BLOOD SUBSTITUTES

There is a strong need for a blood substitute (red cell substitute or oxygen-carrying formulation) because of a lack of donors, time consuming blood type analysis and crossmatch tests, limitation on preservation time, immunomodulation to the recipient, and viral transmission.

Three major types of red blood cell substitutes are being developed. Modified (e.g., crosslinked) hemoglobin is being investigated as a potential product because of its high oxygen-carrying capacity and oncotic properties. Liposome encapsulated hemoglobin, which more closely resembles red blood cells, is another approach being pursued. A different approach involves the development of perfluorocarbon emulsions which have the ability to dissolve large quantities of oxygen. Though modified hemoglobin, liposome encapsulated hemoglobin and fluorocarbons individually have several advantages, they also have the following major disadvantages and drawbacks:

Modified hemoglobin is antigenic in the large dose and may cause allergic reaction, has high viscosity, and the in vivo stability of the crosslinks is not satisfactory, therefore causing breakdown products to be liberated in circulation. Liposome encapsulated hemoglobin has both production and physiological problems. The fluorocarbons, e.g., emulsion of octylbromide, are gradually removed from the circulation by uptake into the reticuloendothelial system (liver, spleen, etc.) and also cause substantial enlargement of the organs.

Under grants from the Heart Lungs and Blood Institute (National Institute of Health, DHHS), we explored a unique class of compounds which have capability of carrying oxygen. We synthesized fluorocarbons with water soluble groups. Being water soluble and oxygen carrying capability, they don’t require emulsification.

Additional information