The demand for transfusions of blood products is rising as more complex surgeries are developed and more drastically ill patients are surviving longer. At the same time, the rate of blood donations is decreasing and there is a growing concern over the risk of infectious diseases such as hepatitis C and HIV/AIDS in the blood supply. In addition, blood has a relatively short shelf life, and significant costs associated with collecting, processing, and storing it. For these and other reasons, the search for suitable blood substitutes has been under way for many years.
There are two modalities of therapy used to treat significant blood loss: blood volume expanders and oxygen therapeutics. Blood volume expanders are further categorized as either crystalloid or colloid.
Crystalloid blood expanders are products such as Ringer’s lactate, physiologic saline, and D5W (dextrose,5%, in water). These products are good for replacing lost fluids quickly, but because of their osmotic properties and small particle size, don’t stay in circulation for long.
Colloid blood expanders are generally non-protein substances such as dextran, hydroxyethyl starch (HES), or gelatin based. These products have varying properties in terms of reactions with drugs that might possibly be administered at the same time, as well as differing efficacy and possible side effects.
Isoplasma is the product name of one of the colloid blood volume expanders. These products do not carry oxygen themselves. Instead, they are used with the aim of maintaining sufficient blood volume to allow the heart to continue circulating whatever red blood cells exist to carry oxygen.
In addition to the blood volume expanders, there is a group of products in use, or being developed, called oxygen therapeutics, which are intended to supplement the blood’s oxygen carrying capacity. These are also broken into two categories: perfluorocarbon (PFC) and hemoglobin based products.
PFCs are a hydrocarbon molecule product that has the ability to carry both oxygen and carbon dioxide, which is the job of red blood cells. However, the way PFCs carry these gasses is different. When PFCs are used, the patient must breathe a high concentration of oxygen to saturate the PFC molecules.
PFCs have been in use in some parts of the world since the late 1970s. One PFC product was approved by the FDA for use in the U.S. in 1990, but four years later, was pulled from use due to patient complications. Several PFCs are approved for use in other countries, and newly developed PFCs are currently in clinical trials.
Hemoglobin based oxygen therapeutics use the hemoglobin from human or animal red blood cells to carry additional oxygen. This may seem like an obvious solution to some, but using hemoglobin outside of red blood cells causes problems. Pure hemoglobin can cause severe kidney damage, and can increase the patient’s blood pressure and constrict blood vessels limiting blood flow. In addition, hemoglobin has poor oxygen capabilities when it is outside of red blood cells because the enzymes inside the red blood cell control how well the hemoglobin binds oxygen and how easily it releases it to needy tissues.
Companies working to develop hemoglobin based products have come up with ways to modify hemoglobin so that these problems are overcome. There are a handful of hemoglobin based products currently being developed and tested.
While there is currently no widely used blood substitute, the advantages of such a product are driving a significant amount of research activity. These advantages include universal compatibility, longer shelf life, greater availability, and products that are free of all infectious diseases. Many of the products being developed show promise and could one day be used as safe and effective red blood cell substitutes.
