History
The idea to use a blood substitute is old as well as human intention to resuscitate a life with transfusion of real blood. In the past, many but often obscure trials were conducted. One recommendation from Sir Christopher Wren (17th century) who suggested wine and opium as blood substitute . At the beginning of the 20th century, the development of modern transfusion medicine initiated through the excellent work of Landsteiner and co-authors opened the possibility to understanding the general principle of blood group serology. Simultaneously, significant progress was made in the fields of heart and circulation physiology as well as in the understanding of the mechanism of oxygen transport and tissue oxygenation. These two points paved the way for blood transfusion to become a standard part of medical treatment. Complexity of blood compatibility, lack of suitable anticoagulants and insufficient storage methods combined with a disproportion between demand and availability implicated just in early phase of transfusion medicine needs to find one universal blood substitute. The term "blood substitute" is a misnomer. Under the term blood substitute, we understand in first line the substitution of a) facility of red blood cells e.g. haemoglobin as oxygen carriers and b) volume substitution. More accurately the term means "red-cell substitutes" or solutions of “haemoglobin or non-haemoglobin based oxygen carriers”.
Restrictions in applied transfusion medicine especially in disaster situations such as World War Two lay the grounds for an accelerated research in the field of blood substitutes. Early attempts and optimism in developing blood substitutes were very quickly confronted with significant side effects which according to for that time actual level of knowledge and technology could not be promptly eliminated. Appearance of HIV and infection in the 1980s with consecutive public sensibilisation was the impulse necessary to improve blood safety but also renewed impetus for development of infection-safe blood substitutes. This situation was more intense with the advent of HCV and Creutzfeld-Jakob Disease which showed the absence of absolutely safe blood. The continuous decline of blood donation combined with the increased demand for blood transfusion (increased ageing of population, increased incidence of invasive diagnostic, chemotherapy and extensive surgical interventions, terror attacks, international military conflicts) and positive estimation of investors in biotechnology branch make for a very positive environment for further development of blood substitutes. At the end of 2003 and March 2004 news that a selected patients in the Stockholm’s Karolinska Hospital and in two trauma centres in San Diego received red blood cell substitute without serious adverse events effects was just one positive reflection of the described constellation.
Taking into consideration that blood was used as resuscitation fluid with the main goal of improving oxygenation, research interest was in first line to develop substitute which mimic oxygen-carrying capacity of haemoglobin. In addition, an ideal blood substitute was define as one 1.) that required no cross-matching or compatibility testing; 2.) with a long shelf life over a wide range of ambient temperatures; 3.) which exhibit a long intravascular half-life (over days and weeks) 4.) free of side effects and pathogens.
Up until now, two types of oxygen carriers have been established: Perfluorocarbon emulsion and haemoglobin-based oxygen carrier (HBOCs). According to literature a significant increase of published case reports in which HOBC’s were under different conditions applied was observed in the last few years.
Read more about this topic: Haemoglobin-based Oxygen Carriers
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