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Objective: The capillary zone electrophoresis (CZE) and highperformance liquid chromatography (HPLC) methods were compared in terms of HbA2 measurement for the assessment of hemoglobinopathies. Materials and Methods: CZE was compared with HPLC for the evaluation of patients without hemoglobinopathy (n=321), with β-thalassemia trait (n=113), and with common (HbD-Punjab, E, C, S/A, and S/S) and rare (HbS/D, O-Arap, Lepore, G-Coushata, Setif, Hamadan, Q-Iran, and H) variants (n=21). The reference range for HbA2 was determined by CZE. Results: Among patients without hemoglobinopathy, the median (2.5th-97.5th percentiles) values were 97.4% (97.0-98.0%) and 97.5% (96.6-98.4%) for HbA (p=0.060) and 2.4% (1.6-3.0%) and 2.5% (1.6-3.1%) for HbA2 (p<0.001) by HPLC and CZE, respectively. The reference range for HbA2 was 1.6-3.1% by CZE. In the comparison of methods for HbA2, there was a constant error of 0.255 (confidence interval: 0.062-0.448) and bias of 0.10% (limit of agreement: 0.33- 0.53), and higher values were obtained with CZE. A strong correlation was observed between the methods (r=0.782). Interrater agreement was almost perfect for clinical diagnosis (=0.911). The two methods detected and identified the common variants similarly. All rare variants, except HbH by HPLC and HbS/D by CZE, were detected as separate peaks by both methods. Conclusion: The two methods were in agreement regarding the preliminary identification of β-thalassemia patients. Different Hb variants were detected by both methods but with possible methodological interference for HbA2 measurements. CZE is a reliable and simple alternative for the evaluation of hemoglobinopathies. The standardization of HbA2 measurements should be prioritized as more techniques become available in routine laboratory practice [ABSTRACT FROM AUTHOR]

Cation exchange high-performance liquid chromatography (HPLC) is one of the techniques available for determining glycated hemoglobin (HbA1c) and also the method of choice for structural hemoglobinopathies screening. The objective of this case is to show how in a routine HbA1c test it is possible to incidentally find a hemoglobinopathy. In a routine blood analysis, an abnormal value for the hemoglobin A2 (HbA2) was obtained during the study of HbA1c with HPLC on the ADAMS™ A1c HA-8180T. After suspecting it could be due to the presence of a hemoglobinopathy, the study of possible variants was expanded using electrophoresis and HPLC on the Hydrasys and Variant II analysers, respectively. Since it could not be identified by these conventional methods, a genetic study was also carried out using Sanger sequencing. The patient presented a low HbA2 (1.3 %) and a 24.9 % variant with a retention time of 1.95 min, compatible with alpha-globin chain variant. In the genetic study, the pathogenic variant c.138C>G was detected in the HbA2 gene in heterozygosis, which resulted in the expression of the structural hemoglobinopathy known as hemoglobin Bari. The initial screening for structural hemoglobinopathies allows its identification or suspicion especially when it was performed with HbA1c analysis, requiring subsequent confirmation and diagnosis by other techniques. [ABSTRACT FROM AUTHOR]

Haemoglobinopathies constitute a large proportion of hemolytic anemias constituting around 74% of hereditary hemolytic anemias. Till date, about 200 alpha chain variants have been identified, one of which is Hb Fontainebleau. It is a rare alpha chain variant characterized by an Alanine → Proline substitution at codon 21 with a GCT>CCT change at the molecular level. It is incidentally detected on HPLC as an unknown peak. We present a case of Hb Fontainebleau in a 53-year-old male patient who presented with symptoms related to hemolytic anemia and an unknown peak on the HPLC chromatogram. [ABSTRACT FROM AUTHOR]

Hemoglobin disorders are among the most common genetic diseases worldwide. Molecular diagnosis is helpful in cases where the diagnosis is uncertain and for genetic counseling. Protein‐based diagnostic techniques are frequently adequate for initial diagnosis. Molecular genetic testing is pursued in some cases, particularly when a definitive diagnosis is not possible and especially for the purpose of assessing genetic risk for couples wanting to have children. The expertise available in the clinical hematology laboratory is essential for the diagnosis of patients with hemoglobin abnormalities. Initial diagnoses are made using protein‐based techniques such as electrophoresis and chromatography. Based on these findings, genetic risk to an individual's offspring can be assessed. In the setting of β‐thalassemia and other β‐globin disorders, coincident α‐thalassemia may be difficult to diagnose, which can have potentially serious consequences. In addition, unusual forms of β‐thalassemia caused by deletions in the β‐globin locus cannot be definitively characterized using standard techniques. Molecular diagnostic testing has an important role in the diagnosis of hemoglobin disorders and is important in the setting of genetic counseling. Molecular testing also has a role in prenatal diagnosis to identify fetuses affected by severe hemoglobinopathies and thalassemias. [ABSTRACT FROM AUTHOR]

* Context.--Underuse of laboratory testing has been previously investigated in preselected populations, such as documented malpractice claims. However, these numbers might not reflect real-life situations. Objective.--To evaluate the underuse and misuse of laboratory follow-up testing in a real-life hospital patient population with microcytic anemia, using laboratory results ordered during routine patient care. Design.--From all patients in whom a microcytic anemia was detected during routine diagnostics in 2018, all available laboratory data were collected and screened for appropriateness of diagnostic workup of iron deficiency and thalassemia. Subgroup analysis was performed for patient groups with mean corpuscular volume values 75 to 79 µm³ (group 1), 65 to 74 µm³ (group 2), and <65 µm³ (group 3). Results.--A total of 2244 patients with microcytic anemia were identified. Follow-up testing for iron deficiency was not performed in 761 cases (34%). For inconclusive ferritin levels due to elevated C-reactive protein results (n = 336), reticulocyte hemoglobin content or soluble transferrin receptor levels were missing in 86 cases (26%). In patients with suspected thalassemia (n = 127), follow-up testing for hemoglobin variants was not performed in 70 cases (55%). Subgroup analysis showed that the frequency of underuse of iron status as well as thalassemia/hemoglobinopathy testing decreased from group 1 to group 3. When considering relevant preexisting anemia diagnoses, laboratory tests were underused in 904 cases (40.3%). Conclusions.--Because 40% (n = 904) of the patients with microcytic anemia were potentially not followed up correctly, laboratory specialists are advised to act by implementing demand management strategies in collaboration with clinicians to overcome underuse of laboratory tests and to improve patient safety. [ABSTRACT FROM AUTHOR]

Objective: To report the diagnostic challenges of newborn screening for abnormal haemoglobins. Setting: Cord blood samples from 13 hospitals in southwest Jamaica taken in 2008–2019. Methods: Blood spots, collected from the umbilical cord, were analysed by high pressure liquid chromatography (HPLC) to reveal phenotypes for HbSS and HbCC, but genotype confirmation may require parental studies or gene sequencing. Such cases that were successfully traced were analysed in this follow-up study. Results: HPLC screening of 121,306 samples detected HbAS in 11,846 (9.8%), HbAC in 4508 (3.7%) and other electrophoretic abnormalities in 1090 babies. Among 101 previously unconfirmed cases, 34/90 (38%) with HPLC evidence of a HbSS phenotype had other genotypes, and 7/11 (64%) with a HbCC phenotype had other genotypes. Syndromes from the interaction of β thalassaemia occurred in 112 babies (85 with HbS, 27 with HbC) and of genes for hereditary persistence of fetal haemoglobin (HPFH) in 18 (12 with HbS, 6 with HbC). Variants other than HbS and HbC occurred in 270 babies, 16 in combination with either HbS or HbC, and 254 as traits. Most variants are benign even when inherited with HbS, although HbO Arab, HbD Punjab, or Hb Lepore Washington, which occurred in 6 cases, may cause sickle cell disease. Conclusions: Genes for β thalassaemia and HPFH are common in western Jamaica and when associated with HbS may present diagnostic challenges in newborns, as HbF and HbA2 have not reached diagnostic levels. Family and DNA studies may be necessary for genotype confirmation. [ABSTRACT FROM AUTHOR]

Hemoglobinopathies are the most common monogenic disorders in the world with an ever increasing global disease burden each year. As most hemoglobinopathies show recessive inheritance carriers are usually clinically silent. Programmes for preconception and antenatal carrier screening, with the option of prenatal diagnosis are considered beneficial in many endemic countries. With the development of genetic tools such as Array analysis and Next Generation Sequencing in addition to state of the art screening at the hematologic, biochemic and genetic level, have contributed to the discovery of an increasing number of rare rearrangements and novel factors influencing the disease severity over the recent years. This review summarizes the basic requirements for adequate carrier screening analysis, the importance of genotype–phenotype correlation and how this may lead to the unrevealing exceptional interactions causing a clinically more severe phenotype in otherwise asymptomatic carriers. A special group of patients are β‐thalassemia carriers presenting with features of β‐thalassemia intermedia of various clinical severity. The disease mechanisms may involve duplicated α‐globin genes, mosaic partial Uniparental Isodisomy of chromosome 11p15.4 where the HBB gene is located or haplo‐insufficiency of a non‐linked gene SUPT5H on chromosome 19q, first described in two Dutch families with β‐thalassemia trait without variants in the HBB gene. [ABSTRACT FROM AUTHOR]

Introduction: Hemoglobinopathies are major public health problems worldwide. Accurate laboratory diagnosis of the carrier is essential, which includes initial screening, Hb analysis, and DNA analysis. For the first time, we have developed a single‐tube quality control (QC) sample for these laboratory tests. Methods: The QC sample was made from a lyophilized mixture of the stabilized hemolysate with carbon monoxide saturation and the white blood cells of known thalassemia mutations. Homogeneity and stability were examined by Hb and DNA analyses on day 0 and every month for 12 months, at room temperature, 4°C, and −20°C. A preliminary proficiency testing (PT) program for hemoglobinopathies using this single QC material was developed. Results: Hemoglobin (Hb) and DNA analyses of a single‐tube QC sample demonstrated satisfactory results of Hb analysis for at least five months and DNA analysis for at least one year of storage at −20°C. The results obtained from a preliminary PT program on five expert laboratories confirmed that a single tube QC sample prepared could be used as a PT item with various Hb and DNA analyses methods. Conclusion: A single lyophilized control sample has been generated for use in hemoglobinopathies' internal and external quality control program. Unlike other available control materials, which are used for individual testing, a single‐tube QC sample generated can be used to control the pre‐analytical and analytical processes of both Hb and DNA analyses and is suitable for use in the PT program of hemoglobinopathies. [ABSTRACT FROM AUTHOR]

Key Content: The haemoglobinopathies encompass a complex collection of red blood cell disorders that are responsible for considerable morbidity and mortality in women and their unborn children.Sickle cell disease and the thalassaemias are the commonest haemoglobinopathies encountered in UK clinical practice.A consistent standard of care will enable women with haemoglobinopathies to have a pregnancy that is as safe as possible, with good outcomes and minimal long‐term effects on their health and the health of their babies.The most effective way to deliver a consistent standard of care for these women is via the multidisciplinary team (MDT). The MDT should include a haematologist, cardiologist, maternal medicine obstetrician, specialist midwife, reproductive medicine specialist and a nurse specialist.The care of these women, within the MDT, should start with pre‐conception advice and continue through their antenatal care, intrapartum support and finally, provide postnatal considerations including contraception advice. Learning Objectives: To understand the inheritance, incidence, detection and pathophysiology of the commonest haemoglobinopathies.To appreciate the role of pre‐conception advice and prenatal diagnosis in the management of women with a haemoglobinopathy.To appreciate the multidisciplinary team approach in managing women with these conditions. Ethical Issues: Prenatal diagnostic techniques can be used to diagnose an affected pregnancy; however, diagnosis after conception means families must address the option of terminating the pregnancy. This requires expert counselling to minimise long‐term sequelae.The definitive prenatal tests – chorionic villus sampling and amniocentesis – are both associated with a small risk of miscarriage.Non‐invasive free fetal DNA (ffDNA) tests that will minimise the risk of testing to the developing fetus are being developed, but use of these tests will still require expert counselling both before and after a test is taken. [ABSTRACT FROM AUTHOR]

Background: High performance liquid chromatography (HPLC) is the most commonly used method for detection and quantitative estimation of hemoglobin variants. Hemoglobinopathies are amongst the most common genetically inherited disorders, however, the exact magnitude of different hemoglobinopathies is obscure in India. This study was done with the aim of analyzing the different findings in HPLC using D-10 analyzer and evaluating the spectrum of different hemoglobin disorders in a hospital-based population of South Delhi. Such a prevalence study would be useful to review the various strategies that can be implemented for effective control and prevention of these disorders. Methods: A hospital based descriptive observational study was conducted in which all OPD and IPD patients who were advised HPLC during their clinical workup were included. Analysis of EDTA blood samples was done by Bio Rad D10 Dual program HPLC instrument. The exact percentage of HbA, HbA2, HbF and any other variant hemoglobin was estimated. Presumptive identification of hemoglobin variants was made primarily by their percentage, retention time (RT) and peak characteristics. HPLC findings were correlated with the clinical history, family history and the CBC and peripheral smear findings in all cases. Results: On HPLC analysis, 79% of the patients had no abnormality detected and the report was within normal limits. The commonest hemoglobinopathy was Beta Thalassemia Trait followed by HbE trait. The other hemoglobinopathies detected were HbD Punjab Heterozygous (3 cases, 0.5%), Beta thalassemia homozygous (3 cases, 0.5%), Sickle cell Heterozygous (2 cases, 0.3%), HbJ Meerut Heterozygous (2 cases, 0.3%). One case each of Sickle cell Homozygous (0.15%), Compound Heterozygous HbS/beta thalassemia trait (0.15%), HbE Homozygous (0.15%), Compound Heterozygous HbE/beta thalassemia trait (0.15%), and Homozygous delta beta thalassemia (0.15%) were also diagnosed. Conclusion: This study gives an important insight to the present day scenario of hemoglobinopathies in patients in South Delhi in relation to the hematological profile. It highlights the chromatogram findings of different hemoglobinopathies on the D10 analyzer. The comprehensive data obtained by such series can help in the formulation and development of infrastructure and policies for hemoglobinopathy prevention, diagnosis and management. [ABSTRACT FROM AUTHOR]

Objectives: HBB-related significant hemoglobinopathies have been anecdotally associated with low fetal fraction on noninvasive prenatal screening (NIPS). We sought to compare the difference in fetal fraction using NIPS in women with HBB-related significant hemoglobinopathies (HSH) and women with normal hemoglobin.Study Design: This is a retrospective case-control study. Cases were women with a diagnosis of HSH using NIPS from a commercial laboratory. The comparison group was women with hemoglobin AA from a tertiary care center database. We tested for differences in median fetal fraction using quantile regression analysis, adjusting for maternal body weight and gestational age.Results: This study includes 35 women with clinically significant HSH and a comparison group of 636 women with hemoglobin AA. Adjusting for gestational age and body weight, the median fetal fraction was 4.1 point lower in the HSH than in the comparison group (β - 4.1; 95% -5.7 to -2.5, p < .05). The rate of no-calls due to low fetal fraction was significantly higher in the clinically significant HSH group than in the comparison group [HSH: n = 9/35, 25.7% versus comparison: n = 32/636, 5.0% (p < .001)].Conclusion: Women with HSH were more likely to have a lower fetal fraction and ultimately a five-fold higher no-call rate. What's already known about this topic?Low fetal fraction is one of the most common causes of no-call result in noninvasive prenatal screeningHigh maternal weight, early gestational age and fetal aneuploidies are associated with low fetal fraction What does this study add?HBB-related significant hemoglobinopathies are associated with low fetal fractionReduction in fetal fraction due to HBB-related significant hemoglobinopathies may also result in higher no-call rate. [ABSTRACT FROM AUTHOR]

The article focuses on the impact of Voxelotor, an oral sickle hemoglobin inhibitor, on the quantitation of HbS levels in a patient with sickle cell disease. Topics include the patient's clinical presentation, the challenges in accurately quantifying HbS levels using high-performance liquid chromatography (HPLC) due to Voxelotor treatment, and the importance of providing information about the patient's drug treatment to ensure proper laboratory test interpretation.

A female patient aged 47 years presented with a hemoglobin A1c (HbA1c) level of 54.6%, as measured by ion-exchange high-performance liquid chromatography (HPLC), and a glucose level of 106 mg/dL. The HbA1c was re-evaluated using a turbidimetric inhibition immunoassay and found below the level of detection. Hemoglobinopathy testing led to the identification of a hemoglobin variant consistent with Hb Raleigh, in which a valine → alanine substitution on the beta chain effects a charge difference, resulting in coelution with HbA1c on HPLC and a spuriously high reading. Many Hb variants may interfere with HbA1c measurement and generate misleading results. The unique properties of Hb Raleigh may give rise to analytical errors when evaluating HbA1c using 2 different methods—molecular charge–based (eg, HPLC) and molecular structure–based (eg, immunoassay)—yielding diametrically opposed results. Consequently, recognition and diagnosis of this entity are essential in patients with Hb Raleigh, especially when monitoring long-term glucose control. [ABSTRACT FROM AUTHOR]

Introduction: Hemoglobin (Hb) analysis is a key testing for diagnosis of hemoglobinopathies. Accurate analysis, interpretation of results, and genetic risk assessment are important. We report on 8 years of the proficiency testing (PT) program for hemoglobinopathies in Thailand. Methods: Laboratory participants were required to test two simulated PT items in each cycle using capillary electrophoresis, one was a husband and another was his pregnant wife. Related hematological parameters were provided. The participants also provide interpretation and evaluate the risk of having three severe thalassemia diseases in an expected fetus. Three cycles were operated per year in accordance with the ISO17043 and ISO13528 guidelines. A total of 84 laboratories throughout Thailand were participated. Results: A total of 24 PT cycles were performed during 2012‐2019. Most participants had Excellent performance for the PT items with normal, β‐thalassemia trait, hemoglobin E trait, hemoglobin E trait with α‐thalassemia, and Hb H disease. However, when the PT items with homozygous Hb E and Hb E‐β‐thalassemia were tested, an increase in a Needs improvement performance was noted. From 24 PT cycles, the performance with Excellent, Good, Fair, and Needs improvement was ranging from 10.5%‐95.8%, 0%‐11.3%, 0%‐77.2%, and 2.3%‐37.0%, respectively. Conclusion: Most participants have proven their performance to be reliable and demonstrated their abilities to provide interpretation and genetic risk assessment on most of the PT items. For complex thalassemia however, a need to improve the interpretation and risk assessment skills is required which is essential for effective prevention and control of severe thalassemia diseases in Thailand. [ABSTRACT FROM AUTHOR]

Background: Antenatal screening is vital to identifying couples at risk of having children with a clinically significant haemoglobinopathy. In Australia, immigration is increasing carrier incidence. Methods: A retrospective analysis was performed of full blood count, high-performance liquid chromatography and haemoglobin electrophoresis of women and their partners who underwent antenatal haemoglobinopathy screening over three years at a major NSW laboratory. Genetic testing results were included where available. Results: One thousand six hundred and twenty-eight women and 729 male partners were screened at a median gestation of 14 weeks. 8.2% of women had a clinically significant result, with a median 16-day interval to partner testing. In 35% of couples screened simultaneously, the partner did not require testing. Genetic confirmatory testing was performed in 65% of high risk couples. Conclusion: There was a significant delay to antenatal haemoglobinopathy screening for mothers, limiting time for genetic diagnosis, prenatal diagnosis and management of affected pregnancies. Screening should be performed earlier. Simultaneous couple testing is not cost-effective. [ABSTRACT FROM AUTHOR]

Aim: To know the patterns of hemoglobinopathies and their prevalence in Kerbala society by using high performance liquid chromatography and to conclude if there is any correlations between different hematological parameters in Hemoglobinopathy patients. A total of 70 cases studied from 16th of February 2018 to 20th of June 2018 for hemoglobin variant analysis at the teaching labrotarioes of Al- Hussseini Teaching hospital which were studied for patterns of hemoglobinopathies. When the samples were received, Complete Blood Counts including: Hemoglobin concentration, Total White blood cells count (WBC), Mean Cell Volume (MCV), Mean Cell Haemoglobin (MCH), Mean Cell Hemoglobin Concentration (MCHC), Serum ferritin, Total Iron Binding Capacity ( TIBC), Hemoglobin H (HbH) preparation were done. Out of total 70 patients screened for patterns of hemoglobinopathies the result of the study revealed that 48 Patients which represent(68.57 %) of total patients had B-thalassemia trait which form the predominant percentage of patients with haemoglobinopathy, 11.85% of patients had sickle cell trait, 5.71% of them had B-Thalassemia Major, 4.29% had Hb S/B+Thalassemia Trait, 2.86% had HbS/Alpha thalassemia trait, 1.43% of them had Hb S homozygosity, 1.43% Alpha thalassemia trait, 1.43% had D-Los Anglos, 1.43% had HbS/B+ Thalassemia trait and 1.43% had HbC/B-Thalassemia trait. [ABSTRACT FROM AUTHOR]

Hemolytic anemias are a group of disorders with varied clinical and molecular heterogeneity. They are characterized by decreased levels of circulating erythrocytes in blood. The pathognomic finding is a reduced red cell life span with severe anemia or, compensated hemolysis accompanied by reticulocytosis. The diagnostic workup or laboratory approach for hemolytic anemias is based on methodical step-wise testing which includes red blood cell morphology, hematological indices with increased reticulocyte count along with clinical features of hemolytic anemias. If conventional laboratory tests are unable to detect the underlying cause of hemolysis, genetic testing is recommended. Sanger sequencing along with conventional testing is the most efficient way to diagnose the underlying genetic causes, especially in thalassemias/hemoglobinopathies, if required. However, hemolytic anemias being highly heterogeneous disorders, next-generation sequencing-based screening is rapidly becoming an efficient way to decipher the etiologies where common causes have been excluded. [ABSTRACT FROM AUTHOR]

The article present case study of a 20-month-old male with complaints of 1 day of fever in the setting of 2 weeks of upper respiratory symptoms. Further discusses finding of hypoxemia, severe anemia and hemolysis; and Hemoglobin electrophoresis performed by Mayo Clinic later confirmed Hemoglobin M-Hyde Park.

Consanguinity is a social behavior characterized by the arrangement of marriages between relatives. It coincides generally with the geographic distribution of recessive genetic diseases as it increases the likelihood of homozygosis and, consequently, the incidence of their pathologies in the population. In this pilot study, we assess the effect of inbreeding on the burden of hemoglobinopathies in Northern Morocco. From January 2016 to December 2018, 197 children born in the studied region to three ancestral generations and diagnosed with hemoglobinopathies were subject to investigation. The rate of consanguinity in the parents' generation of children with hemoglobinopathies was 50.25%, with first cousin marriages accounting for 68.69% of consanguineous unions (FI = 0.02). The corresponding rates in the general population, based on a sample of N = 900, were 29.67% and 82.02%, respectively. The marriages between first cousins are the most common among the other types of consanguineous unions. Our study propounds that consanguinity substantially contributes to the hemoglobinopathy burden in the studied region and has changed little over time. Refraining from consanguineous marriages and detecting couples at risk could contribute to the reduction of the incidence of genetic diseases in our country. [ABSTRACT FROM AUTHOR]

The article presents a case study of a female infant with splenic rupture with multiple etiologies. It notes the complete blood count (CBC) and echocardiogram for atrial septal defect, transferred to the neonatal intensive care unit and low hemoglobin, with the examination of a had ultrasound and abdominal ultrasound.

Introduction: The hemoglobinopathies pose a significant health burden in India. Apart from the β thalassemias and sickle cell disorders, α thalassemias and structural hemoglobin variants are also common. Here we have reviewed the phenotypic and molecular diversity of hemoglobinopathies encountered at a referral center in western India over a period of 15 years. Materials and Methods: Screening for hemoglobinopathies was done using HPLC and cellulose acetate electrophoresis. Molecular characterization was done using Covalent Reverse Dot Blot Hybridization (CRDB), Amplification Refractory Mutation System (ARMS), GAP PCR and direct DNA sequencing. Results: The study includes 31 075 individuals who were referred for diagnosis of hemoglobinopathies and prenatal diagnosis. Of these 14 423 individuals showed various hemoglobin abnormalities. Beta genotyping in 5615 individuals showed the presence of 49 β thalassemia mutations. 143 β thalassemia heterozygotes had normal or borderline HbA2 levels. We identified three δ gene mutations (HbA2 Pellendri, HbA2 St.George, HbA2 Saurashtra) in β thalassemia heterozygotes leading to normal HbA2 levels. The commonest defects among the raised Hb F determinants were Gγ(Αγδβ)0 Indian inversion and the HPFH‐3 Indian deletion. A total of 312 individuals showed the presence of α thalassemia, of which 12.0% had a single α gene deletion (−α/αα). HbH disease was identified in 29 cases with 10 different genotypes. Alpha globin gene triplication was seen in 2.1% of β thalassemia heterozygotes with a thalassemia intermedia phenotype. Seven unusual α chain variants and eight uncommon β chain variants were identified. Conclusion: The repertoire of molecular defects seen in the different globin genes will be valuable for management and control of these disorders both in India as well as in other countries where there is a huge influx of migrant populations from India. [ABSTRACT FROM AUTHOR]

Abstract: The hemoglobinopathies, as a group, are one of the most common serious monogenic diseases in the world. An accepted and widely adopted approach to reduce the number of new cases involves carrier‐screening programs, with the option of prenatal diagnosis (PND) or preimplantation diagnosis (preimplantation genetic testing for monogenic disease, PGT‐M) for carrier couples. The aim of PND is to provide an accurate result as early in pregnancy as possible, which necessitates prior identification of the parental disease‐causing mutations, as well as safe and timely biopsy of fetal material. PGT‐M aims to characterize the genetic status of in vitro fertilized embryos during assisted reproductive technology (ART), in a few cells biopsied from oocytes/zygotes or embryos, in order to initiate an unaffected pregnancy. Another application of PGT‐M is preimplantation genetic diagnosis for human leukocyte antigen (PGD‐HLA), which, in addition to identifying unaffected embryos, also characterizes the embryos that are HLA compatible with an existing affected child requiring a hemopoietic stem cell transplantation (HSCT). This review outlines the current practices related to these procedures, with emphasis on the aspects related to laboratory techniques. Finally, future prospects related to developments in noninvasive prenatal diagnosis are discussed. [ABSTRACT FROM AUTHOR]

The article presents a case study that involves an asymptomatic neonate with reduced peripheral oxygen saturations (SpO2), whereby the patient's father has a confirmed rare haemoglobinopathy, haemoglobin Titusville. It reports that Haemoglobin Titusville is a low-oxygen affinity haemoglobinopathy involving a single nucleotide change from G to A at codon 94 of the alpha globin gene.

Hemoglobin [Hb] J-Singapore [a79(EF8)Ala→Gly, GCG>GGG] is a very rare α-globin chain variant. In the present study, the authors reported, for the first time, the Hb J-Singapore in a 31-year-old Thai pregnant woman. She was seen by an obstetrician at her fifteenth week of gestation. Based on routine antenatal thalassemia and hemoglobinopathy screening, her Hb analysis was performed by high performance liquid chromatography [HPLC] and the abnormal Hb peak with a value of 23.6% was observed at the retention time of 1.83 minutes. The abnormal Hb peak was also found at zone 12 of capillary electrophoresis [CE] electrophoregram, which was similar to the peak of Hb Bart's and Hb J-Buda. The direct DNA sequencing revealed the GCG>GGG mutation at codon 79 of α2-globin gene as previously described for Hb J-Singapore. In addition, the developed multiplex allele specific polymerase chain reaction [MAS-PCR] showed the 63 2 bp amplified fragment from Hb J-Singapore allele. Thus, the knowledge and understanding of this hemoglobinopathy will be used to assist in diagnosis, management, and counseling for needed patients. [ABSTRACT FROM AUTHOR]

The current influx of economic migrants and asylum seekers from countries with a high prevalence of haemoglobinopathies creates new challenges for health care systems and diagnostic laboratories. The migration of carriers introduces new and novel haemoglobinopathy mutations to the diagnostic repertoire of a laboratory, often creating new pressures to improve and update the carrier screening technology and diagnostic scope. For antenatal screening programmes, the marriage of partners from different ethnic groups can lead to the risk of compound heterozygote children being born novel mutation combinations, creating problems in the provision of accurate advice regarding the expected phenotype of the thalassaemia or haemoglobinopathy disorder. In the UK, the impact of immigration required the National Haemoglobinopathy Reference laboratory to change the strategy and techniques used for the molecular diagnosis of thalassaemia and the haemoglobinopathies. In 2005, due to the increasingly large range of β-thalassaemia mutations that needed to be diagnosed, the laboratory switched from a three-step screening procedure using ARMS-PCR to a simpler but more expensive one-step strategy of DNA sequencing of the beta and alpha globin genes for all referrals. After ten years of employing this strategy, a further 57 novel thalassaemia and haemoglobionpopthy alleles were discovered (11 new β-chain variants, 15 α-chain variants, 19 β-thalassaemia mutations and 12 α+-thalassaemia mutations), increasing further the extremely heterogeneous spectrum of globin gene mutations in the UK population. [ABSTRACT FROM AUTHOR]

The article presents a case of 7-month-old white female infant with parental concerns of constipation. The infant was placed on supplemental oxygen by nasal cannula with no improvement. She presented mild anemia and trace carboxyhemoglobin in blood. Bubble-contrast echocardiogram suggested a right-to-left shunt or a patent formane ovale. Chest computed tomography and abdominal ultrasound were normal.

Introduction Differentiation of homozygous hemoglobin (Hb) E with and without α0-thalassemia is subtle on routine hematological ground. We examined in a large cohort of homozygous Hb E if the level of Hb A2 is helpful. Methods A total of 592 subjects with homozygous Hb E were recruited from ongoing thalassemia screening program. Additionally, five couples at risk of having fetuses with Hb Bart's hydrops fetalis who were homozygous Hb E were also investigated. Hb analysis was performed using capillary electrophoresis system. Globin genotypes were defined by DNA analysis. Results Subjects were classified into four groups including pure homozygous Hb E (n=532), homozygous Hb E/α0-thalassemia (n=48), Hb Constant Spring EE Bart's disease (n=8), and Hb EE Bart's disease (n=4). The levels of Hb A2 were found, respectively, to be 4.97±0.69, 6.64±1.02, 4.86±0.87, and 7.60±1.04%. Among five couples at risk, α0-thalassemia was identified in three subjects with Hb A2>6.0%. Conclusions Increased Hb A2 level is a useful marker for differentiation of homozygous Hb E with and without α0-thalassemia. This should lead to a significant reduction in number of referral cases of homozygous Hb E for molecular testing of α0-thalassemia in routine practice. [ABSTRACT FROM AUTHOR]

We report two very rare changes in the second intron of theHBBgene, a substitution at nucleotide (nt) 726 [IVS-II-726 (A>G) (β+), NM_000518,HBB: c.316-125A>G] and a deletion of a cytosine at nt 809 [IVS-II-809 (–C) (β), NM_000518,HBB: c.316-42delC] identified during the screening program for hemoglobinopathies in the resident Sicilian population. The purpose of this study was to evaluate the clinical implication of these rare changes, particularly in coinheritance with known mutations in the globin clusters, in order to conduct an appropriate genetic counseling for at-risk couples. Molecular analysis detected the first rare nt substitution in two cases in simple heterozygosity and in two cases in association with other known mutations on globin genes, while the deletion was identified in a pregnant woman, carrier of β-thal, and in her fetus at prenatal diagnosis (PND) for hemoglobinopathies. The present study emphasizes the importance of sharing the observed changes in the globin gene cluster, especially in the case of new or rare undefined mutations, in order to facilitate the determination of their phenotypic expression and possible interactions with known molecular defects. [ABSTRACT FROM AUTHOR]

Since 1993, following the National Thalassemia Major Prevention Program and an increase in immigration and interracial marriages, especially in southern Taiwan, the distribution of hemoglobinopathies may have changed. This study investigates the epidemiologic transition of hemoglobinopathies. We analyzed 1870 specimens collected between 2003 and 2012 in southern Taiwan, used gap-polymerase chain reaction and PCR-restriction fragment length polymorphism-based methods, and confirmed genotypes of hemoglobinopathies by DNA sequencing. We found a 91% reduction in the incidence of thalassemia major compared with samples from between 1986 and 1995. The most common genotypes of α-thalassemia and α Hb variants were the SEA type (69.4%) and Hb Quong Sze (1.54%). The most common genotypes of β-thalassemia and β Hb variants were IVS-II-654 (46.2%) and Hb E (2.2%), respectively. Compared with studies performed in different areas of and time intervals in Taiwan, a higher prevalence of -α3.7, Hb Quong Sze, and Hb E and a lower prevalence of the SEA type were found in this study. However, the SEA type remained the most common genotype observed. In addition, an increasing number of cases with an -α3.7 type carrier, Hb Quong Sze carrier, and Gγ(Aγδβ)° were identified following a peak of interracial marriages between 2003 and 2005, reflecting a regional difference and the impact of interracial marriage. In conclusion, global migration and international marriage have changed the distribution of hemoglobinopathies in Taiwan. A more comprehensive prenatal screening for new immigrants with a longer follow-up is warranted. [ABSTRACT FROM AUTHOR]

Sickle cell disease (SCD) is the most prevalent hemoglobinopathy. Survival in patients with SCD has improved over the past few decades. These patients experience a lifetime of repeated acute pain crises, which are thought to result from sickling and microvascular occlusions; acute abdominal pain is common. Moreover, repeated crises often lead to organ dysfunction, such as asplenia, hepatic failure, and renal failure. The spleen, liver, biliary system, kidneys, and gastrointestinal tract can all be affected. Patients may undergo CT to further direct clinical management. We review the spectrum of CT imaging findings of abdominal manifestations in patients with SCD, from the acute microvascular occlusive pain crisis to the potential complications and chronic sequelae. [ABSTRACT FROM AUTHOR]

Hemoglobinopathies are caused by point mutation in globin gene that results in structural variant of hemoglobin. While 7 % of world populations are carrier of hemoglobinopathies, the prevalence of the disease varies between 3 to 17 % across different population groups in India. In a diagnostic laboratory, alkaline gel electrophoresis and cation exchange-based HPLC (CE-HPLC) are most widely used techniques for characterization of hemoglobin variants. In the above methods, the differential surface charge of hemoglobin molecule in variants is exploited for their characterization. Sometime, co-migration of variants in gel electrophoresis and co-elution or elution with unknown retention time in automated CE-HPLC might lead to ambiguity in the analysis of hemoglobinopathies. Under such circumstances, it is necessary to use other analytical methods that provide unambiguous results. Mass spectrometry-based proteomics approach and DNA sequence analysis are examples of such alternative methods. In the present study, liquid chromatography coupled to mass spectrometry has been used for three commonly observed variants in India, e.g., HbE, HbQ India and HbD Punjab that appeared with inappropriate results in the conventional analysis. A customized hemoglobin variant database has been used in the mass spectrometry-based analysis of those three variants. Mass spectrometry-based proteomics approach was used to analyze above variant sample accurately. [ABSTRACT FROM AUTHOR]

Hemoglobinopathies are one of the major problems in Pakistan. A retrospective analysis of blood samples of 2731 patients from 2010 to 2014 was done at National Institute of Blood Disease & Bone Marrow Transplantation for the workup of anemia or other blood-related disorders. Whole blood samples in EDTA were collected; complete blood counts with peripheral smears were prepared. Hemoglobin (Hb) electrophoresis on Genio was performed at alkaline pH. Samples showing borderline results were further tested by high-performance liquid chromatography or for specific mutation analysis by ARMS-PCR. Out of total 2731, 935 (34.2%) patients had hemoglobinopathies. Out of these 935 patients who had hemoglobinopathies, beta thalassemia minor 51.8%, beta thalassemia major 24.1%, HbD trait 6.7, sickle/ beta thalassemia 4.5%, sickle cell disease 3.9%, HbE trait 1.9%, and sickle cell trait 1.7% were most common hemoglobinopathies. Less prevalent were delta/beta thalassemia, HbE homozygous, HbD homozygous, and HbH disease. [ABSTRACT FROM AUTHOR]

Background HbA1c is used in the diagnosis and monitoring of diabetes mellitus (DM). Interference from hemoglobin variants is a well-described phenomenon, particularly with HPLC-based methods. While immunoassays may generate more reliable HbA1c results in the presence of some variants, these methods are susceptible to negative interference from high concentrations of HbF. We report a case where an accurate HbA1c result could not be obtained by any available method due to the presence of a compound hemoglobinopathy. Methods HbA1c was measured by HPLC, immunoassay, and capillary electrophoresis. Hemoglobinopathy investigation consisted of a CBC, hemoglobin fractionation by HPLC and electrophoresis, and molecular analysis. Results HbA1c analysis by HPLC and capillary electrophoresis gave no result. Analysis by immunoassay yielded HbA1c results of 5.9% (Siemens DCA 2000 +) and 5.1% (Roche Integra), which were inconsistent with other markers of glycemic control. Hemoglobinopathy investigation showed HbC with the hereditary persistence of fetal hemoglobin-2 Ghana deletion. Conclusion Reliable HbA1c results may be unobtainable in the presence of some hemoglobinopathies. HPLC and capillary electrophoresis alerted the laboratory to the presence of an unusual hemoglobinopathy. Immunoassays generated falsely low results without warning, which could lead to missed diagnoses and under treatment of patients with DM. [ABSTRACT FROM AUTHOR]

Background Real-life data on the use of R2 MRI for the assessment of liver iron concentration ( LIC) remain limited. Methods We conducted a cross-sectional analysis on 363 patients (mean age 35.6 yr, 44.1% men) with hemoglobinopathies (204 β-thalassemia major [ TM], 102 β-thalassemia intermedia [ TI], and 57 sickle cell disease [ SCD]) that were evaluated with R2 MRI as part of LICNET, an MRI network of 13 Italian treatment centers. Results The mean LIC was 7.8 mg/g (median: 4.0), with high LIC (>7 mg/g) noted in both transfused ( TM, TI 37%; SCD 38%) and non-transfused ( TI 20%) patients. Ferritin levels correlated with LIC in both transfused ( TM, TI, SCD) and non-transfused ( TI) patients ( P < 0.001), although lower values predicted high LIC in non-transfused patients (1900 vs. 650 ng/mL in TM vs. non-transfused TI). A correlation between LIC and ALT levels was only noted in HCV-negative patients (rs = 0.316, P < 0.001). The proportion of patients with high LIC was significantly different between iron chelators used ( P = 0.023), with the lowest proportion in deferasirox (30%) and highest in deferiprone (53%)-treated patients. Conclusions High LIC values persist in subgroups of patients with hemoglobinopathy, warranting closer monitoring and management optimization, even for non-transfused patients with relatively low ferritin levels. [ABSTRACT FROM AUTHOR]

Background: Short to intermediate integrated glycemic control is best determined by glycated albumin (GA). This assay is appropriate when interpretation of glycated hemoglobin (HbA1c) is critical because of hemoglobinopathies, severe anemias, or other factors that affect red blood lifespan as hemodialysis. We evaluated a new assay based on the enzymatic quantification of GA by ketoamine oxidase and an albumin-specific protease. Methods: Limits of blank, detection, and quantification; precision; linearity; accuracy; interferences; correlation with HbA1c; and serum vs plasma study have been evaluated on ILab® systems. Results: Limit of blank, detection, and quantification for GA (g/L) were, respectively, 0.26, 0.36, and 1.15. Repeatability and within-device precision CVs were lower than 2.11%, 1.61%, and 1.56% for GA (g/L), albumin (g/L), and GA%, respectively. Linearity for GA (g/L) and GA% was 1.2-36.8 and 5.5-92.2, respectively. Highest deviation from linearity was<11%and recovery was higher than 90%. Accuracy against the certified ReCCS Japan Clinical Chemistry Reference Material (JCCRM) 611 was <1%. Classical interfering substances had no significant impact. Correlation of GA% between ILab® Taurus and ADVIA system was y = 1.02[GA%]+0.25; R² = 0.994. No difference was found in the determination of GA% in serum vs plasma. Conclusions: GA enzymatic assay is a reliable, fully automated method allowing accurate and precise determination of GA in a routine laboratory. [ABSTRACT FROM AUTHOR]

Hb A1c measurement is subject to interference by hemoglobin traits and this is dependent on the method used for determination. In this paper we studied the difference between Hb A1c measured by HPLC in hemoglobin traits and normal chromatograms. We also studied the correlation of Hb A1c with age. Hemoglobin analysis was carried out by high performance liquid chromatography. Spearman’s rank correlation was used to study correlation between A1c levels and age. Mann-Whitney U test was used to study the difference in Hb A1c between patients with normal hemoglobin and hemoglobin traits. A total of 431 patients were studied. There was positive correlation with age in patients with normal chromatograms only. No correlation was seen in Hb E trait or beta thalassemia trait. No significant difference in Hb A1c of patients with normal chromatograms and patients with hemoglobin traits was seen. There is no interference by abnormal hemoglobin in the detection of A1c by high performance liquid chromatography. This method cannot be used for detection of A1c in compound heterozygous and homozygous disorders. [ABSTRACT FROM AUTHOR]

The thalassemias are among the most common monogenic diseases worldwide, a national health burden in India. There are estimated 7500–12,000 babies born with β-thalassemia major (β-TM) every year in this country. Couples who are at-risk of having children with hemoglobin (Hb) disorders desired to have the option of avoiding the birth of an affected child by prenatal diagnosis (PND). Thus, the prenatal women are a highly important target group for carrier screening and preventing the birth of thalassemic children in the country. The present study was conducted among 20,883 pregnant women, irrespective of gravida and duration of pregnancy, from the prenatal clinic of Nilratan Sarkar (NRS) Medical College & Hospital, Kolkata, West Bengal, India, from February 2009 to November 2012. Thalassemia carrier status was assessed by high performance liquid chromatography (HPLC) along with red blood cell (RBC) indices. Husbands of all thalassemia carrier women were advised and persuaded to undergo screening for hemoglobinopathies. The couples were counseled to undergo PND if both of them were detected to be thalassemia carriers. The data were statistically analyzed to evaluate the efficacy of this procedure. [ABSTRACT FROM AUTHOR]

Background The World Health Organization and the American and Canadian Diabetes Associations approved HbA1c > 6.5% as diagnostic for type 2 diabetes mellitus (T2DM). Hb variants and/or their chemically modified species can interfere with HbA1c measurements. We recently described a patient with Hb Wayne trait who was misdiagnosed with T2DM based on falsely elevated HbA1c. Hb Wayne is a clinically silent variant that exists as two isoforms: Hb Wayne I (Asn 139) and Hb Wayne II (Asp 139). Methods Hemoglobinopathy investigation was performed by HPLC (Bio-Rad VARIANT-II), alkaline and acid electrophoresis (Sebia Hydrasis2), capillary zone electrophoresis (Sebia CAPILLARYS2™) and DNA sequencing. HbA1c was measured by five methods. Results Hb Wayne eluted as two small fractions with retention times of 1.0 and 1.46 min on the HPLC (Bio-Rad VARIANT-II). Alkaline gel and capillary electrophoresis showed two small bands migrating faster than HbA. Hb Wayne generated spuriously high results on the Bio-Rad VARIANT-II Turbo 2.0, no results on the Tosoh G8, and did not interfere with either the Sebia CAPILLARYS2™ or immunoassays from Roche (tinaquant) and Siemens (Bayer DCA2000 +). Based on the Hb Wayne HPLC profile of 3 patients, an algorithm was developed to facilitate its detection, which identified 9 additional patients with Hb Wayne trait. Conclusions We characterize Hb Wayne by chromatographic and electrophoretic techniques and show the effect of Hb Wayne on five common HbA1c methodologies. We developed a quality assurance tool to assist in detecting Hb Wayne trait during HbA1c analysis on the Bio-Rad VARIANT-II™ Turbo 2.0. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Laboratory Medicine / Laboratoriums Medizin is the property of De Gruyter and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Laboratory Medicine / Laboratoriums Medizin is the property of De Gruyter and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Although commonly assessed in the context of microcytosis or sickling syndrome screening, hemoglobin mutations may not be as readily considered as a cause of other symptoms. These include macrocytosis with or without anemia, chronic or episodic hemolysis, neonatal anemia, erythrocytosis, cyanosis/hypoxia and methemoglobinemia/sulfhemoglobinemia. Hemoglobin disorders commonly interfere with the reliability of Hb A1c measurement. Because the clinical presentation can be varied and the differential diagnosis broad, a systematic evaluation guided by signs and symptoms can be effective. A tertiary care reference laboratory is particularly challenged by the absence of pertinent clinical history and relevant laboratory findings, and appropriate use of resources in a data vacuum can be problematic. To address these issues, our laboratory has constructed testing panels with a tiered strategy utilizing screening assays that detect the most common causes and reflexing additional assays that assess less common etiologies. See Figure 1. Our testing algorithm panels include a rapid hemoglobin fraction monitoring test, a generic diagnostic hemoglobin electrophoresis profile, and more specific diagnostic evaluations for microcytic anemia, hereditary hemolytic anemia, methemoglobinemia and sufhemoglobinemia and erythrocytosis. Use of these testing strategies has facilitated the identification of rare and complex hemoglobin disorders from a wide variety of ethnic groups, including over 500 distinct named alpha, beta and gamma variants (of which 60+ were novel variants at the time of first detection), 99 beta thalassemia mutations and greater than 20 large deletional beta globin cluster deletion subtypes. [ABSTRACT FROM AUTHOR]

Background: Thalasemia and other hemoglobinopathies are found in all the states of India and their prevalence is quite variable. In Uttar Pradesh very few studies are found which explore the spectrum of hemoglobinopathies. There is no such study which identifies the geographic distribution of high-risk communities with frequencies of hemoglobinopathies. Aim: Present study was carried out to determine the prevalence of hemoglobinopathies in different regions and castes of Uttar-Pradesh (UP) state. Materials and Methods: This is a preliminary community based cross-sectional, hospital based study, conducted at King George's Medical University, Lucknow, Uttar-Pradesh. Subjects aged between 18 to 65 years were enrolled for sampling. The anticoagulated blood was used for performing CBC (complete blood count), and hemoglobin electrophoresis to measure hemoglobinopathies. Results: The present study revealed higher(28/194;19.5%,p<0.05) prevalence of hemoglobinopathies in Lucknow district as compared to other districts of Uttar-Pradesh and Brahmin caste having high frequency (33/112;29.5%) followed by Jaiswal (3/13;23.1%) and Arora (2/9;22.2%). Conclusion: The data regarding prevalence and distribution can be useful in prevention and management of various hemoglobinopathies which play a vital role in the hospital blood bank as well as in the formulation of transfusion policies. [ABSTRACT FROM AUTHOR]

Introduction Capillary zone electrophoresis (CZE) at alkaline pH is one of the techniques used for hemoglobinopathy screening. In this study, an evaluation of the performance of a lower throughput CZE instrument, the Sebia Minicap Flex Piercing system, for this purpose is reported for the first time. Methods The analytical performance of the Sebia Minicap Flex Piercing system was evaluated. Furthermore, a method comparison between the Sebia Minicap Flex Piercing and two HPLC methods, that is, the Bio-Rad Variant Classic™ and the Bio-Rad D-10™ systems was performed by measuring samples with and without clinically relevant hemoglobin disorders. Results The analytical performance was acceptable for the determination of HbA, HbA2, HbS, and HbF, with an imprecision ≤2.0%. Method comparison showed a linear correlation for HbA2, HbF, and HbS measurements. Clinical concordance was acceptable when comparing CZE and HPLC. Conclusions Lower throughput CZE using the Sebia Minicap Flex Piercing can be used for precise and accurate first line screening and follow-up of hemoglobinopathies. [ABSTRACT FROM AUTHOR]

Introduction: Phenotype studies still occupy a key position in the diagnosis of hemoglobin (Hb) disorders. Material and Methods: In addition to the conventional methods for diagnosis of Hb disorders which are mostly based on differences in charge of the Hb molecules, some progresses have been brought by studying other properties of the globin chains. Among those, difference in hydrophobicity that may be investigated by reversed-phase HPLC (RP-HPLC) discriminates between variants displaying identical charges. Results: In this study, we show how an update of this method allows to recognize an α-chain variant from a γ-chain variant, a problem frequently during neonatal screening. We illustrate that RP-HPLC may also unravel unclear phenotypes which are modified by the presence of an additional variant not detected by the conventional methods, and help to characterize rare mutants. Also we show that it allows a clear distinction between variants with identical electrophoretical charges as exemplified by Hb Lepore Boston-Washington and Lepore Baltimore. Conclusions: In view of our results, RP-HPLC is a technique that needs to be used as a second step in the general strategy for a correct characterization of Hb variants. [ABSTRACT FROM AUTHOR]

Hemoglobinopathies belong to the most common monogenic hereditary diseases worldwide. A particularly high prevalence is seen in the Mediterranean countries, in parts of Asia, the Middle East and West Africa. Nevertheless, due to migration hemoglobinopathies play an increasingly important role in Germany as well. Basic testing consists of blood count and hemoglobin differentiation. In addition, an iron deficiency should be excluded if necessary. Molecular genetic testing is used for the verification of hematologic findings and serves in the assessment of risk for a severe form of a hemoglobinopathy in offspring. In order to ensure efficient diagnostics, family history and previous findings of the patient should be communicated to the laboratory. This is especially crucial in the case of prenatal diagnostics. [ABSTRACT FROM AUTHOR]

The diagnosis of hemoglobin variants that are not any of the better-known forms of thalassemia, sickle cell, HbC, HbD, or HbE anomalies is often challenging and requires detailed knowledge of the difference in symptoms and analysis. Experience in laboratory medicine plays an important role as the range of variants is extensive and lack of expertise can result in a wrong diagnosis. Hemoglobin variants with low oxygen affinity may present cyanosis and low oxygen saturation levels, whereas variants with increased oxygen affinity show polyglobulia and concomitant complications. Differential diagnosis of methemoglobin variants requires careful assessment, which can be problematic especially in pediatric medicine. Other variants, due to their instability, can cause more or less distinct hemolysis or thalassemia syndromes depicting serious disease patterns. Clear distinction is not always possible as several symptoms are often present. Many variants are autosomal dominant inherited. [ABSTRACT FROM AUTHOR]