Newborn Screening for Sickle Cell Disease and Other Hemoglobinopathies: A Short Review on Classical Laboratory Methods—Isoelectric Focusing, HPLC, and Capillary Electrophoresis

Frömmel, Cornelius

doi:10.3390/ijns4040039

Cited by 31 publications

(27 citation statements)

References 28 publications

(47 reference statements)

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“…Newborn thalassemia screening can be achieved mainly on the separation and measurement of the hemoglobin fractions using high‐performance liquid chromatography (HPLC), capillary electrophoresis (CE), or isoelectric focusing (IEF) 7‐11 . All types of α‐thalassemia cause the formation of γ 4 (Hb Bart's) tetramers at birth, making it an ideal screening target and widely used 12,13 .…”

Section: Introductionmentioning

confidence: 99%

Application of an optimized interpretation model in capillary hemoglobin electrophoresis for newborn thalassemia screening

Zou

Huang

et al. 2021

Int J Lab Hematology

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Introduction Newborn screening is an important supplement to thalassemia control and prevention. Capillary electrophoresis (CE) technology has several advantages for thalassemia screening but with low sensitivity, especially for thalassemia carriers. This study aims to illustrate the application of an optimized interpretation model in newborn thalassemia screening by capillary hemoglobin electrophoresis. Methods Two thousand, two hundred fifty‐eight neonates selected from four regions in China were enrolled and were screened for α‐thalassemia and β‐thalassemia by capillary electrophoresis. Results were interpreted based on an optimized model integrated with multiple parameters. Molecular analysis was carried out in synchrony and used as the gold standard for the screening performance assessment. The consistency among different regions and thalassemia genotypes were also investigated. Results Among the 2258 neonates, 485 were identified to have a likely diagnosis of thalassemia, and 422 α‐thalassemia, 80 β‐thalassemia, and 21 α/β‐thalassemia cases were confirmed by molecular analysis, including 277 α‐thalassemia silent carriers, 135 α‐thalassemia trait carriers, 10 Hemoglobin H disease, and 80 β‐thalassemia trait carriers. The screening sensitivity, specificity, positive, and negative predictive value for α‐thalassemia and β‐thalassemia were 84.83%, 99.14%, 95.98%, 96.41%, and 88.75%, 98.73%, 76.34%, and 99.48%, respectively. The optimized interpretation model showed higher performance for thalassemia carriers, though some neonates with silent α‐thalassemia genotypes (‐α3.7/αα, ‐α4.2/αα, and αWSα/αα) and β‐28/βN genotype were still missed. The screening performance among different regions was comparable. Conclusions Capillary hemoglobin electrophoresis with the optimized interpretation model shows reliable performance for newborn thalassemia screening. It is applicable to large‐scale population screening.

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Section: Introductionmentioning

confidence: 99%

Application of an optimized interpretation model in capillary hemoglobin electrophoresis for newborn thalassemia screening

Zou

Huang

et al. 2021

Int J Lab Hematology

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“…For the distinction between FSA (HbS/β + thalassemia or HbS/β ++ thalassemia) and an HbS carrier, the relative quantification of HbA and HbS and the ratio between HbA/HbS are used. However, this approach bears the risk of false positive and false negative results as there is an overlap between HbS/β + thalassemia or HbS/β ++ thalassemia and a simple carrier state for HbS, especially in premature babies [15]. In our routine interpretation we use a cutoff of HbS/HbA = 2 to distinguish infants with severe HbS/β + thalassemia (i.e., FSa).…”

Section: Discussionmentioning

confidence: 99%

“…Numerous studies provide clear evidence that life-threatening early complications of SCD can be largely avoided if the diagnosis is made early, ideally in the first three to six months of life [15]. Introduction of NBS for SCD has significantly contributed to decreased morbidity and mortality among affected individuals.…”

Section: Introductionmentioning

confidence: 99%

The Alberta Newborn Screening Approach for Sickle Cell Disease: The Advantages of Molecular Testing

Zhou

Ridsdale

MacNeil

et al. 2021

IJNS

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Sickle cell disease (SCD), a group of inherited red blood cell (RBC) disorders caused by pathogenic variants in the beta-globin gene (HBB), can cause lifelong disabilities and/or early mortality. If diagnosed early, preventative measures significantly reduce adverse outcomes related to SCD. In Alberta, Canada, SCD was added to the newborn screening (NBS) panel in April 2019. The primary conditions screened for are sickle cell anemia (HbS/S), HbS/C disease, and HbS/β thalassemia. In this study, we retrospectively analyzed the first 19 months of SCD screening performance, as well as described our approach for screening of infants that have received a red blood cell transfusion prior to collection of NBS specimen. Hemoglobins eluted from dried blood spots were analyzed using the Bio-Rad™ VARIANT nbs analyzer (Bio-Rad Laboratories, Inc., Hercules, CA, USA). Targeted sequencing of HBB was performed concurrently in samples from all transfused infants. During the period of this study, 43 of 80,314 screened infants received a positive NBS result for SCD, and of these, 34 were confirmed by diagnostic testing, suggesting a local SCD incidence of 1:2400 births. There were 608 infants with sickle cell trait, resulting in a carrier frequency of 1:130. Over 98% of non-transfused infants received their NBS results within 10 days of age. Most of the 188 transfused infants and 2 infants who received intrauterine transfusions received their final SCD screen results within 21 ± 10 d of birth. Our SCD screening algorithm enables detection of affected newborns on the initial NBS specimen, independent of the reported blood transfusion status.

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“…In Europe, HPLC, capillary electrophoresis (CE), isoelectric focusing (IEF) and tandem mass spectrometry are recommended as appropriate methods for newborn screening for SCD [ 29 ]. Among these methods, HPLC, CE, and IEF have the ability to separate and precisely quantify hemoglobin fractions [ 30 , 31 ]. Therefore, these three methods are recommended as screening tests for SCT before high-risk surgeries.…”

Section: Discussionmentioning

confidence: 99%

Postoperative acute multiple organ failure after hepatectomy in a Nigerian male with sickle cell trait: a case report

et al. 2021

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Background Sickle cell disease (SCD) is a monogenic disease characterized by sickle hemoglobin (HbS). Patients homozygous for HbS experience symptoms resulting from sickled erythrocytes no later than adolescence. However, heterozygous HbS carriers, or those with the so-called sickle cell trait (SCT), may undergo surgery without their hemoglobinopathy being known. Case presentation A 53-year-old Nigerian male with hepatitis C infection underwent radiofrequency ablation therapy for multiple hepatocellular carcinomas (HCCs) 17 months prior. Follow-up computed tomography (CT) revealed a solitary tumor (3.2 cm) in the medial section of the cirrhotic liver. The Child–Pugh score was five, and the indocyanine green retention rate at 15 min was 17.4%. The nontumorous liver of the medial section accounted for 10% of the total liver volume according to CT volumetry. With the diagnosis of recurrent HCC, left medial sectionectomy was performed under intermittent blood flow occlusion by Pringle’s maneuver. Intraoperative ultrasonography confirmed that hepatic blood flow had been preserved after hepatectomy. However, laboratory tests on postoperative day (POD) 1 revealed severe liver damage: aspartate aminotransferase 9250 IU/L, alanine aminotransferase 6120 IU/L, total bilirubin 2.8 mg/dL, and prothrombin time% 20.9%. The patient’s renal and respiratory functions also deteriorated; therefore, continuous hemodiafiltration and plasma exchange were initiated under mechanical ventilation. Whole-body contrast-enhanced CT showed no apparent ischemia of the remnant liver, but diffuse cerebral infarction was detected. Despite intensive treatments, he died of multiple organ failure on POD 20. The pathological examination of the resected specimen revealed that the intrahepatic peripheral vessels were occluded by sickled erythrocytes. Additionally, chromatographic analysis of hemoglobin detected the presence of abnormal hemoglobin, although microscopic examination of the peripheral blood erythrocytes did not show morphological abnormalities. Based on these findings, we determined that he had SCT and developed vaso-occlusive crisis involving multiple organs just after hepatectomy. Conclusion SCD is a rare disease in eastern Asia, but its prevalence is increasing globally. Surgeons should pay increased attention to this disease, especially when performing hepatectomy under blood flow occlusion.

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Newborn Screening for Sickle Cell Disease and Other Hemoglobinopathies: A Short Review on Classical Laboratory Methods—Isoelectric Focusing, HPLC, and Capillary Electrophoresis

Cited by 31 publications

References 28 publications

Application of an optimized interpretation model in capillary hemoglobin electrophoresis for newborn thalassemia screening

Application of an optimized interpretation model in capillary hemoglobin electrophoresis for newborn thalassemia screening

The Alberta Newborn Screening Approach for Sickle Cell Disease: The Advantages of Molecular Testing

Postoperative acute multiple organ failure after hepatectomy in a Nigerian male with sickle cell trait: a case report

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