Haemoglobin-based erythrocyte transfusion substitutes.

Concerns about the infectious and immunosuppressive risks of allogeneic blood products persist, and the increased disproportion of blood donation and consumption has reinforced the search for alternative erythrocyte transfusion strategies in recent years. With the absence of problems such as nephro-toxicity, increased colloid osmotic pressure and sudden renal clearance, modern haemoglobin based oxygen carriers (HBOC) have shown their effectiveness and tolerability in numerous animal and several clinical studies. HBOC can be infused without prior cross-matching and are now available as stable formulations with long shelf-life. Most clinical studies have been performed with human cross-linked haemoglobin (DCLHb) but all trials were stopped two years ago because of an increased mortality in two clinical trials in patients who received DCLHb after stroke and multiple injury shock. However, experimental trials in animals are in progress with DCLHb and recombinant human haemoglobin. In contrast, Phase III studies with polymerised bovine haemoglobin (HBOC-201) are finished or currently under evaluation showing that infusion of HBOC-201 can avoid or reduce allogeneic blood transfusion needs in specific peri-operative settings. As a consequence, HBOC-2001 was actually approved for treatment of peri-operative anaemia in elective adult surgical patients in South Africa. Other human or bovine haemoglobin solutions are currently being investigated in different clinical studies in cardiac surgery patients, sepsis and tumour patients. More recent investigations have shown that HBOC are not only simple erythrocyte transfusion substitutes but highly effective oxygen donators in terms of tissue oxygenation. HBOC open the door for a new therapeutic strategy: plasmatic oxygen delivery with physiological concentrations of inspired oxygen. In specific situations (e.g., ischaemia or arterial stenosis) HBOC have advantages over red blood cells because they can reach post-stenotic or poorly perfused tissues with the plasma stream, where erythrocytes are not able to pass. In addition to significant plasmatic oxygen transport, HBOC also enhance tissue oxygenation because of the facilitated oxygen release by HBOC and from remaining erythrocytes. Further studies will show, if the outcome of patients with impaired perfusion (e.g., stroke or myocardial infarction) can be improved by prophylactic or therapeutic application of HBOC. Whenever these formulations are globally launched, they will find differential indications as potent oxygen-delivering drugs in addition to the globally recognised goal of red cell substitutes in cases of bleeding.