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Title: Relationship of cell-free hemoglobin to impaired endothelial nitric oxide bioavailability and perfusion in severe falciparum malaria.
Authors: Yeo, Tsin W
Lampah, Daniel A
Tjitra, Emiliana
Gitawati, Retno
Kenangalem, Enny
Piera, Kim
Granger, Donald L
Lopansri, Bert K
Weinberg, J Brice
Price, Ric N
Duffull, Stephen B
Celermajer, David S
Anstey, Nicholas M
Affiliation: International Health Division, Menzies School of Health Research and Charles Darwin University, Royal Darwin Hospital, Darwin, NT 0811, Australia..
Issue Date: 15-Nov-2009
Citation: The Journal of infectious diseases 2009-11-15; 200(10): 1522-9
Abstract: Hemolysis causes anemia in falciparum malaria, but its contribution to microvascular pathology in severe malaria (SM) is not well characterized. In other hemolytic diseases, release of cell-free hemoglobin causes nitric oxide (NO) quenching, endothelial activation, and vascular complications. We examined the relationship of plasma hemoglobin and myoglobin to endothelial dysfunction and disease severity in malaria. Cell-free hemoglobin (a potent NO quencher), reactive hyperemia peripheral arterial tonometry (RH-PAT) (a measure of endothelial NO bioavailability), and measures of perfusion and endothelial activation were quantified in adults with moderately severe (n = 78) or severe (n = 49) malaria and control subjects (n = 16) from Papua, Indonesia. Cell-free hemoglobin concentrations in patients with SM (median, 5.4 micromol/L; interquartile range [IQR], 3.2-7.4 micromol/L) were significantly higher than in those with moderately severe malaria (2.6 micromol/L; IQR, 1.3-4.5 micromol/L) or controls (1.2 micromol/L; IQR, 0.9-2.4 micromol/L; P < .001). Multivariable regression analysis revealed that cell-free hemoglobin remained inversely associated with RH-PAT, and in patients with SM, there was a significant longitudinal association between improvement in RH-PAT index and decreasing levels of cell-free hemoglobin (P = .047). Cell-free hemoglobin levels were also independently associated with lactate, endothelial activation, and proinflammatory cytokinemia. Hemolysis in falciparum malaria results in NO quenching by cell-free hemoglobin, and may exacerbate endothelial dysfunction, adhesion receptor expression and impaired tissue perfusion. Treatments that increase NO bioavailability may have potential as adjunctive therapies in SM.
DOI: 10.1086/644641
Type: Journal Article
Subjects: Adult
Anemia, Hemolytic
Endothelium, Vascular
Malaria, Falciparum
Malaria, Vivax
Middle Aged
Nitric Oxide
Severity of Illness Index
Young Adult
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