O-raffinose-polymerised haemoglobin. A biochemical and pharmacological profile of an oxygen carrier

Abstract

Haemoglobin-based oxygen carriers (HBOCs) represent an interesting class of blood substitutes which are undergoing advanced clinical trials. The therapeutic goal of these compounds is to avoid or reduce blood transfusion in different surgical and medical situations of acute haemoglobin deficiency. Their main advantages include availability in large volumes, storage for prolonged periods, rapid administration (without typing and cross matching) and sterilisation by pasteurisation. Their main known disadvantages are reduced circulation half-life, haemodynamic and gastrointestinal perturbations, probably related to nitric oxide (NO) scavenging, free radical induction, and alterations of biochemical and haematological parameters (increases in liver enzymes levels, platelet aggregation). Cell-free o-raffinose cross-linked and oligomerised human haemoglobin (O-r-poly-Hb) (Hemolink, Hemosol, Canada) is a modified haemoglobin with molecular weight ranging from 32- > 500 kDa. Its affinity for oxygen appears lower than normal blood and an n (Hill coefficient) value of about 1 indicates a very low degree of co-operativity. Probably related to the low O2 affinity value and to the high molecular weight, O-r-poly-Hb has been shown to induce lesser haemodynamic perturbations than other first generation modified haemoglobins. This HBOC is in Phase III clinical trials in cardiac and orthopaedic surgery for perioperative haemodilution, at doses from 25 g (250 ml)-100 g (1000 ml).