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Hemoglobin solutions: use in surgical patients

Hemoglobin-based oxygen carriers (HBOCs) are solutions that can match the oxygen-carrying capacity of red blood cells (RBCs), and several HBOCs have reached advanced stages of development and clinical testing. One of the potential mechanisms by which HBOC solutions may be effective in reducing transfused blood may be a result of the fact that in hemorrhagic conditions, replenishing lost iron is difficult. Although the oxygen-carrying capacity of most HBOC solutions may be quite transient, they are rapidly metabolized, and free iron is potentially scavenged by multiple mechanisms to subsequently stimulate erythropoiesis and reticulocytosis. Unfortunately, diaspirin-linked HBOC solutions reported a higher mortality in trauma patients. Regrettably, the trauma patient population is a heterogeneous group of patients and, similar to therapeutic trials in sepsis, trauma patients represent a group with an extremely high morbidity and mortality incidence that can potentially complicate interpreting data.

Bovine hemoglobin represents an interesting alternative because of its availability and large quantity. A 500-kg steer has approximately 35 l blood with 12 g/dl hemoglobin (total-body hemoglobin content 4.2 kg), and bovine blood is available as an unlimited supply. Hemopure, a bovine product, is approved for veterinarian use in the United States, and for humans in South Africa. Multicenter, randomized, phase III, controlled trials have demonstrated the safety and efficacy of HEMOPURE® (Biopure Corporation), also known as HBOC-201. The product is ultrapurified to remove any plasma proteins, RBC stroma, and potential pathogenic material. During the manufacturing process, cross-linking and polymerization stabilize the hemoglobin molecule, which increases its vascular persistence as well as the efficiency of oxygen transport to tissue.

Results from clinical trials indicate that HBOC-201 can be used as an oxygen 'bridge' for patients experiencing anemia due to surgical blood loss until their own red blood cells are replenished. HBOC-201 is generally well tolerated and is approved for use in South Africa, where it is indicated for use in adult surgical patients who are acutely anemic and to eliminate, delay, or reduce the need for allogeneic RBCs. A Biologics License Application for HBOC-201 is currently under review by the United States Food and Drug Administration.

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Levy, J. Hemoglobin solutions: use in surgical patients. Crit Care 8 (Suppl 1), P127 (2004). https://doi.org/10.1186/cc2594

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