PO-0547High Extracellular Haemoglobin And Deficient Haemoglobin Scavenging - An Unrecognised Cause Of Pro-inflammation In Very Preterm Infants?

BackgroundExtracellular haemoglobin (Hb) is toxic and causal in pro-inflammation, oxidative stress and subsequent induction of down-stream mechanisms leading to cell death. Very preterm infants have low circulating levels of haptoglobin, the main endogenous scavenger of extra-cellular haemoglobin. Extracellular haemoglobin and its oxidised metabolite, methemoglobin (metHb), may be a principal inducer of pro-inflammation and oxidative stress leading to organ damage in very preterm infants.AimEvaluate the relationship between circulating levels of extracellular haemoglobin metabolites, endogenous haemoglobin-scavengers and markers of pro-inflammation.Material/methodsProspective study of 64 very preterm infants with a mean (SD) gestational age of 26.4 (1.9) weeks and birth weight of 888 (288) g. Concentrations of extracellular Hb and its metabolites (oxyhemoglobin, methemoglobin), haptoglobin, hemopexin, soluble CD163, TNFa, IL-1b, IL-6, IL-10, monocyte chemoattractant protein-1 (MCP-1) and MMP-9 were measured at 24 h of age through an indwelling arterial catheter. Iatrogenic hemolysis was carefully avoided during sampling and subsequent handling.ResultsMedian (range) concentrations of extracellular Hb were 145.4 (0.1-1718) microg/L, oxyHb 14.3 (5.6-156.3) mM, metHb 1.4 (0.1-31.5) mM, haptoglobin 34.4 (0.1-955) microg/L, hemopexin 0.25 (0.01-0.79) microg/L and CD163 0.7 (0.1-1.9) microg/L. There was an inverse correlation between levels of extracellular Hb and haptoglobin, (r= - 0.69 (p = 0.001)) and hemopexin (r=-0.64 (p = 0.001)). Incresed levels of metHb correlated with those of MCP-1 (r = 0.35, p = 0.01) and of TNFa (r = 0.30, p = 0.02).ConclusionVery preterm infants had high levels of extracellular Hb metabolites clearly overwhelming the endogenous haptoglobin scavenging system. Levels of the oxidised extracellular Hb metabolite, methemoglobin, correlated with markers of pro-inflammation. Supplementary treatment with a haemoglobin scavenger may be of importance in very preterm infants.