essentially "typeless," made up of predictable ingredients, and readily available, blood substitutes would be ideal in universal trauma situations, facilitating speed of administration by not requiring any previous blood type cross matching. Readily available, blood substitutes could serve as a model tool for disaster preparedness. Simply put, human donors cannot produce as much or quickly as synthetic blood manufacturers. Currently, in the U.S., trauma victims are not allowed to receive blood transfusions outside of an emergency department. This means that precious moments are wasted during transport, which can influence the difference between life and death. If approved for use, these products could be administered during transport, and additionally, do not require consent from the victim or any of the traditional tests that human blood must undergo. Further proposals for use include elective surgeries, anemia treatment, delivery of oxygen to ischemic tissues after strokes, post-angioplasty, sickle-cell anemia, and enhancing oxygen delivery to tumors.7 These synthetic products could also be used for those who refuse blood transfusions due to religious beliefs. Battlefield use is also under consideration since synthetic blood storage is much more convenient.

As mentioned earlier, the FDA has yet to approve the usage of any chemically produced and stabilized hemoglobin. The main problem remains that while these synthetic blood products seem to work the same and exhibit the same characteristics, they are really quite different products. Some are concocted with hemoglobin from animal sources (bovine-hemoglobin) while others are from human sources. Since there are no set standards in the manufacture of these substances, the FDA faces a challenge in measuring safety and efficiency.

Another roadblock in approval is the FDA’s insistence that these products be used solely in cases where there is no other alternative and the person is likely to die otherwise. If these products were approved, the FDA fears real human blood would be slowly completely replaced, which would be dangerous as there are long-term side effects to these synthetic products.8 So, while neither product has been approved for routine use in the U.S., the FDA has approved Hemopure for "compassionate" use in severe life-threatening cases, where the individual is unlikely to survive until they arrive at the emergency department.

Although these blood substitutes may seem like a godsend, safety issues will continue to cross critics’ minds. Exactly how safe are these alternatives? In December of 2006, the FDA refused to allow synthetic blood testing on civilian trauma patients to continue, following a basic code of ethics stating that the potential harm is not worth the potential good. Fluosol, the only FDA-approved blood substitute in the 1990s, was taken off the market in 1994 because of problems with defrosting the stored product. From the little testing that has been accomplished, serious resulting adverse events may include stroke, multi-organ failure, vasoconstriction, gastrointestinal side effects, pulmonary hypertension, myocardial infarction, and even death.9 Without long term testing, other health hazards are unknown.

In addition to safety, cost continues to be an issue. Advocates insist that costs associated with synthetic blood are in fact lower than with human blood, because fewer tests need to be conducted on patients, such as typing and cross matching. Nevertheless, the proof is in the price. Current costs of natural blood can run up to $200 per unit, but blood substitute prices can range up to $1,000 per unit.10 Professionals believe that over time, however, these prices may decrease, without the additional costs of collection, screening, administrative, and storage costs normally associated with traditional human blood. Also, once the products’ manufacturing becomes more streamlined, prices are expected to fall.

The number one reason, however, synthetic blood products continue to face roadblocks is due to the extreme amount of controversy surrounding the ingredients. As mentioned earlier, many of these substitute products come from cow-derived products, such as bovine- hemoglobin. With the recent outbreak of mad cow disease, selling a cow-derived product proves to be a damaging marketing factor.

Although these products haven’t been given the green light for usage in the U.S., Hemopure has been approved for use and is currently used in South Africa. (Although, due to its high price tag, usage is limited.) Currently BioPure Inc. has donated several units of Hemopure to South African hospitals in order to spread the word and also to gain valuable resources for clinical treatment data.11

References: