Haemoglobin-based oxygen carriers and myocardial infarction

Abstract

The incidence of investigator diagnosed myocardial infarction (MI) is greater in patients treated with haemoglobin-based oxygen carriers (HBOCs) than controls. Clinical trials and literature pertaining to possible HBOC toxicity mechanisms have been analyzed in order to identify possible reasons for this imbalance. MI diagnosis is hampered by potential interference of troponin assays by haemoglobin, haemolysis and bilirubin. Nevertheless, insofar as the reported incidence correlates with actual occurrence, there is a positive relationship between MI and HBOC dose and size. Preclinical and clinical data suggest that direct cardiac toxicity and coronary vasoconstriction are unlikely. More probable are detrimental intravascular interactions between HBOCs and components of the coagulation cascade, particularly dysfunctional endothelium. Elucidation of mechanisms is impeded by a lack of clinical data. Measurement of relevant biomarkers would be extremely useful in this regard and in improving patient selection criteria. Conduct of clinical trials in carefully selected patient populations after the development of improved protocols for MI diagnosis, along with concomitant biomarker data collection, is recommended.

Keywords:

• Haemoglobin-based oxygen carriers
• myocardial infarction
• troponin
• vasoconstriction

Disclosure statement

The author is a consultant for Omniox, Inc., an early stage biopharmaceutical company developing new medicines for hypoxic diseases. No support was received from Omniox for the production of this manuscript.