Causes of Abnormal Hemoglobin Electrophoresis / 中国实验血液学杂志

OBJECTIVE@#To investigate the possible causes of abnormal hemoglobin electrophoresis results.@*METHODS@#The hemoglobin electrophoresis results of 5 696 patients in the First Affiliated Hospital of Chengdu Medical College from September 2018 to July 2021 were collected, and the abnormal results and clinical significance were analyzed.@*RESULTS@#The results of 486 patients (accounting for 8.53%) were abnormal, of which 300 cases had increased HbA2, 135 cases had decreased HbA2, 44 cases had increased F alone, and 7 cases had abnormal hemoglobin bands. Among the 486 patients, 246 patients were thalassemia gene positive (the positive rate was 50.62%), including 29 cases of α thalassemia, 208 cases of β thalassemia and 9 cases of αβ thalassemia. Among the patients with elevated HbA2, 68.67% were detected β thalassemia, 3.00% αβ thalassemia, 9.33% were suspected to be caused by macrocytosis, 6.33% by thyroid dysfunction, and 12.67% by uncertainty of the method. Among the patients with reduced HbA2, 21.48% were detected α thalassemia, 60.00% iron deficiency anemia, 8.15% were suspected to be caused by thyroid dysfunction, and 10.37% by uncertainty of the method. Among the patients with elevated F alone, the results of thalassemia gene detection were negative, 40.91% of them were suspected to be caused by macrocytosis, 27.27% by hereditary persistence of fetal hemoglobin, 29.55% by special physiological condition of pregnant women, and 2.27% by hyperthyroidism. Abnormal hemoglobin bands were detected in 7 patients, including 4 cases of hemoglobin D, 2 cases of hemoglobin E, and 1 case of hemoglobin J.@*CONCLUSION@#Thalassemia, iron deficiency anemia, macrocytosis such as megaloblastic anemia and non-severe aplastic anemia, thyroid dysfunction, hereditary persistence of fetal hemoglobin, abnormal hemoglobin diseases, the uncertainty of the method are all important causes of abnormal hemoglobin electrophoresis results. In clinical work, the patient's indicators should be comprehensively analyzed to determine the possible cause.

Ácido úrico en las gestantes con diagnóstico de drepanocitosis y preeclampsia / Uric acid in pregnant women diagnosed with sickle cell disease and preeclampsia

RESUMEN Introducción: El ácido úrico es el producto final del ciclo de las purinas y es fundamental como marcador de enfermedad renal, la gota y la preeclampsia. Este biomarcador ejerce efectos potenciales en la placenta y el feto de la gestante con drepanocitosis. Objetivo: Describir los efectos potenciales que produce el ácido úrico en las gestantes con drepanocitosis. Métodos: Se revisó literatura en inglés y en español, a través del sitio web PubMed y el motor de búsqueda Google académico, en artículos publicados en los últimos cinco años. Se utilizaron como términos de búsqueda: preeclampsia, ácido úrico y riesgos en las embarazadas con drepanocitosis. Se analizaron los aspectos más relevantes del tema en la bibliografía revisada. Análisis y síntesis de la información: El incremento del ácido úrico añadido a la vasoclusión, la hipoxia y la necrosis tisular a nivel de la placenta son mecanismos invocados en el desarrollo de la preeclampsia y los índices de partos prematuros que presentan. Es de destacar que no tiene una trayectoria uniforme en todas las pacientes, sobre todo se observa una mejor evolución (con menor presencia de estas complicaciones) en aquellas pacientes que muestran genotipo, niveles de hemoglobina fetal y haplotipo de la hemoglobina S más favorable. Conclusiones: El ácido úrico constituye un biomarcador útil y de alarma en el diagnóstico de la preeclampsia, una de las peores complicaciones tanto para la vida materna como para su descendencia, al ser la gestante con drepanocitosis una paciente de muy alto riesgo de parto pretérmino, prematuridad, bajo peso al nacer, nacidos muertos e infarto placentario.

ABSTRACT Introduction: Uric acid is the end product of the purine cycle and is essential as a marker of kidney disease, gout and pre-eclampsia. This biomarker has potential effects on the placenta and fetus of a pregnant woman with sickle cell disease. Objective: To describe the potential effects of uric acid in pregnant women with sickle cell disease. Methods: Literature in English and Spanish was reviewed, through the PubMed website and the academic search engine Google, in articles published in the last five years. The search terms were: pre-eclampsia, uric acid and risks in pregnant women with sickle cell disease. The most relevant aspects of the subject were analyzed in the reviewed bibliography. Analysis and synthesis of information: The increase in uric acid added to vasoocclusion, hypoxia and tissue necrosis at the level of the placenta are mechanisms invoked in the development of pre-eclampsia and the rates of premature births they present. It is noteworthy that it does not have a uniform trajectory in all patients, especially a better evolution is observed, with less presence of these complications in those patients who show a more favorable genotype, fetal hemoglobin levels and hemoglobin S haplotype. Conclusions: Uric acid constitutes a useful and alarm biomarker in the diagnosis of pre-eclampsia, one of the worst complications both for maternal life and for her offspring, as the pregnant woman with sickle cell disease is a patient at a very high risk of preterm delivery. prematurity, low birth weight, stillbirths and placental infarction.

Anémie chez les donneurs de sang volontaires après vérification de l'hémoglobine pré-don au Centre de Transfusion Sanguine de Libreville / Anemia in voluntary blood donors after verification of pre-donation hemoglobin at the Libreville Blood Transfusion Center

Introduction : La nécessité de disposer de produits sanguins labiles (PSL) de qualité est un impératif de la transfusion sanguine. Le don de sang n'est pas sans risque pour le donneur. Ce qui soulève la question de la perte de fer par spoliation sanguine. Ce constat a conduit à la réalisation de cette étude dans le but de rechercher l'anémie chez le donneur de sang volontaire jugé apte après évaluation de l'hémoglobine pré-don et d'en déterminer la cause. Patients et méthodes : Il s'agissait d'une étude transversale prospective réalisée au Centre National de Transfusion Sanguine (CNTS) de Libreville. La population d'étude était constituée de donneurs de sang, nouveaux ou anciens, volontaires en bonne santé chez qui les examens suivant ont été réalisés pour le diagnostic de l'anémie et celui de la carence en fer tout en excluant d'autre étiologies: l'hémogramme, le dosage de la Protéine C Réactive (CRP), le fer sérique, la ferritine, l'hepcidine et le test de diagnostic du paludisme (TDR).Résultats : Sur l'ensemble des deux cent quinze volontaires inclus, trente - quatre (15,8%) présentaient une anémie parmi lesquels douze femmes et vingt- deux hommes d'un âge moyen de 32,8 ±8,0. Le nombre de dons effectués était corrélé à la survenue de l'anémie selon le genre et l'âge du donneur. Il en a été de même pour les valeurs de la ferritine, du fer sérique.Conclusion : Le nombre important d'anémie est lié à un seuil bas de l'hémoglobine pré-don. Le caractère microcytaire hypochrome de l'anémie laisse supposer une origine ferriprive.

Introduction: The need to have quality labile blood products (LBP) is an imperative of blood transfusion. Blood donation is not without risk for the donor. This raises the question of the loss of iron by blood spoliation. This finding led to the realization of this study with the aim of looking for anemia in voluntary blood donors deemed suitable after evaluation of the pre-donation hemoglobin and to determine the cause.Patients and methods: This was a prospective cross-sectional study carried out at the National Blood Transfusion Center (CNTS) in Libreville. The study population consisted of blood donors, new or old, healthy volunteers in whom the following examinations were carried out for the diagnosis of anemia and that of iron deficiency while excluding other etiologies: blood count, C-Reactive Protein (CRP), serum iron, ferritin, hepcidin and malaria diagnostic test (RDT). Results: Of the two hundred and fifteen volunteers included, thirty-four (15.8%) presented anemia, including twelve women and twenty-two men with an average age of 32.8 ±8.0. The number of donations made was correlated with the occurrence of anemia according to the sex and age of the donor. It was the same for the values of ferritin, serum iron. Conclusion: The large number of anemia is linked to a low threshold of pre-donation hemoglobin. The hypochromic microcytic character of the anemia suggests an iron deficiency origin.

Association of HMIP1 C-893A polymorphism and disease severity in patients with sickle cell anemia

Abstract Introduction: Sickle cell anemia (SCA) is a Mendelian disorder with a heterogeneous clinical course. The reasons for this phenotypic diversity are not entirely established, but it is known that high fetal hemoglobin levels lead to a milder course of the disease. Additionally, genetic variants in the intergenic region HBS1L-MYB promote high levels of fetal hemoglobin into adulthood. Objective: In the present study, we investigated the HMIP1 C-839A (rs9376092) polymorphism, located at the HBS1L-MYB intergenic region block 1, in SCA patients. Method: We analyzed 299 SCA patients followed in two reference centers in Brazil. The HMIP1 C-839A (rs9376092) genotypes were determined by allele specific polymerase chain reactions. Clinical and laboratory data were obtained from patient interviews and medical records. Results: The median fetal hemoglobin levels were higher in patients with the HMIP1 C-839A (rs9376092) AA genotype (CC = 6.4%, CA = 5.6% and AA = 8.6%), but this difference did not reach significance (p = 0.194). No association between HMIP1 C-839A (rs9376092) genotypes and other clinical and laboratorial features was detected (p > 0.05). Conclusion: In summary, our data could not support the previously related association between the HMIP1 C-893A (rs9376092) polymorphism and differential fetal hemoglobin levels.

Droga antimetabolítica en pacientes con enfermedad de células falciformes en el centro hematológico del hospital de capacitación de Kerbalaa / Antimetabolite drug in patients with sickle cell diseases in hematological center of Kerbalaa training hospital

Antecedentes: el fármaco antimetabolito aumenta el nivel de hemoglobina fetal y reduce la frecuencia de crisis en pacientes con anemia de células falciformes. Objetivo: Evaluar el efecto de los antimetabolitos (hidroxiurea) en casos con crisis falciforme frecuente de anemia de células falciformes y talasemia no dependiente de transfusiones en el hospital de formación de Karbala desde abril de 2016 hasta diciembre de 2020. Pacientes y métodos: de 81 pacientes realizados en este estudio de casos y controles, cuarenta recibieron hidroxiurea y los otros cuarenta y un pacientes no. Se realizaron monitoreos cada dos semanas en los primeros tres meses mediante el envío para análisis (Hb, WBC, recuento de plaquetas y urea en sangre y creatinina sérica) LA PRENSA MÉDICA ARGENTINA Antimetabolite drug in patients with sickle cell diseases in hematological center of kerbalaa training hospital 161 V.107/Nº 3 además de la evaluación de los efectos secundarios de los medicamentos. Los cuarenta y un pacientes restantes que rechazaron la terapia con medicamentos los consideramos un grupo de control. Resultado: el grupo de casos que recibió hidroxilurea tuvo crisis principalmente después de 12 semanas desde la última crisis, mientras que el grupo de control tuvo crisis principalmente cada 3 a 7 semanas con un valor P=0,0001. No hubo efectos secundarios en el 77,5% de los casos que recibieron hidroxiurea. El 22,5% restante de los casos tuvo efectos secundarios menores o inespecíficos. Conclusión: En pacientes con drepanocitosis que sufrieron episodios recurrentes de crisis, la terapia con Hidroxiurea disminuye significativamente la frecuencia de la crisis dolorosa, con un bajo nivel de efectos secundarios en comparación con el grupo control.

Background: the antimetabolite drug increase fetal hemoglobin level and reduce the frequency of crisis in sickle cell disease patients. Aim: To evaluate the effect of antimetabolites (hydroxyurea) in cases with frequent sickling crisis of sickle cell disease and non-transfusion dependent thalassemia in Karbala training hospital from APRIL 2016 till December 2020. Patient and methods: from eighty-one patients conducted in this case control study, forty were received hydroxyurea and the other forty-one patients were not. Monitoring every two weeks in the first three months by sending for investigations (Hb, WBC, platelet count and blood urea and serum creatinine) in addition to assessment of drug side effects. The remaining forty-one patients who refused drug therapy we consider them as a control group. Result: the case group who received hydroxylurea had crisis mostly after 12 weeks from last crisis, whereas the control group had crisis mostly each 3 to 7 weeks in P value 0.0001. There was no side effect in 77.5% of cases received hydroxyurea.The remaining 22.5% of cases had less or nonspecific side effects. Conclusion: In patient with sickle cell diseases who suffered from recurrent episodes of crisis, Hydroxyurea therapy significantly decreases the frequency of the painful crisis, with low level of side effects in comparison with control group

Differential Diagnosis of Three Commonest Deletion β-Thalassemia in Chinese / 中国实验血液学杂志

OBJECTIVE@#To analyze the hematological characteristics of Chinese @*METHODS@#Hemoglobin electrophoresis and blood routine test were used to analyze the hematological indexes of all peripheral blood samples，PCR-Flow fluorescent hybridization and Gap-PCR were used to detect the globin gene mutations and the data were analyzed statistically.@*RESULTS@#The 3 types of deletion β- Thalassemia patients were showed as hypochromic small cell anemia. The MCH and MCV values of Taiwan type β-thalassemia patients were the lowest. The results of hemoglobin electrophoresis showed that the increasing of HbF was found in all of the 3 types. Except for the decreasing of Hb A2 in Chinese @*CONCLUSION@#Through analyze the hematological characteristics, it can be provide that the guidance for the differential diagnosis and genetic consultation of the three commonest deletion β-thalassemia in Chinese.

Progress in Gene Therapy of Sickle Cell Disease Based on Hemoglobin F--Review / 中国实验血液学杂志

Sickle cell disease (SCD) is a single gene genetic disease, which seriously threatens the life span and quality of patients. On the basis of the pathogenesis of SCD and the alternative therapy based on fetal hemoglobin F (HbF), the research progress of transcription factors involved in the regulation of HbF gene expression, such as BCL11A, ZBTB7A, KLF-1, c-MYB and SOX6, as well as the application of CRISPR / Cas9, TALEN, zinc finger nuclease and other gene editing technologies in this field has been made, providing a solid theoretical basis for the exploration of new treatment schemes for β- like hemoglobin diseases, such as sickle cell disease and β- thalassemia.

Anti-interference hemoglobin analysis system by high performance liquid chromatography / 生物医学工程学杂志

High performance liquid chromatography (HPLC) is currently the mainstream technology for detecting hemoglobin. Glycated hemoglobin (HbA1c) is a gold indicator for diagnosing diabetes, however, the accuracy of HbA1c test is affected by thalassemia factor hemoglobin F (HbF)/hemoglobin A2 (HbA2) and variant hemoglobin during HPLC analysis. In this study, a new anti-interference hemoglobin analysis system of HPLC is proposed. In this system, the high-pressure three-gradient elution method was improved, and the particle size and sieve plate aperture in the high-pressure chromatography column and the structure of the double-plunger reciprocating series high-pressure pump were optimized. The system could diagnose both HbA1c and thalassemia factor HbF/HbA2 and variant hemoglobin, and the performance of the system was anti-interference and stable. It is expected to achieve industrialization. In this study, the HbA1c and thalassemia factor HbF/HbA2 detection performance was compared between this system and the world's first-line brand products such as Tosoh G8, Bio-Rad Ⅶ and D10 glycosylated hemoglobin analysis system. The results showed that the linear correlation between this system and the world-class system was good. The system is the first domestic hemoglobin analysis system by HPLC for screening of HbA1c and thalassemia factor HbF/HbA2 rapidly and accurately.

Reaserch Advances on Induction of Fetal Hemoglobin (HbF) by Drugs in the Treatment of β-Thalassemia--Review / 中国实验血液学杂志

β-thalassaemias are inherited hemoglobin disorders caused by defects in the β-globin gene. In recent years, researches have re-mentioned the therapeutic significance of drug-induced fetal hemoglobin (HbF), which can reduce the imbalance of α and β chains and improve the severity of anemia by increasing the expression of γ chain. Drug trials, such as hydroxyurea, thalidomide and desitabine have shown elevated hemoglobin, decreased blood transfusion dependence, and reduced symptoms other than anemia after treatment. In addition, in vitro experiments suggested that HbF can also induce by other drugs, which providing important clues for safe and effective HbF inducers. Therefore, this article reviews the current research progress so as to expect beneficial to clinical treatment.

Anemia neonatal grave secundaria a transfusion feto-materna: a proposito de un caso / Severe neonatal anemia due to fetomaternal hemorrhage: an ilustrative case

La transfusión feto-materna es el paso de eritrocitos fetales a la circulación materna. Cuando es masiva, tiene una incidencia aproximada del 0,2-0,9 %. Generalmente, se desconoce el agente desencadenante, pero, en ocasiones, se pueden identificar factores de riesgo. En el embarazo, suele ser asintomática; el síntoma más frecuente es la disminución de los movimientos fetales (el 26 %) en relación con la anemia grave. Se diagnostica mediante la detección de hemoglobina fetal en la sangre materna (test de Kleihauer o citometría de flujo). Se presenta a un recién nacido con anemia crónica secundaria a la transfusión fetomaterna, que, después del tratamiento con transfusión de concentrado de hematíes, tuvo como complicación síntomas de sobrecarga de volumen y empeoramiento clínico. Tras la realización de una exanguinotransfusión, evolucionó favorablemente, sin secuelas.

Fetomaternal transfusion (FMT) is defined by the transfer of fetal blood into the maternal circulation. The incidence of massive FMT is estimated to be approximately 0.2-0.9 % of births. Although a number of etiologies have been associated with FMT, most causes remain unidentified and the pregnancy is usually asymptomatic. The most frequent symptom is the decrease in fetal movements (26 %) in relation to severe anemia. Several diagnostic modalities for FMT are described (Kleihauer stain, flow cytometry). We describe a case of a newborn with chronic anemia secondary to FMT who, after treatment with transfusions of red blood cells, presented volume overload and clinical worsening as a complication. In this case, our patient needed exchange transfusion for definitive improvement without disability.

Understanding the Molecular Basis of Juvenile Myelomonocytic Leukemia and Its Application for Novel Drugs Development / 임상소아혈액종양

To date, hematopoietic stem cell transplantation (HSCT) is the only choice of therapy for most patients with juvenile myelomonocytic leukemia (JMML). Relapse remains a major problem. Approximately 90% of patients carry either somatic or germline mutations of genes participating in RAS signal transduction such as PTPN11, CBL, K-RAS, N-RAS, or NF1 in their leukemic cells, allowing an understanding of the molecular pathophysiology of JMLL and the development of novel drugs. As these genetic aberrations are mutually exclusive, the genetic change observed in JMML helps us to establish the diagnosis of JMML. Furthermore, the genetic abnormalities of JMML are an important prognostic factor, as the type of abnormality may determine disease progression. Recent studies have revealed a strong association between hypermethylation of some genes and already known poor prognostic factors such as older age, elevated fetal hemoglobin at diagnosis, and somatic mutation of PTPN11. These molecular characteristics may be the basis for a guideline to determine the treatment, especially when to proceed with HSCT. Recently, novel drugs have been used based on these molecular characteristics. 5-Azacitidine, an inhibitor of DNA methyltransferase and tipifarnib, a selective farnesyl transferase inhibitor, have been used to improve the outcome of JMML. In addition, drugs which inhibit the RAS signal transduction have been developed, which are less toxic and will improve outcome in the near future.

Analysis of clinical phenotype and genotype of unstable Hemoglobin Rush / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze the hematological and genetic characteristics of unstable hemoglobin Rush (Hb Rush) and compound heterozygote of Hb Rush and thalassemia.</p><p><b>METHODS</b>Peripheral blood samples and genomic DNA from three patients (including two ethnic Dai and one Han Chinese) with anemia of undetermined origin were collected. Hematological phenotypes of these patients were determined through red blood cell analysis and hemoglobin electrophoresis. Genotypes of alpha- and beta-globin genes, -158 XmnⅠ polymorphic site ofγ promoter region, and haplotypes of 7 polymorphic restriction sites in the beta-globin gene cluster were determined using PCR-based methods and DNA sequencing.</p><p><b>RESULTS</b>All patients have presented hypochromic microcytic anemia and hemoglobin fraction with significant increased measurement (30.5%-59.2%) in the region of fetal hemoglobin during alkaline medium electrophoresis. DNA analysis suggested that all patients have carried mutations leading to the unstable hemoglobin Rush (HBB codon 101, GAG>CAG, Glu>Gln). Two of them were compound heterozygotes of Hb Rush and thalassemia mutations of -α,CD17 and Hb E, respectively. Hb Rush mutation was associated with various haplotypes of the β-globin gene cluster. No significant association was found between increased abnormal hemoglobin fraction in the region of Hb F and the polymorphism ofγ promoter or large deletion of the beta-globin gene cluster.</p><p><b>CONCLUSION</b>This study has confirmed the distribution of Hb Rush among various Chinese populations and is the third report of its kind. Hb Rush can result in increased measurement of hemoglobin fraction in the region of fetal hemoglobin (Hb F) during routine hemoglobin electrophoresis under alkaline condition. Hb Rush heterozygote alone can lead to hypochromic microcytic anemia and thalassemia-like phenotype. Prenatal diagnosis of Hb Rush is necessary for carriers.</p>

Analysis of Cut-off Value in Screening of Thalassemia by Capillary Hemoglobin Electrophoresis for Pregnant Women from Shenzhen Region of China / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the cut-off value in screening of thalassemia in pregnant women from Shenzhen region by capillary hemoglobin electrophoresis.</p><p><b>METHODS</b>The data of capillary hemoglobin electrophoresis and genetic diagnosis of thalassemia from 2122 examined prenatal women were retrospectively analyzed. Capillary hemoglobin electrophoresis and α-, β- genetic diagnosis of thalassemia were carried out for every woman. Hemoglobin electrophoresis was performed using Capillarys 2 full-automated electrophoresis instrument. Gap polymerase chain reaction and reverse dot blot were used for genetic diagnosis of thalassemia genotyping test. The cut-off value in screening of thalassemia was determined by receiver operating characteristic curve and next to analyze the value of HbA2 and HbF in screening of thalassemia using the decided cut-off value.</p><p><b>RESULTS</b>The areas under the curve (AUC(Roc)) of HbA2 for diagnosis of α-, β- thalassemia were 0.75 and 0.981 respectively, and the AUC(Roc) of HbF for diagnosis of β-thalassemia was 0.787. When HbA2 ≤ 2.55 was taken as the cut-off value of HbA2 for diagnosis of α-thalassemia, the sensitivity, specificity, positive likelihood ratio (LR(+)) and negative likelihood ratio (LR(-)) were 89.5%, 54.8%, 1.98, 0.19 respectively. When HbA2 ≥3.9 was taken as the cut off value of HbA2 for diagnosis of β-thalassemia, the sensitivity, specificity, LR(+) and LR(-) were 96.1%, 99.8% 480.5, 0.04 respectively. When HbF ≥0.75 was taken as the cut off value of HbF for diagnosis of β-thalassemia, the sensitivity, specificity, LR(+) and LR(-) were 83.6%, 61.8% respectively.</p><p><b>CONCLUSION</b>The cut-off value in screening of thalassemia by capillarys 2 full automated electrophoresis instrument is different from that of the traditional method of hemoglobin electrophoresis, such as cellulose acetate membrane electrophoresis and agarose gel electrophoresis. Each laboratory should establish their own respective cut off value.</p>

γ-Globin Inductive Therapy of β-thalassemia and Its Relationship with MicroRNA / 中国实验血液学杂志

β-thalassemia is a chronic hemolytic anemia characterized by the reduction or absence of synthesis of β-globin chains because of the β-globin gene mutations. β-thalassemia belongs to the inherited hemoglobin disease, and occurs in some provinces of China, such as in Guangdong, Guangxi, Fujian, its prevalence is about 2%. The treatment of this disease include transfusion, iron chelating agent, hematopoietic stem cell transplantation, splenectomy, induced expression of Fetal Hemoglobin (HbF) and gene therapies. However, the mortality rate of this disease is still higher, thus some new treatments are urgently needed. In recent years, the study was mainly concentrated in 2 aspects: the normal β-globin gene transfer and endogenous γ-globin re-activation. Some studies showed that the expression of miRNAs was dysregulated in β-thalassemia. Some miRNAs could regulate γ-globin at posttranscriptional level, thus, the clarification of relationship between miRNAs and β-thalassemia is expected to provide experimental bases to β-thalassemia therapy. In this review, the induced therapy of γ-globin for β-thalassemia and its relationship with the miRNA are summarized.

Massive Fetomaternal Hemorrhage Diagnosed with High-performance Liquid Chromatography / 임상소아혈액종양

Massive fetomaternal hemorrhage (FMH) is a major cause of unexplained fetal death and neonatal anemia. FMH can be diagnosed using the Kleihauer-Betke test or flow cytometry by identifying the presence of fetal red cells in the maternal blood. However, timely diagnosis is a challenge because many hospitals lack the equipment needed to perform such tests. The authors experienced a case of FMH diagnosed via high-performance liquid chromatography (HPLC) which is generally used in measuring glycated hemoglobin (HbA1c) in a patient with unexplained neonatal anemia. A girl aged 2 days was transferred to our hospital for showing pallor and a hemoglobin level of 5.0 g/dL. HPLC revealed 3% fetal hemoglobin (HbF) in the maternal blood. HPLC is a quick test for quantifying HbF that is readily available in many hospitals and could serve as a promising alternative for diagnosing FMH.

Massive Fetomaternal Hemorrhage Diagnosed with High-performance Liquid Chromatography / 임상소아혈액종양

Massive fetomaternal hemorrhage (FMH) is a major cause of unexplained fetal death and neonatal anemia. FMH can be diagnosed using the Kleihauer-Betke test or flow cytometry by identifying the presence of fetal red cells in the maternal blood. However, timely diagnosis is a challenge because many hospitals lack the equipment needed to perform such tests. The authors experienced a case of FMH diagnosed via high-performance liquid chromatography (HPLC) which is generally used in measuring glycated hemoglobin (HbA1c) in a patient with unexplained neonatal anemia. A girl aged 2 days was transferred to our hospital for showing pallor and a hemoglobin level of 5.0 g/dL. HPLC revealed 3% fetal hemoglobin (HbF) in the maternal blood. HPLC is a quick test for quantifying HbF that is readily available in many hospitals and could serve as a promising alternative for diagnosing FMH.

Genetic variants associated with fetal hemoglobin levels show the diverse ethnic origin in Colombian patients with sickle cell anemia / Las variantes genéticas asociadas con niveles de hemoglobina fetal señalan diversos orígenes étnicos en pacientes colombianos con anemia falciforme.

Introduction: Fetal hemoglobin is an important factor in modulating the severity of sickle cell anemia. Its level in peripheral blood underlies strong genetic determination. Associated loci with increased levels of fetal hemoglobin display population-specific allele frequencies. Objective: We investigated the presence and effect of known common genetic variants promoting fetal hemoglobin persistence (rs11886868, rs9399137, rs4895441, and rs7482144) in 60 Colombian patients with sickle cell anemia. Materials and methods: Four single nucleotide polymorphisms (SNP) were genotyped by restriction fragment length polymorphisms (RFLP) and the use of the TaqMan procedure. Fetal hemoglobin (HbF) from these patients was quantified using the oxyhemoglobin alkaline denaturation technique. Genotype frequencies were compared with frequencies reported in global reference populations. Results: We detected genetic variants in the four SNPs, reported to be associated with higher HbF levels for all four SNPs in the Colombian patients. Genetic association between SNPs and HbF levels did not reach statistical significance. The frequency of these variants reflected the specific ethnic make-up of our patient population: A high prevalence of rs7482144-'A' reflects the West-African origin of the sickle cell mutation, while high frequencies of rs4895441-'G' and rs11886868-'C' point to a significant influence of an Amerindian ethnic background in the Colombian sickle cell disease population. Conclusion: These results showed that in the sickle cell disease population in Colombia there is not a unique genetic background, but two (African and Amerindian). This unique genetic situation will provide opportunities for a further study of these loci, such as fine-mapping and molecular-biological investigation. Colombian patients are expected to yield a distinctive insight into the effect of modifier loci in sickle cell disease.

Introducción. La hemoglobina fetal es un importante factor modulador de la gravedad de la anemia falciforme, cuya expresión está muy condicionada por el factor genético. Los loci asociados con el incremento de la hemoglobina fetal pueden presentar frecuencias alélicas específicas para cada población. Objetivo. Investigar la presencia y el efecto de las variantes genéticas rs11886868, rs9399137, rs4895441 y rs7482144 asociadas con la persistencia de hemoglobina fetal, en 60 pacientes colombianos con anemia falciforme. Materiales y métodos. Se hizo la genotipificación de los polimorfismos de nucleótido simple ( Single Nucleotide Polymorphisms, SNP) mediante la técnica de polimorfismos de longitud de fragmentos de restricción ( Restriction Fragment Length Polymorphisms, RFLP) y el procedimiento TaqMan. La hemoglobina fetal (HbF) se cuantificó utilizando la técnica de desnaturalización alcalina de la oxihemoglobina. Las frecuencias genotípicas se compararon con las reportadas en poblaciones de referencia global. Resultados. Se observaron variantes genéticas ya reportadas para aumento de HbF en los cuatro SNP. La asociación genética entre los SNP y el incremento de la HbF no alcanzó significancia estadística. La frecuencia de estos alelos reflejó la siguiente composición específica en esta muestra de pacientes colombianos: una gran prevalencia de rs7482144-'A', lo que indica que el origen de la mutación para la anemia falciforme es África occidental, y una gran frecuencia de rs4895441-'G' y rs11886868-'C', lo que denota la influencia significativa del origen genético amerindio. Conclusión. Los resultados evidenciaron que la población con anemia falciforme de Colombia no tiene un único origen genético, sino que existen dos (africano y amerindio). Esta situación genética única ofrece la oportunidad de llevar a cabo un estudio más amplio de estos loci a nivel molecular. Se espera que el estudio de pacientes colombianos permita una visión diferente del efecto de los loci modificadores en esta enfermedad.

Pattern of hemolysis parameters and association with fetal hemoglobin in sickle cell anemia patients in steady state

This study aimed to evaluate the influence of fetal hemoglobin (Hb F) on hemolysis biomarkers in sickle cell anemia patients. Methods: Fifty adult sickle cell anemia patients were included in the study. All patients were taking hydroxyurea for at least six months and were followed at the outpatient clinic of a hospital in Fortaleza, Ceará, Brazil. The control group consisted of 20 hemoglobin AA individuals. The reticulocyte count was performed by an automated methodology, lactate dehydrogenase and uric acid were measured by spectrophotometry and arginase I by enzyme-linked immunosorbent assay (ELISA). The presence of Hb S was detected by high-performance liquid chromatography. The level of significance was set for a p-value <0.05. Results: A significant increase was observed in the reticulocyte count and lactate dehydrogenase, uric acid and arginase I levels in sickle cell anemia patients compared to the control group (p-value <0.05). Patients having Hb F levels greater than 10% showed a significant decrease in the reticulocyte count, arginase I and lactate dehydrogenase. A significant decrease was observed in arginase I levels in patients taking hydroxyurea at a dose greater than 20 mg/kg/day. Conclusion: The results of this study show that sickle cell anemia patients have increases in the hemolysis biomarkers, lactate dehydrogenase, reticulocyte count, arginase I, uric acid and increases in Hb F can reduce the reticulocyte count and arginase I and lactate dehydrogenase levels.

Socioeconomic and demographic characteristics of sickle cell disease patients from a low-income region of northeastern Brazil

To characterize the socioeconomic and demographic aspects of sickle cell disease patients from the state of Rio Grande do Norte (RN), Northeast Brazil, and their adherence to the recommended treatment. Methods: This cross-sectional descriptive study was performed at referral centers for the treatment of hematological diseases. One hundred and fifty-five unrelated individuals with sickle cell disease who went to these centers for outpatient visits were analyzed. All the patients, or their caregivers, were informed about the research procedures and objectives, and answered a standardized questionnaire. Results: The patients were predominantly younger than 12 years old, self-declared as mulatto, lived in small towns fairly distant from the referral center, and had low education and socioeconomic levels. Individuals who were ten or younger were diagnosed at an earlier age. Almost 50% of the patients were taking hydroxyurea, 91.4% reported having received pneumococcal/meningococcal vaccinations and 76.1% received penicillin as antibiotic prophylaxis. However, the majority of them reported having difficulties following the recommendations of the physicians, mainly in respect to attaining the prescribed medications and transportation to the referral centers. Conclusion: These individuals have a vulnerable socioeconomic situation that can lead to an aggravation of their general health and thus deserve special attention from the medical and psychosocial perspectives. Thus, it is necessary to improve public policies that provide Brazilian sickle cell disease patients with better access to medical treatment, living conditions, and integration into society.

A Case of Long-term Survival with Autologous Recovery after Double Cord Blood Transplantation for Juvenile Myelomonocytic Leukemia / 임상소아혈액종양

A 1.1 year old boy was admitted to the Seoul National University Children's Hospital because of incidental findings of hepatosplenomegaly, skin lesion and multiple intra- abdominal lymphadenopathies. Anemia and thrombocytopenia were found based on the initial complete blood count (CBC) measurements. Because of bicytopenia and hepatosplenomegaly, bone marrow examination was performed which revealed hypercellular marrow with increased monocytes and granulopoiesis. The hemoglobin F level was high for his age, and monocyte production was increased. The patient was diagnosed with juvenile myelomonocytic leukemia at the age of 1.2 years. Chemotherapy with cytarabine, etoposide, vincristine, and isotretinoin was initiated. After 6 cycles of chemotherapy, the CBC normalized. He underwent double cord blood transplantation (dCBT), but chimerism studies showed autologous recovery. However, he did not show relapse during the 5 years post-transplant during which he received isotretinoin. He is surviving disease-free 9 years after dCBT.