Protective BCL11A and HBS1L-MYB polymorphisms in a cohort of 102 Congolese patients suffering from sickle cell anemia.

BACKGROUND: We aimed to investigate the distribution of selected BCL11A and HMIP polymorphisms (SNP's), and to assess the correlation with HPFH in a cohort of sickle cell patients. METHODS: A preliminary cross-sectional study was conducted in 102 patients. Group 1 was composed of patients with HPFH and Group 2 consisted of patients without HbF. We assessed 8 SNPs previously associated with HPFH in cohorts genetically close to the Congolese population. Observed frequencies were compared to expected frequencies. RESULTS: In the group 1, at rs7606173, the observed frequency for the genotype GG was significantly higher and the genotype GC was significantly lower than their respective expected frequencies. At rs9399137, the observed frequency of the genotype TT was significantly lower than expected. Conversely, the observed frequency of the genotype TC was significantly higher than expected. The observed frequency of the genotype TT at rs11886868 was significantly lower than the expected whereas the frequency of the genotype TC was significantly higher than observed. The lowest HbF level was recorded in patients with genotype CC at rs11886868. CONCLUSION: In this preliminary study, the results demonstrate that alleles of some of the 8 studied SNPs are not randomly distributed among patients with or without HPFH in this cohort.

Association between sickle cell anemia and alpha thalassemia reveals a high prevalence of the α3.7 triplication in congolese patients than in worldwide series.

BACKGROUND: Information about the association with alpha thalassemia in sickle cell patients is unknown in the Democratic Republic of Congo. There is very little data on the alpha thalassemia in patients suffering from sickle cell anemia in Central Africa, and their consequences on the clinical expression of the disease. METHODS: A cross-sectional study was conducted in 106 sickle cell patients living in the country's capital Kinshasa. The diagnosis of sickle cell anemia was confirmed with a molecular test using PCR-RFLP (restriction fragment length polymorphism) technique. The diagnosis of thalassemia was performed by the technique of multiplex ligation dependent probe amplification. RESULTS: The mean age of our patients was 22.4±13.6 years. The α3.7 heterozygous deletion, the α3.7 homozygous deletion and the α3.7 triplication were respectively encountered in 23.6%, 25.5% , and 11.3% of patients. Patients with normal αα/αα genotype represented 39.6% of the study population. The average of severe vaso-occlusive crises, the rates of blood transfusions per year, the rate of osteonecrosis, cholelithiasis and leg ulcers were significantly lower in the group of patients with α3.7 homozygous deletion and α3.7 triplication. CONCLUSION: The prevalence of α3.7 triplication was higher in sickle cell patients in the Democratic Republic of Congo than in worldwide series. The α3.7 triplication and α3.7 homozygous deletion were associated with less severe forms of the Sickle cell anemia in Congolese patients. These results showed the need to investigate systematically the alpha-globin gene mutations in sickle cell population in Central Africa.

Clinical and biological profile of Sickle Cell Anemia children in a rural area in Central Africa.

BACKGROUND: Sickle Cell Anemia (SCA) is the most common genetic disease worldwide caused by a single mutation in the gene HBB. The disease severity is very variable and depends on many factors. We evaluated the clinical and biological profile of sickle cell anemia children in rural Central Africa. METHODS: This cross-sectional study was conducted in the Hôpital Saint Luc de Kisantu, located 120 km away from Kinshasa-DR Congo in an area of 35 km around Kisantu with a population of roughly 80 000 individuals. We included SCA patients aged 6 months to 18 years. We collected clinical and hematological data. The SCA scoring system proposed by Adegoke et al. in 2013 was applied to determine the disease severity. We searched for factors associated to the disease severity. RESULTS: This study included 136 patients, 66 males and 70 females (sex-ratio M/F 0.94). The mean severity score was 8.21 ± 5.30 (ranges 0-23). Fifty-nine (43.4%) children had mild disease, 62 (45.6%) moderate and 15 (11%) severe disease. Girls had higher levels of HbF than boys (p = 0.003). An inverse correlation was observed between fetal hemoglobin and the disease severity (p = 0.005, r -0.239, IC95% -6.139; -1.469). Some factors such age influence the occurrence of certain chronic complications such as avascular bone necrosis. CONCLUSION: In conclusion, the disease severity of SCA depends on multiple factors. In this study, fetal hemoglobin was the main modulator of the disease severity. These data may also serve as a baseline to initiate HU treatment in this setting.

Sickle cell anemia and pregnancy: Profile of hemodynamic changes in sickle cell pregnant women in Kinshasa.

Pregnancy is accompanied by hormonal changes. These relate mainly to progesterone and placenate growth factor. Hemodynamic changes are also observed. in a sickle cell pregnant woman, all these changes have a direct effect on hypoxia. This is responsible for the polymerization of HbS. The latter causes the sickling of sickle red blood cells. sickling of red blood cells is responsible for hemolysis and vasoocclusion, two major acute manifestations during pregnancy in a sickle cell patient.

Hydroxyurea treatment for adult sickle cell anemia patients in Kinshasa.

Background: Despite a high incidence of sickle cell anemia, hydroxyurea (HU) treatment is rarely used in the DR Congo. This study aims to assess the efficacy of HU, the incidence of side effects that may limit its use in adults and to determine the dose needed for clinical improvement in patients. Methods: In a prospective study, patients received an initial dose of 15 mg/kg/day which was increased by 5 mg/kg every 6 months, up to a maximum of 30 mg/kg/day. The response and side effects to HU were evaluated biologically and clinically every 3 months during a 2-year period. Results: Seventy adult patients with a moderate or severe clinical phenotype initiated treatment. Only minor side effects were reported. At the end of the 2-year treatment phase, 45 (64.3%) had dropped out, of whom 33 were without a clear reason. Clinical and biological improvement was more marked during the first year. There was a reduction in severe vaso-occlusive crises (p < 0.001), need for transfusion (p < 0.001), and hospitalization days (p = 0.038). Fetal hemoglobin (HbF) levels increased on average 2.9 times after 12 months (p < 0.001). The increase in mean corpuscular volume was greater in the first year (p < 0.001) than in the second year (p = 0.041). The decrease in leukocytes (p < 0.001) was significant during the first year. In 70% of patients, the 20 mg/kg/day dose was needed to reach the 20% HbF threshold. Conclusion: HU is effective and well tolerated. The magnitude of the response varies from one patient to another. Improvement of clinical manifestations is achieved in most patients with a relatively low dose. Effective implementation of HU treatment will require improved adherence to treatment.

Sickle cell disease and pregnancy profile of complicated malaria in 982 pregnancies in Kinshasa.

INTRODUCTION: Malaria is associated with high morbidity during pregnancy. Homozygous sickle cell pregnant women are even more exposed during complicated malaria. The objective of the study was to evaluate the maternal and fetal morbidity of homozygous sickle cell pregnant pregnant women with complicated malaria. METHODS: We conducted a retrospective case-control study of 982 pregnancies in sickle cell pregnant women, during which a group of sickle cell pregnant women who received antimalarial chemoprophylaxis was compared to another group without chemoprophylaxis. We analyzed the clinical evolution of pregnant women (VOCs and transfusions, pregnancy weight gain) and parasite (parasite density at the time of diagnosis of complicated malaria and during treatment for three days). We analyzed the parameters of newborns at birth (age of pregnancy at the time of delivery, birth weight, weight of the placenta and histopathological examination of the placenta. RESULTS: Out of 982 pregnancies, 15% of pregnant women suffered from complicated malaria, 57% suffered from uncomplicated malaria and 28% did not suffer from malaria. Pregnancy weight gain, birth weight, was better in the group of pregnant women who received chemoprophylaxis and the placenta had less histological lesions. Parasite density was low. There was a significant positive correlation between parasite density and the number of CVOs and transfusions and between parasite density and histological lesions of the placenta and low birth weight. CONCLUSION: Complicated malaria is associated with high maternal and fetal morbidity in sickle cell patients. Malaria chemoprophylaxis can reduce maternal and fetal complications and parasite density during malaria infection.

Clinical and laboratory characterization of adult sickle cell anemia patients in Kinshasa.

BACKGROUND: Sickle cell anemia (SCA) is a monogenic hemoglobinopathy associated with severe acute and chronic complications, with the highest incidence worldwide in Sub-Saharan Africa. The wide variability in clinical manifestations suggest that a uniform response to hydroxurea may not be attained. In view of a potential treatment with hydroxyurea (HU), we assessed the variability of clinical and hematological manifestations in a cohort of adults with SCA in Kinshasa, capital of the DR Congo in Central Africa. METHODS: A cross-sectional study was conducted in a hospital dedicated to SCA management in Kinshasa. Clinical history of patients was recorded, a complete physical examination performed. The diagnosis was confirmed by means of DNA analysis. A full blood count and hemolysis markers were measured. The severity of the disease was evaluated by means of a previously reported score. RESULTS: The study group consisted of 166 genetically confirmed SCA patients. The SCA severity was mild in 28.9%, moderate in 64.5% and severe in 6.6%. The disease severity score increased with patient's age (p ≤ 0.001). The severity was higher in males compared to females (p = 0.012). In males, the severity score was correlated with the presence of priapism (p = 0.045), a manifestation not previously incorporated in the severity score. The severity score was inversely correlated with the fetal hemoglobin (HbF) rate (p = 0.005). Malnutrition (BMI <18.5 kg/m2) was present in 47% of patients and was related to the male sex, hip disease (aOR 3.11; p = 0.019) and severe phenotype (aOR 3.53; p = 0.012). Leg ulcers were more frequent in males than in females (p = 0.001; OR 24.3) and were correlated with the number of days of hospitalization (p = 0.029). Hip disease was related to the increasing age (p = 0.008). CONCLUSION: In this selected, hospital-based populations of adults with SCA, severe disease was rare, which may be due to survival bias. However, two thirds had moderate severity of the disease, mostly with a low HbF, and they may benefit from HU treatment. In the Central-African setting the separation between vaso-occlusive and hyperhemolytic sub-phenotypes was not applicable.

Homozygous Deletion Alpha-Thalassemia and Hereditary Persistence of Fetal Hemoglobin, Two Genetic Factors Predictive the Reduction of Morbidity and Mortality During Pregnancy in Sickle Cell Patients. A Report from the Democratic Republic of Congo.

OBJECTIVE: to determine the beneficial role of Fetal Hemoglobin (FHb) and alpha-thal on fetal and maternal morbidity during pregnancy in sickle cell patients. STUDY SITE: the study was conducted at the sickle cell center of Kinshasa between 2008 and 2018. SETTING AND STUDY POPULATION: this is a documentary and analytical study that included 980 deliveries of homozygous sickle cell patients. METHODS: the diagnosis of SCD and the quantification of FHb were performed with the capillary electrophoresis technique. The molecular test confirmed the diagnosis of SCD. The diagnosis of alpha-thal was made with the multiplex ligation-dependent probe amplification (MLPA) technique. Sickle cell pregnancies were followed according to the protocol of care in force in the University of Kinshasa Hospital service. The variables of interest were: hematological variables, sickle cell crises during pregnancy, maternal and fetal complications. STATISTICS: statistical analyses were performed with SPSS 20.0 software. Means and standard deviations were compared with the Student's t and ANOVA tests. The value of p <0.05 was considered the significance level. RESULTS: the Hb-SS / alpha-thal and HbSS / HPFH genotypes were observed in 101 and 121 women, respectively. Otherwise, 758 women had HbSS genotype. The morbidity related to sickle cell complications in the mother and fetus were less frequent in the Hb-SS / alpha-thal and HbSS / HPFH groups than in HB-SS group. The differences were statistically significant. CONCLUSION: this study showed a significant protective effect of alpha-thal and HPFH during pregnancy in sickle-cell pregnant women.

Correlation between the Lactate Dehydrogenase Levels with Laboratory Variables in the Clinical Severity of Sickle Cell Anemia in Congolese Patients.

BACKGROUND: Sickle cell anemia is an inflammatory disease and is characterized by chronic hemolysis. We sought to evaluate the association of lactate dehydrogenase levels with specific clinical phenotypes and laboratory variables in patients with sickle cell anemia. METHODS: The present cross-sectional study was conducted in Sickle Cell Centre of Yolo in Kinshasa, the Democratic Republic of Congo. Two hundred and eleven patients with Sickle Cell Anemia in steady state were recruited. Seventy-four participants with normal Hb (Hb-AA) were selected as a control group. RESULTS: The average rates of hemoglobin, hematocrit, and red blood cells tended to be significantly lower in subjects with Hb-SS (p<0.001). The average rates of white blood cells, platelets, reticulocytes and serum LDH were significantly higher in subjects with Hb-SS (p<0.001). The average rates of Hb, HbF, hematocrit and red blood cells of Hb-SS patients with asymptomatic clinical phenotype were significantly higher than those of the two other phenotypes. However, the average rates of white blood cells, platelets, reticulocytes, and LDH of Hb-SS patients with the severe clinical phenotype are higher than those of two other clinical phenotypes. Significant correlations were observed between Hb and white blood cell in severe clinical phenotype (r3 = -0.37 *) between Hb and red blood cells in the three phenotypes (r1 = 0.69 * r2 * = 0.69, r3 = 0.83 *), and finally between Hb and reticulocytes in the asymptomatic clinical phenotype and severe clinical phenotype (r1 = -0.50 * r3 = 0.45 *). A significant increase in LDH was observed in patients with leg ulcer, cholelithiasis and aseptic necrosis of the femoral head. CONCLUSION: The increase in serum LDH is accompanied by changes in hematological parameters. In our midst, serum LDH may be considered as an indicator of the severity of the disease.