Elevated Exhaled Carbon Monoxide Concentration in Hemoglobinopathies and Its Relation to Red Blood Cell Transfusion Therapy

Abstract

In this study, the authors examined a possible role of measurements of end-tidal carbon monoxide (CO), corrected for inhaled CO (ETCOc), as a noninvasive screening tool for hemoglobinopathies and as an indicator for when transfusions would be required in patients receiving chronic transfusions. ETCOc measurements were obtained in subjects with sickle cell disease (n = 18), thalassemia (n = 21), and healthy controls (n = 62). ETCOc values less than 3 parts per million (ppm) yielded a positive predictive value of 93% and negative predictive value of 94% in identifying hemoglobinopathies. Subsequently, 7 subjects with thalassemia had laboratory parameters and ETCOc measured over 2 transfusion cycles. ETCOc values were 4.90 +/- 0.32 ppm (mean +/- SD), with 89% of values being above normal (>or=3 ppm). Pretransfusion ETCOc levels significantly correlated with pretransfusion reticulocyte count (r = .96, P <.001), but not with pretransfusion hemoglobin (r = .44, P = .16) or pretransfusion soluble transferrin receptors (sTfR, r = .52, P = .10). In conclusion, we found that patients with hemoglobinopathies have ETCOc values above the range for healthy controls and ETCOc measurements can be used as an adjunct to hemoglobin measurements to determine the proper timing of transfusions.

Hemolysis during and after 21 days of head-down-tilt bed rest

“…Expiratory CO has previously been used to measure the normal steady state of hemolysis as well as enhanced hemolysis in pathological conditions mainly in pediatric populations (Engstedt ; Sylvester et al (); James et al. ; Caboot et al. ; Shih et al.…”

“…In healthy adults,~2.5 9 10E11 new erythrocytes are produced and senescent erythrocytes are destroyed daily creating a steady state of heme degradation (Higgins and Mahadevan 2010). Expiratory CO has previously been used to measure the normal steady state of hemolysis as well as enhanced hemolysis in pathological conditions mainly in pediatric populations (Engstedt 1957;Sylvester et al (2005); James et al 2010;Caboot et al 2012;Shih et al 2014;Lal et al 2015;Lozar-Krivec et al 2016). Tidmarsh et al (2014) reviewed 13 studies that used endtidal CO as a marker of hemolysis and stressed for need for an accurate, sensitive, and reliable measurement device.…”

Inflammatory Markers: Exhaled Nitric Oxide and Carbon Monoxide During the Ovarian Cycle

“…Through induction of HO-1, endogenous CO production could be increased by hypoxia, heavy metals, heme, exogenous CO, pro-inflammatory cytokines, hyperglycemia and hormones [36], and endogenously generated NO [20]. Thus, ECO may serve as a marker in diabetes [37], cirrhosis [38] hemoglobinopathies [39] asthma [7], cystic fibrosis [8], bronchiectasis [9], and respiratory tract infections [10]. In our study, exhaled CO levels were high in the secretory phase, reaching their highest levels in the premenstrual phase.…”

Evaluation of a new end‐tidal carbon monoxide monitor from the bench to the bedside

“…As noted with previous breath CO measurement devices , an elevated ETCOc level could provide clinicians with a better understanding of the presence of haemolysis in infants and, by deduction, the presence of bilirubin elimination disorders when ETCOc levels are normal and total bilirubin levels are high. In the absence of reliable tests to diagnose neonatal haemolysis, nursery protocols have relied on tests, such as the direct antiglobulin (or Coombs’) test, reticulocyte count and serum haptoglobin, which are all invasive, not timely, require access to laboratory facilities and have poor specificities and sensitivities .…”

“…Elevated levels of end‐tidal carbon monoxide corrected for inhaled carbon monoxide (ETCOc) have been correlated with blood carboxyhemoglobin corrected for inhaled carbon monoxide (COHbc) and increased bilirubin production in both healthy newborn infants and those with haemolysis. Elevated bilirubin production has also been reported in infants born premature, born to mothers with diabetes, with bruising or birth trauma, with iso‐immune haemolytic disorders, such as maternal–fetal blood group incompatibilities with ABO, Rh, or other minor groups, glucose‐6‐phosphate dehydrogenase (G6PD) deficiency, structural and functional red blood cell abnormalities and perinatal sepsis . The 2004 American Academy of Pediatrics (AAP) guideline specifically recommends that ETCOc measurements be used to identify the presence of haemolysis in infants and their subsequent risk for hyperbilirubinemia based on observations that haeme degradation from senescing red blood cells leads to the equimolar production of carbon monoxide (CO) and bilirubin in the absence of exposure to high ambient CO or active tissue injury .…”