Blood substitutes: Basic science, translational studies and clinical trials
Jonathan S. Jahr
Abstract
This thesis presents work from five peer reviewed, indexed publications on blood substitutes. The major concept is to provide oxygen delivery to vital organs and tissues during haemorrhage, whether due to surgical bleeding, trauma or other acute anaemic situations where blood is either unavailable or not an option. Extensive research for 50 years has presented multiple candidates for such an oxygen therapeutic, yet none are currently available for human or veterinary use except for one product, approved in South Africa and Russia for human use and a similar product for veterinary use in the USA and EU. Haemoglobin-based oxygen carriers, derived from either outdated human erythrocytes or bovine haemoglobin collected during slaughter of cattle for food, are made following removal of the red cell coat, which causes antigenicity, cleaned for prions, viruses, bacteria, yeast, and parasites, then repolymerised or encased in a pegylated coat with polyethylene glycol. Various haemoglobin-based oxygen carriers have been evaluated from basic science models to translational platforms and on to extensive clinical trials, that either mimic haemorrhage, acute anaemia or oxygen deficit and have been studied in detail. My two publications, presented on basic science models, help to elucidate measuring circulating blood and plasma volume in a clinical setting with point of care monitors. One translational model follows that evaluates potential coagulation issues with the administration of haemoglobin-based oxygen carriers, which would be counterproductive, especially in a traumatic haemorrhage situation. Finally, I present my publication which summarises the largest Phase III clinical trial of a haemoglobin-based oxygen carrier, supplemented by a single site evaluation of its effect on platelet function.