Artificial Blood Types

PolyHeme HBOC from Northfield Labs
Photo courtesy Northfield Laboratories
PolyHeme HBOC from Northfield Labs
Until recently, most attempts to create artificial blood failed. In the 19th century, doctors unsuccessfully gave patients animal blood, milk, oils and other liquids intravenously. Even after the discovery of human blood types in 1901, doctors kept looking for blood substitutes. World Wars I and II and the discoveries of hepatitis and the human immunodeficiency virus (HIV) also raised interest in its development.

Pharmaceutical companies developed a few varieties of artificial blood in the 1980s and 1990s, but many abandoned their research after heart attacks, strokes and deaths in human trials. Some early formulas also caused capillaries to collapse and blood pressure to skyrocket. However, additional research has led to several specific blood substitutes in two classes -- hemoglobin-based oxygen carriers (HBOCs) and perflourocarbons (PFCs). Some of these substitutes are nearing the end of their testing phase and may be available to hospitals soon. Others are already in use. For example, an HBOC called Hemopure is currently used in hospitals in South Africa, where the spread of HIV has threatened the blood supply. A PFC-based oxygen carrier called Oxygent is in the late stages of human trials in Europe and North America.

The two types have dramatically different chemical structures, but they both work primarily through passive diffusion. Passive diffusion takes advantage of gasses' tendency to move from areas of greater concentration to areas lesser concentration until it reaches a state of equilibrium. In the human body, oxygen moves from the lungs (high concentration) to the blood (low concentration). Then, once the blood reaches the capillaries, the oxygen moves from the blood (high concentration) to the tissues (low concentration).

passive diffusion
Artificial blood takes advantage of passive diffusion, in which oxygen moves from an area of high concentration (the lungs) to an area of low concentration (the blood).

HBOCs
HBOC vaguely resemble blood. They are very dark red or burgundy and are made from real, sterilized hemoglobin, which can come from a variety of sources:

  • RBCs from real, expired human blood
  • RBCs from cow blood
  • Genetically modified bacteria that can produce hemoglobin
  • Human placentas
However, doctors can't just simply inject hemoglobin into the human bloodstream. When it's inside blood cells, hemoglobin does a great job of carrying and releasing oxygen. But without the cell's membrane to protect it, hemoglobin breaks down very quickly. Disintegrating hemoglobin can cause serious kidney damage.
  • For this reason, most HBOCs use modified forms of hemoglobin that are sturdier than the naturally-occurring molecule. Some of the most common techniques are:
    • Cross-linking portions of the hemoglobin molecule with an oxygen-carrying hemoglobin derivative called diaspirin
    • Polymerizing hemoglobin by binding multiple molecules to one another
    • Conjugating hemoglobin by bonding it to a polymer
    Scientists have also researched HBOCs wrap hemoglobin in a synthetic membrane made from lipids, cholesterol or fatty acids. One HBOC, called MP4, is made from hemoglobin coated in polyethylene glycol.

    HBOCs work much like ordinary RBCs. The molecules of the HBOC float in the blood plasma, picking up oxygen from the lungs and dropping it off in the capillaries. The molecules are much smaller than RBCs, so they can fit into spaces that RBCs cannot, such as into extremely swollen tissue or abnormal blood vessels around cancerous tumors. Most HBOCs stay in a person's blood for about a day -- far less than the 100 days or so that ordinary RBCs circulate.

    However, HBOCs also have a few side effects. The modified hemoglobin molecules can fit into very small spaces between cells and bond to nitric oxide, which is important to maintaining blood pressure. This can cause a patient's blood pressure to rise to dangerous levels. HBOCs can also cause abdominal discomfort and cramping that is most likely due to the release of free radicals, harmful molecules that can damage cells. Some HBOCs can cause a temporary, reddish discoloration of the eyes or flushed skin.

    HBOC and PFC size in comparison to an RBC
    Both HBOCs and PFCs are considerably smaller than red blood cells.

    PFCs
    Unlike HBOCs, PFCs are usually white and are entirely synthetic. They're a lot like hydrocarbons -- chemicals made entirely of hydrogen and carbon -- but they contain fluorine instead of carbon.

    PFCs are chemically inert, but they are extremely good at carrying dissolved gasses. They can carry between 20 and 30 percent more gas than water or blood plasma, and if more gas is present, they can carry more of it. For this reason, doctors primarily use PFCs in conjunction with supplemental oxygen. However, extra oxygen can cause the release of free radicals in a person's body. Researchers are studying whether PFCs can work without the additional oxygen.

    PFCs are oily and slippery, so they have to be emulsified, or suspended in a liquid, to be used in the blood. Usually, PFCs are mixed with other substances frequently used in intravenous drugs, such as lecithin or albumin. These emulsifiers eventually break down as they circulate from the blood. The liver and kidneys remove them from the blood, and the lungs exhale the PFCs the way they would carbon dioxide. Sometimes people experience flu-like symptoms as their bodies digest and exhale the PFCs.

    Oxygent, a PFC-based oxygen carrier
    Photo courtesy John B. Carnett /Popular Science
    PFC-based artificial blood made by Oxygent

    PFCs, like HBOCs, are extremely small and can fit into spaces that are inaccessible to RBCs. For this reason, some hospitals have studied whether PFCs can treat traumatic brain injury (TBI) by delivering oxygen through swollen brain tissue.

    Pharmaceutical companies are testing PFCs and HBOCs for use in specific medical situations, but they have similar potential uses, including:

    • Restoring oxygen delivery after loss of blood from trauma, especially in emergency and battlefield situations
    • Preventing the need for blood transfusions during surgery
    • Maintaining oxygen flow to cancerous tissue, which may make chemotherapy more effective
    • Treating anemia, which causes a reduction in red blood cells
    • Allowing oxygen delivery to swollen tissues or areas of the body affected by sickle-cell anemia
    Artificial blood is not without controversy. Next, we'll look at some of the issues surrounding its use as well as its future in medicine.