Modified hemoglobin blood substitutes: present status and future perspectives.

Biotechnological techniques of cross-linking and microencapsulation of hemoglobin result in blood substitutes that can replace red blood cells. Unlike red blood cells they can be sterilized by pasteurization, ultrafiltration and chemical means. This removes microorganisms responsible for AIDS, hepatitis, etc. Since they are free of red blood cell blood group antigens, there is no need for cross-matching or typing. This saves time and facilities and allows on-the-spot transfusion such as the infusion of salt solution. Furthermore, they can be stored for a long time. Hemoglobin for modification can be extracted from human red blood cells. Other sources of hemoglobin include bovine hemoglobin and recombinant human hemoglobin. Clinical trials are ongoing testing the possible uses of cross-linked hemoglobin in cardiac, orthopedic, trauma and other types of surgery. It is also being tested for the replacement of lost blood in severe bleeding due to trauma or other causes. Cross-linked hemoglobins are first generation blood substitutes that only fulfil some of the functions of red blood cells. New generations of more complete red blood cell substitutes are being developed. These include cross-linked hemoglobin-catalase-superoxide dismutase and microencapsulated hemoglobin-enzyme systems.