Plasma methemoglobin as a potential biomarker of anemic stress in humans

Abstract

Purpose Transfusion of allogeneic red blood cells (RBCs) is one of the main treatments of acute anemia secondary to blood loss and fluid resuscitation within the operating room. Decisions to transfuse blood are based largely on intermediate biological markers (hemoglobin, arterial oxygen saturation, blood pressure, heart rate) which may not accurately reflect inadequacy of tissue oxygen delivery.Based on experimental studies, we hypothesized that anemia-induced tissue hypoxia activates adaptive mechanisms which promote local vascular nitric oxide (NO) production to improve tissue perfusion and survival during acute anemia. Hemoglobin (Hb) oxidation to methemoglobin (MetHb) may be a byproduct of such local NO production. Therefore, we tested the hypothesis that MetHb is a biomarker of hypoxic-anemic stress during acute hemodilution associated with cardiopulmonary bypass. Methods With institutional ethics approval, routine laboratory arterial blood gas and co-oximetry values were obtained from 295 patients undergoing heart surgery during February 1 to September 30, 2010, and the values were assessed retrospectively. All samples with an arterial oxygen saturation value C90% were included (n = 1,421). The maximal change in Hb associated with hemodilution on cardiopulmonary bypass was determined within 48 hr of surgery (n = 180). A chart review was performed to determine the incidence of RBC transfusion and exogenous nitrate administration. All anonymous data were analyzed by linear regression to determine the relationship between Author contributions Gregory M.T. Hare designed the research, performed the research, contributed novel intellectual input, analyzed the data, and wrote the paper. Alexander Mu performed the research, contributed novel intellectual input, and analyzed the data. Alexander Romaschin designed the research, performed the research, contributed novel intellectual input, and analyzed the data. Nadine Shehata designed the research, performed the research, contributed novel intellectual input, and analyzed the data. W. Scott Beattie designed the research, performed the research, contributed novel intellectual input, analyzed the data, and wrote the paper. C. David Mazer designed the research, performed the research, contributed novel intellectual input, analyzed the data, and wrote the paper. Albert K.Y. Tsui contributed novel intellectual input, analyzed the data, and wrote the paper. RésuméObjectif La transfusion de globules rouges alloge´niques est l'un des principaux traitements de l'ane´mie aigues econdaire a`une perte sanguine et au remplissage liquidien en salle d'ope´ration. La de´cision de transfuser du sang repose essentiellement sur des marqueurs biologiques interme´diaires (he´moglobine, saturation en oxyge`ne du sang arte´riel, pression arte´rielle, fre´quence cardiaque) qui pourraient ne pas refle´ter avec pre´cision l'insuffisance d'apport d'oxyge`ne aux tissus. A`partir d'e´tudes expe´rimentales nous avons fait l'hypothe`se qu'une hypoxie tissulaire induite par l'ane´mie act...

Thermal stress altered growth performance and metabolism and induced anaemia and liver disorder in Labeo rohita

“…Previous researches suggest that oxidative stress (Sharma et al, ) and anaemia (Hare, Tsui, Crawford, & Patel, ) both caused elevation in methaemoglobin level in blood. Methaemoglobin delivers less amount of oxygen in tissue (Hare et al, ); thus, both the conditions of lower haemoglobin concentration and the formation of methaemoglobin may cause decline in oxygen supply (hypoxia) in fish. All data discussed above only from live fish samples.…”

Review article: Risks of anemia and related management strategies: can perioperative blood management improve patient safety?

“…These data included biomarkers of tissue hypoxia (systemic erythropoietin, cerebral near-infrared spectroscopy); microvascular oxyhemoglobin desaturation (altered plasma nitrite/nitrate ratios), and enhanced nitric oxide production and/or activation (plasma methemoglobin). 40,41 Prospective studies are currently underway to identify whether such biomarkers of anemia-induced tissue hypoxia can accurately predict adverse clinical outcomes. With these data in hand, trials can then be designed to identify patient-specific Hb thresholds for tissue hypoxia, and this approach can then be used to determine if specific treatments improve patient outcomes.…”

Tolerating anemia: taking aim at the right target before pulling the transfusion trigger

“…Tissue hypoxia related to varying levels of anemia may be manifest by biomarker stress signaling. It has been suggested that biomarkers of tissue hypoxia, signaling subsequent changes in hypoxic cellular response related to anemia, may be specific and dynamic enough to eventually provide optimal patient‐specific feedback indicating that the lower Hb threshold has been reached and a RBC transfusion may be indicated . There is additional evidence suggesting that the magnitude of Hb reduction associated with acute anemia may have organ‐specific effects; that is, sensitivity to the negative effects of anemia may vary by Hb threshold for different organs .…”

“…The current study by Hogervorst and colleagues complements findings from other investigations that may suggest that current guideline recommendations for Hb triggers may be set too low . Relative reductions in Hb might provide additional perspective from a clinical viewpoint.…”