Blood On Tap: Part 1: History in the Making

Both sides agree that dumping large amounts of saline into a patient until their blood resembles watered-down cherry Kool-Aid is ineffective at best, and a better solution would be a welcome change. Enter the age of oxygen therapeutics.

Blood Simple

In a sample tube, blood seems deceptively basic. When it's spun in a centrifuge, some of blood's true complexities begin to emerge. The blood will divide into three distinct bands. The pale yellow band at the top is plasma, the viscous glue that holds the suspended components of blood together. Plasma carries proteins, electrolytes, lipids and carbohydrates through the vascular system, playing a critical role in regulating pH, osmotic pressures and glucose levels. The thin intermediary layer is a collection of platelets and white cells. These are our clotting factors and immunity, respectively. The thick, dark layer across the bottom is made up of red cells; within each red cell is the chemically complex protein molecule known as hemoglobin.

It is this complex nature of blood that causes scientists to shudder at terms like "artificial blood." We have never come close to synthetically duplicating all of blood's unique properties and functions and most believe we never will. Products like Hemopure, Polyheme and Oxygent earn the title "oxygen therapeutic" because they attempt to duplicate one critical function of blood: the transport of oxygen to the cells and waste gases away from them. At present, the scientific community is divided into four distinct schools of thought regarding where to find a surrogate for hemoglobin's unique abilities.

Expired Human Blood

Large amounts of the nation's blood supply expire before they can be used. These expired lots are purchased from the American Red Cross and other donation centers and harvested for their hemoglobin. One unit of hemoglobin can be produced from every two units of discarded whole blood. Polyheme is an example of an expired human blood product.

Proponents of this technique feel that there will always be a ready supply of unused red blood cells, especially from plasma centers that pay for donations. Some critics are not as confident that dependence on human donors is a good long-term solution.

They point out that the final product lacks 2,3 DPG, a molecule necessary for human blood to off-load oxygen at the cellular level. Some feel the lack of 2,3 DPG in expired human blood products may make the end product less effective.

"This gets into an interesting physiologic discussion on the role of oxyhemoglobin affinity," says Dr. Gould, who is quick to refute the oft-heard claim. "There is no DPG in Polyheme, so we use PLP (pyridoxal phosphate), an organic phosphate that works like DPG. However, DPG has a temporary effect and PLP has a permanent effect, so I think the argument is overstated. Polyheme is very effective at oxygen unloading. Perhaps more so than red cells."

Bovine Hemoglobin

Cattle 18 months old and younger are maintained in controlled environments where everything they are exposed to is rigorously monitored. These cows become the donors of bovine hemoglobin. Hemopure is an example of a harvested bovine hemoglobin product.

Critics are leery about the possibility of disease transmission from donor cows to the final human recipients, but advocates for this technique feel that bovines are a more stable, controlled and reliable source of blood products than humans. As Thomas Moore, president and CEO of Cambridge, MA-based Biopure Corporation, likes to point out, "We know where our cows have been on Saturday night." They also emphasize that these products will not be subject to the demand shortages that our current blood supplies experience.

Another huge selling point for bovine hemoglobin products is their long-term stability at room temperature. Hemopure can be stored for years at room temperature, and has remained chemically unchanged through freezing and boiling tests, a serious advantage for future prehospital and military users.

Recombinant Hemoglobin