Haptoglobin gene polymorphism and iron profile in sickle cell disease patients with inflammation in Yaounde, Cameroon.

BACKGROUND: Major sickle cell syndromes are the most common hemoglobinopathy in the world. The sickle cell patients are subjected to several factors causing inflammation, and the genetic identification of each individual allows to focus the possibility of allelic variations influence of a specific gene and then the polymorphism. This study aims at determining the distribution of HP gene (OMIM#140100) and their involvement on hematological parameters and the iron profile in the sickle cell patients presenting an inflammation condition during major sickle cell syndromes in Cameroun. METHODS: A case-control analytical study has been conducted over a period of 6 months. Cases consisting of sickle cell patients in a situation of inflammation and control of non-inflamed sickle cell patients. The patients presenting major sickle cell syndromes, interned and/or followed at the Hematology Department of the Regional Hospital of Bafoussam and the Central Hospital of Yaoundé have been recruited. HP genotyping was carried out at the Laboratory for Public Health Research Biotechnologies (LAPHER-Biotech) in Yaoundé using allele-specific PCR. Also, inflammatory, hematological parameters and martial assessment were explored by standard methods. Statistical analysis of the data was performed using the statistical tool R version 4.1.1. The comparison of proportions of alleles was made with the chi-square test, and the Wilcoxon test was used to compare the median between different groups using the statistical tool R version 4.1.1. RESULTS: We analyzed the samples of 149 patients. The HP polymorphism describes a significant frequency of the "1F" allele (69.8%) followed by the "2" allele (46.31%). In addition, 80 patients (53.69%), 48 (32.21%), and 21 (14.09%) presented the genotype HP 1-1, HP 2-1, and HP 2-2, respectively. And eighty-one percent (81%) patients with genotype HP 2-2 showed a significant higher relative frequency of thrombocytosis compared with the genotype HP 1-1 and HP 2-1, respectively (51.2% and 68.8%, p = 0.087). The proportion of inflammation in the HP 2-2 group was higher (57.1%) compared with the other groups (respectively 42.5% and 35.4% in the HP 1-1 and HP 2-1 groups). Furthermore, the median CRP was significantly higher in the HP 2-2 group compared with the other groups (p = 0.039). Moreover, the entire population of the HP 2-2 group showed an elevation of ferritin and IL6 unlike the HP 1-1 and HP 2-1 groups. CONCLUSION: This study demonstrates a higher frequency of genotype HP 1-1 followed by the HP 2-2 genotype in patients with major sickle cell syndromes. However, a larger proportion of patients with genotype HP 2-2 are associated with hematological profile disorders, inflammation, and dysregulation of iron metabolism. Then, the haptoglobin polymorphism contributes to the severity of major sickle cell syndromes.

Epidemiological and clinical characteristics of 66 Tunisian Sickle cell syndrome patients.

Introduction: Sickle cell syndrome (SCS) represent a real health problem. In this work, we propose to study the epidemiological and clinical features of 66 patients with SCS. Methods: This is a retrospective descriptive cross-sectional study carried out on a population of 66 patients with SCS, (36 S/S, 18 S/ß-thalassemia, seven S/C and five S/OArab), over a period of two years. Results: The average age of our population is 15.5 years ± 8.4. 36 patients (55%) were born to a consanguineous marriage and 35 (53%) had siblings with SCS. The average baseline hemoglobin in our patients is 9.1g/dL±1.51. S/C patients have significantly higher baseline hemoglobin than S/S, S/ß-thalassemia and S/OArab with p <0.05. Jaundice, mucosal skin pallor and hepatomegaly have been observed only in S/S, S/ß-thalassemia and S/OArab patients. The persistence of splenomegaly is more frequent in S/C than in S/S, and in S/-thalassemia than in S/S. The most common acute complications were vaso-occlusive attacks (69.7%) and worsening of anemia (54.54%). The most common chronic complication was cholelithiasis (36.36%). Conclusion: S/C patients present the best tolerated form and were the least affected by chronic complications and therefore can lead an almost normal life.

[Screening for nephropathy in major sickle cell syndromes in patients monitored at the National Reference Center for Sickle Cell Disease in Niamey, Niger]. / Dépistage de la néphropathie dans les syndromes drépanocytaires majeurs chez les patients suivis au Centre national de référence de la drépanocytose de Niamey, Niger.

BACKGROUND: Sickle cell anemia is the most common hereditary hemopathy in the world. It is a disease that attacks all the systems of the organism. The kidneys are among the most sensitive organs of this disease. The main objective of this study is to detect sickle cell nephropathy in patients followed at the National Reference Center for Sickle Cell Disease in Niamey. METHODS: It is a prospective study carried out over a period of one year (January to December 2016). It included patients aged at least two years who had not had a vaso-occlusive crisis (VOC) for 2 months and not transfused for at least 3 months. A questionnaire was sent to each patient to collect demographic, clinical and biological information. Each patient provided a fresh blood and urine sample to assess biological parameters. We used Schwartz's formula in children and CKD-EPI in adults to assess glomerular filtration rate. The Pearson correlation coefficient (r) was used to assess the relationship between the different parameters under study. The threshold for statistical significance was set at 0.05. RESULTS: Two hundred and eighty participants were included in the study. Adolescents (≤17years) were 226 (80.71%) and adults were 54 (19.29%). The mean age of the patients was 11.94±4.70years. It was lower in SS subjects and higher in SC. The SS form accounted for 87.5% of the three sickle cell disease phenotypes encountered. The age group 6-15years was the most predominant (42.86%). The mean baseline hemoglobin in the sample was 7.59±1.15g/dL ; (6.8 ±0.9d/dL) in SS patients and higher (10.5±2.1g/dL) in SC patients. The average glomerular filtration rate was 201.04mL/min/1.73m2. Glomerular hyperfiltration was found in 90% of the sample, it was lower (77.6%) in Sß thalassemia patients (P=0.000). In young subjects hyperfiltration was present in 84.95% against it was observed in only 29.63% of adults. Proteinuria was positive in 20% of patients. Positive proteinuria was found in 6.20% pediatric cases. The SC form was the most affected and in 74.6% of the patients it was positive at 1+. Chronic kidney disease (CKD) was found in 10% of the participants, of whom 75% were of the SS phenotype. Sß thalassemia subjects had no CKD. The male sex was predominant in subjects with CKD (P=0.000). Patients over 15 years of age accounted for more than 95% of patients in both forms of the disease (P=0.0001). CONCLUSION: The SS form of the disease, recurrent vaso-occlusive crisis, male sex and advanced age were the main precipitating factors in the development of renal function disorders.

[Major sickle cell syndromes and infections associated with this condition in children in Burkina Faso]. / Syndromes drépanocytaires majeurs et infections associées chez l 'enfant au Burkina Faso.

INTRODUCTION: This study aims to investigate infections in children with major sickle cell syndrome. METHODS: We conducted a monocentric descriptive retrospective hospital study in Ouagadougou, Burkina Faso, over a ten-year period. All children with major sickle cell syndrome (homozygous SS and double heterozygous SC, SDPunjab, Sß thalassemic, SOArab and SE) hospitalized for microbiologically confirmed infections were enrolled in the study. RESULTS: One hundred and thirty-three patients met our inclusion criteria. The SS phenotype accounted for 63.2% of cases and SC 36.8%. The frequency of infections was 21.8%. In 45.9% of cases, these affected children aged 0-5 years. The most frequent signs were osteoarticular pain (42.1%), cough (25.7%), abdominal pain (23.3%), pallor (43.6%). The major diagnoses were bronchopneumonia (31.6%), malaria (16.5%), osteomyelitis (12.8%) and septicemia (10.5%). The isolated pathogenic organisms were Streptococcus pneumoniae (35.5%) and Salmonella spp (33.3%). Third generation cephalosporins were the most commonly prescribed antibiotics. Gros mortality rate was 7.5%. CONCLUSION: Bacterial infections and malaria dominate the clinical picture of infections in children with major sickle cell syndrome at the at the Pediatrics University Hospital Center Charles De-Gaulle. This study highlights the importance of establishing a national program for the management of sickle-cell anemia, which could help prevent or reduce the occurrence of infections in children with sickle cell syndrome.

[Sickle cell syndrome. Association between hemoglobin S and ß thalassemia]. / Síndrome drepanocítico. Asociación de hemoglobina S y ß talasemia.

Sickle cell syndrome HbS/ß thalassemia is an inheritable mendelian type disease where two affected alleles are simultaneously present, one from HbS (ßS) and the other from ß thalassemia. That situation is mainly linked to individuals who share African and Mediterranean ancestors. The mutation responsible for HbS is a point mutation, whereas for ß thalassemia, there are more than 200 mutations that cause different degrees of deficiency synthesis of ß globin chain, which justifies the clinical and genetic heterogeneity of this syndrome. It is presented a clinical case of a young adult man with limited resources that consulted by longstanding bone pain. The patient presented anemia with a marked microcytosis. Hemoglobin electrophoresis was performed, an abnormal peak in position of HbS and high HbA2 fraction were detected. These last results indicated two possible molecular alterations simultaneously, for this reason the molecular study was performed looking for the most common ß thalassemia mutations in our population and, the point mutation responsible for S hemoglobinopathy. Clinical data and biochemical laboratory allowed the diagnosis of sickle cell syndrome. The molecular study confirmed the syndrome carrying mutations IVS-I nt 110 G > A, responsible for ß thalassemia and, codon 6 A > T (GAG → GTG: Glu → Val) responsible for S hemoglobinophaty. Since it is a disease of high health impact, it is important to provide genetic counseling to the whole family.

Síndrome drepanocítico: Asociación de hemoglobina S Y &ß talasemia / Sickle cell syndrome. Association between hemoglobin S and ß thalassemia

El síndrome drepanocítico HbS/β talasemia responde a la herencia de tipo mendeliana en simultáneo de un alelo βs de la hemoglobina S (HbS) y un alelo de β talasemia. Vinculado fundamentalmente a individuos que comparten ascendencia africana y de países del Mediterráneo. La mutación responsable de la HbS es puntual, mientras que para la β talasemia existen más de 200 mutaciones que causan diferentes grados de deficiencia de síntesis de la cadena de β globina, lo cual justifica la heterogeneidad clínica y genética de este síndrome. Se presenta el caso clínico de un adulto joven de escasos recursos que consulta por dolores óseos de larga data. Registra hemogramas con anemia y marcada microcitosis. Se le realizó electroforesis de Hb detectándose un pico anómalo en posición de HbS y elevada fracción de HbA2. El resultado de la electroforesis de hemoglobina indica dos posibles alteraciones moleculares en simultáneo, por tal motivo se realizó el estudio molecular de las mutaciones más frecuentes en nuestra población de β talasemia y de la mutación puntual responsable de la hemoglobinopatía S. A partir de la clínica y datos del laboratorio bioquímico se diagnosticó el síndrome drepanocítico y se confirmó por biología molecular la portación de las mutaciones IVS-Int 110 G > A (β talasemia) y del codón 6 A > T (GAG→GTG: Glu→Val) responsable de la hemoglobinopatía S. Dado que es una enfermedad de alto impacto sanitario, es importante un adecuado asesoramiento genético a toda la familia.

Sickle cell syndrome HbS/β thalassemia is an inheritable mendelian type disease where two affected alleles are simultaneously present, one from HbS (βS) and the other from β thalassemia. That situation is mainly linked to individuals who share African and Mediterranean ancestors. The mutation responsible for HbS is a point mutation, whereas for β thalassemia, there are more than 200 mutations that cause different degrees of deficiency synthesis of β globin chain, which justifies the clinical and genetic heterogeneity of this syndrome. It is presented a clinical case of a young adult man with limited resources that consulted by longstanding bone pain. The patient presented anemia with a marked microcytosis. Hemoglobin electrophoresis was performed, an abnormal peak in position of HbS and high HbA2 fraction were detected. These last results indicated two possible molecular alterations simultaneously, for this reason the molecular study was performed looking for the most common β thalassemia mutations in our population and, the point mutation responsible for S hemoglobinopathy. Clinical data and biochemical laboratory allowed the diagnosis of sickle cell syndrome. The molecular study confirmed the syndrome carrying mutations IVS-I nt 110 G > A, responsible for β thalassemia and, codon 6 A > T (GAG → GTG: Glu → Val) responsible for S hemoglobinophaty. Since it is a disease of high health impact, it is important to provide genetic counseling to the whole family.

Anemia de células falciformes: una revisión / Sickle Cell Anemia: A review

Resumen La anemia hemolítica más frecuente en la población mundial es la anemia de células falciformes (ACF), con una incidencia de 1/600 recién nacidos en Estados Unidos y en algunas regiones de España con incidencia de 1/5000 neonatos; en Colombia no hay registros respecto a la incidencia y prevalencia. La transmisión de la ACF es autosómica dominante. Los homocigotos (SS) no sintetizan Hb A y poseen eritrocitos con un 90 % de Hb S. El portador o heterocigoto (AS) tiene hematíes con Hb A mayor que 50 % y Hb S de 20 - 40 % y son usualmente asintomáticos. La Hb S se debe a una mutación en el gen de la cadena beta de globina, lo cual conlleva a la polimerización de la Hb en condiciones de baja oxigenación, lo cual origina un cambio en la morfología del eritrocito que adquiere la forma falciforme. La sintomatología es secundaria a la anemia hemolítica crónica, la vaso-oclusión en los diferentes órganos y la asplenia funcional, la cual predispone a la infección. Otras manifestaciones asociadas son el secuestro esplénico, la aplasia eritroide y las complicaciones órgano - especificas, que disminuyen la calidad de vida y predisponen a mayor mortalidad. Su manejo debe realizarse en centros de referencia donde haya un manejo integral, incluyendo el recurso humano y físico, ya que el manejo inadecuado y sus complicaciones disminuyen la sobrevida, la cual no es superior a los 45 años según reportes.

Abstract The most common hemolytic anemia in the world population is sickle cell anemia, with an incidence of 1/600 newborns in the United States and Spain some regions 1/5000 incidence of infants; in Colombia there are no records regarding the incidence and prevalence. ACF transmission is autosomal dominant. Homozygotes (SS) do not synthesize Hb A and possess erythrocytes with 90 % Hb S. The carrier or heterozygous (AS) is greater Hb RBCs with 50 % A and Hb S of 20 - 40 % and are usually asymptomatic. Hb S is due to a mutation in the gene for beta globin chain, leading to polymerization of Hb in low oxygenation, resulting in a change in morphology sickle erythrocyte acquiring form. The symptoms are secondary to chronic hemolytic anemia, vaso-occlusion in the different organs and functional asplenia which predisposes to infection. Other associated manifestations are splenic sequestration, erythroid aplasia complications and organ - specific, which decrease the quality of life and predispose to increased mortality. Its management must be performed in reference centers where there is a comprehensive management including human and physical resources, as improper handling and its complications decreased survival which is not more than 45 years according to reports.

Prevalence of variant hemoglobins and thalassemias in a maroon community in Sergipe, Brazil / Prevalência de hemoglobinas variantes e talassemia em uma comunidade quilombola em Sergipe, Brasil

Current analysis investigates the sickle-cell syndrome among members of a maroon community (comunidade quilombola) in the state of Sergipe, Brazil. The entire population, comprising five hundred and ninety-three people, was screened. Blood samples were collected from 318 people, aged between six months and fifty years, who underwent a solubility test to assess the presence of HbS, followed by Sickle-Cell Test to confirm its presence. Results revealed that 2.2% of the three hundred and eighteen people tested have hemoglobin HbS in their blood; 57% have type HbAS and 43% have a combination between thalassemia and heterozygous with a variable percentage of HbS ranging between 24.9 and 37.9%. Blood sampling revealed that only five out of the 318 people belonged to different families. Results are highly relevant for public health policies on the sickle-cell syndrome and its management.

Este trabalho investiga a síndrome da anemia falciforme entre os membros de uma comunidade quilombola no Estado de Sergipe, Brasil. Foi rastreada toda a população, que compreende 593 pessoas. Amostras de sangue foram coletadas de 318 pessoas, com idades entre seis meses e 50 anos, que foram submetidas a um teste de solubilidade para avaliar a presença de HbS, seguido pelo teste de falcização para confirmar a sua presença. Os resultados revelaram que 2,2% das 318 pessoas testadas apresentaram hemoglobina variante HbS em seu sangue; 57% possuíam a variante HbAS e 43% apresentaram uma combinação entre talassemia e heterozigotos com percentagens variáveis de HbS entre 24,9 e 37,9%. A coleta de sangue revelou que apenas cinco das 318 pessoas pertenciam a famílias distintas. Os resultados são altamente relevantes para o planejamento e gestão de políticas públicas de saúde sobre a síndrome falciforme

Alteraciones de la hemostasia en el síndrome drepanocítico / Hemostasis alterations in sickle cell syndrome

El síndrome drepanocítico (SD) comprende un grupo de anemias hemolíticas hereditarias de tipo multisistémico asociadas a la hemoglobina S. Los pacientes que padecen este síndrome tienen un mayor riesgo, en comparación con individuos sanos, de presentar accidentes cerebrovasculares, hipertensión pulmonar, necrosis avascular de articulaciones, síndrome torácico agudo y complicaciones durante el embarazo, asociados a un estado de hipercoagulabilidad inducido por alteraciones en los diferentes componentes de la hemostasia, que incluyen la activación del endotelio y de los sistemas plaquetario, de la coagulación y de la fibrinólisis. Esta revisión resume las alteraciones en la hemostasia reportadas en los pacientes con SD, en los cuales se ha demostrado: mayor interacción de células endoteliales con leucocitos, hematíes y plaquetas; aumento de la expresión de proteínas de adhesión, como el factor von Willebrand y sus multímeros de alto peso molecular; aumento de la adhesión y la agregación plaquetaria y de la expresión de proteínas en sus membranas. En el sistema de coagulación se ha detectado aumento en la expresión del factor tisular (FT) en micropartículas derivadas de diferentes células, aumento de marcadores de activación de este sistema, entre estos los fragmentos 1.2 de la protrombina y los complejos trombina-antitrombina y una disminución de las proteínas C y S que actúan como anti-coagulantes. Adicionalmente, se han encontrado aumentados los marcadores de activación del sistema fibrinolítico como los dímeros D y los complejos plasmina/antiplasmina. Todas estas manifestaciones favorecen la aparición de complicaciones trombóticas, implicadas en el deterioro de la calidad de vida de los pacientes. Se recomienda implementar en el diagnóstico y seguimiento de esta enfermedad, la determinación de variables del sistema hemostático, con el fin de identificar alteraciones en etapas tempranas y aplicar terapias que puedan prevenir complicaciones trombóticas.

Sickle cell syndrome (SCS) includes a group of congenital hemolytic anemias associated to the presence of hemoglobin S, which is characterized by acute pain episodes and progressive damage of different organs. Some patients with sickle cell syndrome have shown, when compared with healthy individuals, an increased risk of presenting stroke, pulmonary hypertension, avascular necrosis of joints, acute chest syndrome and pregnancy complications, associated to a hypercoagulable state induced by alterations in different components of hemostasis, such as changes that include activation of the endothelium, platelet activity, coagulation and fibrinolytic systems. This paper compiles hemostasis disorders, associated with thrombotic manifestations, reported until now in sickle cell syndrom. These patients have an increase in activation markers of the coagulation system, such as prothrombin fragment 1.2, thrombin-antithrombin complex, etc., depletion of natural anticoagulant proteins, abnormal activation of the fibrinolytic system and increased tissue factor expression. Similarly, abnormal expression of glycoproteins and increased adhesion and platelet aggregation have been reported. All these alterations produce a hypercoagulable state, which induces, among other things, the appearance of thrombotic complications. In view of the importance of controlling the different complications that can occur in patients with sickle cell syndrome, we recommend the implementation, in diagnosis and monitoring studies, of the evaluation of the different components of the hemostatic system, identifying alterations at an early stage and applying effective treatments to prevent thrombotic complications.

Hemolytic transfusion reactions in sickle cell anemia patients / Reações hemolíticas transfusionais em falcêmicos

Components of the sickle cell hemolytic transfusion reaction syndrome are related in this report. Also positive mechanisms involved in the development of post-transfusion anemia are described.

No relato são apresentados os componentes da síndrome hemolítica transfusional em pacientes portadores de anemia falciforme. Descrevo também os possíveis mecanismos envolvidos no desenvolvimento de anemia pós-transfusional.