Hemoglobin-Based Oxygen Carriers: Brief History, Pharmacology and Design Strategies, Review of the Major Products in Clinical Trials, On-Going Studies, and Coagulation Concerns

ABSTRACT

Transfusion of erythrocytes (RBC) to treat acute or chronic anemia has significant drawbacks, given the risks of transfusion, volunteer donor requirements, limited supply with increasing demand, especially during a pandemic such as COVID-19, and erythrocytes are often unavailable in emergency situations or where blood is not an option. Significant research has been undertaken for almost 100 years to attempt to replicate the functions of RBCs with oxygen carriers/oxygen therapeutics based on hemoglobin. Oxygen carriers that have been evaluated are hemoglobin-based oxygen carriers (HBOCs). HBOCs utilize hemoglobin (Hb) to transport oxygen around the body. Blood transfusion may be critical therapy in hemorrhagic trauma, various pathologies both acute and chronic, and surgical interventions. It has some important goals the first and most important is to recover oxygen delivery to organs, additionally, when restoration of circulating blood volume is achieved, maintenance of adequate blood pressure to ensure enough blood flow to deliver the oxygen to the microcirculation and resolving oxygen debt. This chapter will review the history of HBOCs, discuss how HBOCs have been designed and how developed HBOCs differ from each other based on their pharmacology and physiology, highlight all major products to undergo human trials including one extensively studied product approved for human use in two countries (Hemopure), introduce newer products still under development, and finally present translational and clinical trials studying whether or not certain HBOCs may cause coagulation issues. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.