Blood substitutes: how close to a solution?

The term "blood substitute" is commonly misused when "red cell substitute" is meant. The ideal red cell substitute should deliver oxygen (O2), require no compatibility testing, cause few side effects, have prolonged storage qualities, persist in the circulation, and be available at reasonable cost. While no drug with all of these qualities is on the near horizon, several early generation red cell substitutes are approaching submission for licensure, at least for limited indications. Hemoglobin-derived red cell substitutes from human bovine and recombinant sources, as well as perfluorochemicals that dissolve O2, are in different stages of development. While each formulation has its own physical characteristics, biologic activities, and adverse reaction profile, all share one characteristic: The physiologic consequences of delivering O2 with small molecules is poorly understood, both accounting for problems seen in the clinical trials and providing therapeutic opportunities for the cancer patient. All the red cell substitutes in phase II trials have a life measured in hours and are unlikely to replace transfusions or drugs that stimulate erythropoiesis for chronic anemia, but they may play a role in cancer surgery, or even in radiation therapy, or in the management of cancer-related vascular occlusive syndromes.