Abstract
If not cured promptly, tissue ischemia and hypoxia can cause serious consequences or even threaten the life of the patient. Hemoglobin-based oxygen carrier-201 (HBOC-201), bovine hemoglobin polymerized by glutaraldehyde and stored in a modified Ringer's lactic acid solution, has been investigated as a blood substitute for clinical use. HBOC-201 was approved in South Africa in 2001 to treat patients with low hemoglobin (Hb) levels when red blood cells (RBCs) are contraindicated, rejected, or unavailable. By promoting oxygen diffusion and convective oxygen delivery, HBOC-201 may act as a direct oxygen donor and increase oxygen transfer between RBCs and between RBCs and tissues. Therefore, HBOC-201 is gradually finding applications in treating various ischemic and hypoxic diseases including traumatic hemorrhagic shock, hemolysis, myocardial infarction, cardiopulmonary bypass, perioperative period, organ transplantation, etc. However, side effects such as vasoconstriction and elevated methemoglobin caused by HBOC-201 are major concerns in clinical applications because Hbs are not encapsulated by cell membranes. This study summarizes preclinical and clinical studies of HBOC-201 applied in various clinical scenarios, outlines the relevant mechanisms, highlights potential side effects and solutions, and discusses the application prospects. Randomized trials with large samples need to be further studied to better validate the efficacy, safety, and tolerability of HBOC-201 to the extent where patient-specific treatment strategies would be developed for various clinical scenarios to improve clinical outcomes.
Highlights
Tissue ischemia and hypoxia cause increased anaerobic metabolism, ion imbalance, mitochondrial uncoupling, activation of endothelial cells and various cell death programs, and pro-inflammatory immune responses [1, 2]
Author conclusion For patients with severe anemia who cannot be infused with red blood cells (RBCs), long-term use of HBOC-201 is a feasible and safe oxygen bridge
When blood transfusion is not an option, HBOC-201 can be used as a life-saving intervention for patients with severe anemia
Summary
Tissue ischemia and hypoxia cause increased anaerobic metabolism, ion imbalance, mitochondrial uncoupling, activation of endothelial cells and various cell death programs, and pro-inflammatory immune responses [1, 2]. In 2008, the meta-analysis of cell-free hemoglobinbased blood substitutes and risk of myocardial infarction (MI) and death by Natanson et al and related editorials have caused widespread controversy over the safety of clinical patients using HBOC-21 [9,10,11,12]. Related editorials suggested that the conclusions of this meta-study based on mixed studies at different levels must be treated with caution [10,11,12] They argued that the imminent risk of death due to low Hb outweighs the risk of HBOCs, so indiscriminately requiring suspension of all the HBOC trials could be fatal to these patients. HBOC-201 has been shown to be effective in increasing oxygen extraction and delivery to peripheral and central organs and improving tissue oxygenation in studies related to isovolumetric hemodilution [47,48,49,50,51].
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