Affiliation:
1. Department of Physiology, Anatomy & Genetics, University of Oxford, Oxford, UK
2. Evelina London Children’s Hospital, Neonatal Unit 6th Floor, North Wing, St Thomas’ Hospital, London, UK
Abstract
Abstract
Background
Mild hemolysis occurs physiologically in neonates, but more severe forms can lead to life-threatening anemia. Newborns in developing regions are particularly at-risk due to the higher incidence of triggers (protozoan infections, sepsis, certain genetic traits). In advanced healthcare facilities, hemolysis is monitored indirectly using resource-intensive methods that probe downstream ramifications. These approaches could potentially delay critical decisions in early-life care, and are not suitable for point-of-care testing. Rapid and cost-effective testing could be based on detecting red blood cell (RBC)-specific proteins, such as carbonic anhydrase I (CAI), in accessible fluids (e.g., urine).
Methods
Urine was collected from 26 full-term male neonates and analyzed for CAI using immunoassays (ELISA, western blot) and proteomics (mass spectrometry). The cohort included a range of hemolytic states, including admissions with infection, ABO incompatibility, and receiving phototherapy. Data were paired with hemoglobin, serum bilirubin (SBR), and C-reactive protein (CRP) measurements.
Results
Urine from a control cohort (CRP < 20 mg/L, SBR < 125µmol/L) had no detectable CAI, in line with results from healthy adults. CAI excretion was elevated in neonates with raised SBR (>125 µmol/L), including those qualifying for phototherapy. Newborns with low SBR (<125 µmol/L) but elevated CRP (>20 mg/L) produced urine with strong CAI immunoreactivity. Proteomics showed that CAI was the most abundant RBC-specific protein in CAI-immunopositive samples, and did not associate with other RBC-derived peptides, indicating an intravascular hemolytic source followed by CAI-selective excretion.
Conclusions
CAI is a direct biomarker of intravascular hemolysis that can be measured routinely in urine using non-invasive methods under minimal-laboratory conditions.
Publisher
Oxford University Press (OUP)
Reference28 articles.
1. Physiologic anemia of the newborn infant;O’Brien;J Pediatr,1971
2. Haemolytic disease of the newborn;Murray;Arch Dis Child Fetal Neonatal Ed,2007
3. Burden of severe neonatal jaundice: a systematic review and meta-analysis;Slusher;BMJ,2017
4. Neonatal jaundice: aetiology, diagnosis and treatment;Mitra;Br J Hosp Med (Lond),2017
5. Jr. Hemolytic anemia;Dhaliwal;Am Fam Physician,2004
Cited by
2 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献