Abstract

BackgroundHaemolytic conditions may contribute to disease pathogenesis and severe clinical manifestations through the liberation of free haemoglobin (Hb) and production of toxic free haem. Thus, free Hb and haem should be associated with altered MetHb and COHb levels in malaria as in other conditions.MethodsThis study comprises data collected at three different sites: (i) a retrospective analysis of the first arterial blood gas result (ABGS) of any patient during 2010 at the University Hospital in Lisbon; (ii) a retrospective analysis of ABGS from patients with severe malaria admitted to the intensive care unit in Berlin, Germany; and (iii) a prospective study of non-invasive MetHb measurements in children with and without malaria in Lambaréné, Gabon.ResultsIn Lisbon, the mean MetHb level was 1.4% (SD: 0.5) in a total of 17,834 ABGS. Only 11 of 98 samples with a MetHb level of >3.0 referred to infections. COHb levels showed no particular association with clinical conditions, including sepsis. In 13 patients with severe malaria in Berlin, the mean MetHb levels on admission was 1.29%, with 1.36% for cerebral malaria and 1.14% for non-cerebral malaria (P > 0.05). All COHb measurements were below 2.3%. In Lambaréné, Gabon, 132 healthy children had a mean MetHb level of 1.57%, as compared to 150 children with malaria, with a value of 1.77% and 2.05% in uncomplicated and complicated cases, respectively (P < 0.01).ConclusionsThe data appears consistent with the methaemoglobin/haem hypothesis in malaria and sepsis pathogenesis. However, although MetHb was significantly different between healthy controls and children with malaria in Africa, the difference was rather small, also when compared to previous studies. Still, non-invasive bedside MetHb testing may warrant further evaluation as it could be a simple adjuvant tool for prognosis in resource poor settings.

Highlights

  • Haemolytic conditions may contribute to disease pathogenesis and severe clinical manifestations through the liberation of free haemoglobin (Hb) and production of toxic free haem

  • The results presented here appear to be more in line with a study of 5,322 arterial blood gas result (ABGS) measurements in 183 critically ill patients in New York, who reported a range of results from 0% - 4.8%; and which concluded that COHb levels did not seem to be clinically useful as marker of critical illness [27]

  • Data from this study still appear to be consistent with the central chain of events in the haemolysis/MetHb/ haem hypothesis, and they do not provide evidence to refute this hypothesis

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Summary

Introduction

Haemolytic conditions may contribute to disease pathogenesis and severe clinical manifestations through the liberation of free haemoglobin (Hb) and production of toxic free haem. Free Hb and haem should be associated with altered MetHb and COHb levels in malaria as in other conditions. Conditions which cause haemolysis and lead to free haemoglobin (Hb) appear to contribute to disease pathogenesis and often severe clinical manifestations, such as renal impairment, vascular disease or inflammation [1]. One would expect that the presence of free Hb and haem, as well as the increase of HO-1 should be associated with altered MetHb and COHb levels in malaria and possibly other severe infections. Three studies in malaria reported different MetHb levels as compared to controls, the magnitude of the difference as well as the observed values varied several-fold between studies [14,15,16]. As pointed out in these studies, COHb levels may be strongly influenced by external sources of CO, for example cooking fires or cigarette smoke, while MetHb levels ought to reflect closer the underlying haemolytic process [4]

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