Fetal hemoglobin in sickle cell anemia: Saudi patients from the Southwestern province have similar HBB haplotypes but higher HbF levels than African Americans (original) (raw)
Related papers
Sickle Cell Disease Subphenotypes in Patients From Southwestern Province of Saudi Arabia
Sickle cell disease (SCD) is common in the Eastern and Southwestern (SW) Provinces of Saudi Arabia. We studied 159 patients with SCD to better characterize its phenotype in the SW Province, where patients usually have a HBB haplotype of African origin. All cases had history and examination, chart review, and laboratory testing. Blood tests were obtained during steady state and included: complete blood count, reticulocytes, hemoglobin electrophoresis, lactate dehydrogenase, and G6PD level. HBB haplotype and presence of a-thalassemia were also determined. Frequency of various SCD complications was as follows: painful episodes of variable severity occurred in majority of patients (98%), osteonecrosis (14%), acute chest syndrome (22%), splenic sequestration (23%), gallstones (34%), stroke (7.5%), priapism (2.6%), serious infections (11.5%), and persistent splenomegaly (11%) beyond 5 years of age. No patient had leg ulcer. History of asthma and high steady state white blood cells count were associated with increased risk of acute chest syndrome. Coinheritance of a-thalassemia was associated with a lower frequency of gallstones. Higher fetal hemoglobin level was associated with persistent splenomegaly but not with other complications. Splenic sequestration was more common among males and was associated with lower steady state hemoglobin. SCD phenotype in the SW Province is variable and comparable with African Americans except for the rarity of priapism and the absence of leg ulcers. Fetal hemoglobin level was not associated with SCD vaso-occlusive complications. New genetic modifiers and environmental factors might modulate the phenotype of SCD in Saudi Arabia.
British Journal of Haematology, 2014
Sickle cell disease (SCD) in Saudi patients from the Eastern Province is associated with the Arab-Indian (AI) HBB (b-globin gene) haplotype. The phenotype of AI SCD in children was described as benign and was attributed to their high fetal haemoglobin (HbF). We conducted a hospital-based study to assess the pattern of SCD complications in adults. A total of 104 patients with average age of 27 years were enrolled. Ninety-six per cent of these patients reported history of painful crisis; 47% had at least one episode of acute chest syndrome, however, only 15% had two or more episodes; symptomatic osteonecrosis was reported in 18%; priapism in 17%; overt stroke in 6%; none had leg ulcers. The majority of patients had persistent splenomegaly and 66% had gallstones. Half of the patients co-inherited a-thalassaemia and about one-third had glucose-6-phosphate dehydrogenase deficiency. Higher HbF correlated with higher rate of splenic sequestration but not with other phenotypes. The phenotype of adult patients with AI SCD is not benign despite their relatively high HbF level. This is probably due to the continued decline in HbF level in adults and the heterocellular and variable distribution of HbF amongst F-cells.
Hematology & Transfusion International Journal, 2016
Background: Sickle Cell Anemia (SCA) is the most common monogenic disorder that is inherited as an autosomal recessive pattern. Fetal hemoglobin (HbF) plays a major role in ameliorating clinical severity of the SCA where higher expression of HbF is associated with a reduction in the painful episode and thus reduces the number of hospitalization. The current work aimed to investigate the effect of high HbF in SCA adult patients in Makkah city, Western Saudi region who visited Al-Noor Specialist Hospital. Methodology: Blood samples in EDTA tubes were collected from 80 SCA adults patients during the period of February, 2015 to April, 2016. Hematological analyses including Complete Blood Cell Count (CBC) and reticulocyte count were performed to assess anemia status. Hemoglobin quantification and separation was performed using High Pressure Liquid Chromatography (HPLC). Patients with hydroxyl urea intake were excluded from the study due to its elevation effect on HbF level. Result: Of the 80 studied patients, 60(75%) showed an increased level of HbF above the upper normal limit with a mean of 6.01% +/-3.5. The increase level of HbF was more than 10%, 5-10%, and less than 5% in 6(10%), 24(40%) and 30(50%) patients respectively. A significant association between high HbF and red cell parameters was observed in patients with higher HbF than 10% compared to the other two groups. Conclusion: High HbF gives an advantage to the SCA patients where it has an ameliorating effect on the severity and the complications of the disease. The elevated HbF in Makkah city is high among adult SCA patients (75%) but the average expression level is lower than other Saudi regions. This indicates patients from Makkah City have more clinical severity and thus highly attended healthcare is required to minimize disease effect and its complication. Further molecular studies are recommended to find out genetic determinants such as single nucleotide polymorphisms of high HbF expression in SCA.
Journal of Natural Science, Biology and Medicine, 2015
Background: Notwithstanding, the growing incidence of sickle cell hemoglobinopathies (SCH) such as sickle cell anemia (SCA) or sickle cell disease, sickle/beta-thalassemia; the exact prevalence remains obscure in Saudi Arabia. Hence, this study is an attempt to determine the frequency of SCA and sickle cell trait (SCT) among all anemic patients with SCH treated at the King Abdul-Aziz Medical City (KAMC), Riyadh, Saudi Arabia. Furthermore, the hemoglobin (Hb) S and other Hb patterns (Hb AS and Hb F) were also estimated in SCA and SCT patients. Materials and Methods: Results of Hb capillary electrophoresis performed on all patients with SCH from January 2011 to December 2013 were evaluated retrospectively. Results: Of a total of 3332 patient data analyzed, 307 were anemic patients (58% males and 42% females) with SCH. The sickling test showed all the patients to be positive. Hb electrophoresis revealed the incidence of 96.7%, 3.3%, and 0% of the patients suffered from SCA, SCT and sickle/ beta-thalassemia, respectively. Patients with SCA had a higher level of Hb F and showed no crisis when compared with other SCA patients who had lower or no Hb F levels. Conclusion: SCA is relatively frequent among males (56.4%) than females out of all patients with SCH. The SCA incidence was more common (48.5%) among children, frequency of SCT among adult age group was 1.6%, while sickle/beta-thalassemia was 0%.
Pharmacogenomics and Personalized Medicine
Sickle cell disease (SCD) is a genetic disease influenced by ethnicity and regional differences in its clinical course. Recent advances in the management of SCD with newer therapies are being introduced to the Western population. However, many of these treatments are yet to be used in the Arabic SCD population. Understanding the genetic variations of SCD regionally is essential to anticipate the utilization of new treatments. This systematic review's main objective is to pool the available data on the genetic composition of SCD in the Arabic population. Data for 44,034 patients was extracted from 184 studies (11 case reports, 8 case series, 56 retrospectives, 107 prospective observational studies, and 2 clinical trials) using PubMed, Scopus, and Google Scholar. Male (49%) and female (51%) patients were equally reported wherever gender was available (N=13105). Various SCD genotypes were reported in a total of 14,257 patients, including Hb SS (77%) Hb Sβ0 (9.9%), and Hb Sβ+ (7.2%), while the rest of the genotypes, including HbSC, HbSD, HbSE, HbSO Arab, Hb S/α-Thal, Hb Sβ0 + α-Thal, and HBS Oman were individually reported in <4% of the cases. Major SCD complications in the Arab population included pain crises (48.25%) followed by neurological complications (33.46%), hepatobiliary complications (25.53%), musculoskeletal complications (24.73%), and hemolytic anemia (23.57%). The treatments reported for SCD included hydroxyurea (20%), blood transfusion (14.32%), and Deferasirox (3.03%). We did not find the use of stem cell transplantation or newer treatments such as L-Glutamine, Voxelotor, Crizanlizumab, or gene therapy reported in any of the studies included in our review. This review highlights the genetic makeup of SCD in Arab countries and its common phenotypic manifestations and will help direct further research on SCD in this region, especially concerning genetic therapy.
Blood Cells Molecules and Diseases, 2020
This study was aimed to identify the predictors of splenic sequestration crisis (SSC) among pediatric patients with sickle cell disease (SCD). This prognosis study was carried out in the pediatric immuno-hematology unit, over 20 years (1998 to 2017), enrolling patients with SCD. The cox model was used in multivariate analysis. Among 423 patients with SCD (240 S/S phenotype, 128 S/B0, 30 S/B+, 14 S/O arab and 11 S/C), 150(35.4%) had at least one episode of SSC. The average age of patients at the first episode was 48.3 months ± 32.4(2-168). Recurrence of SSC was observed in 117 patients (78%). Spleen size ≥3 cm at baseline was the strongest predictor of SSC occurrence (HR = 7.27, CI: 4.01-13.20, p = 0.05) and recurrence (HR = 6.37, CI: 1,46-27.83, p = 0.01). Pallor revealing the disease, age at onset of symptoms < 24 months and reticulocytosis ≥300,000/mm 3 increased the risk of SSC. Pain crisis revealing the disease as well as neutrophilia was associated with a lower risk of SSC. In conclusion, this study confirmed the high prevalence of SSC in SCD and the high frequency of recurrence after a first episode. The SSC occurrence and recurrence were intimately linked to the presence of splenomegaly, chronic pallor revealing the disease as well as reticulocytosis. This study, conducted in a pediatric population with SCD in a reference center for hemoglobinopathies, was aimed to evaluate the frequency of SSC and to identify the predictive factors of SSC occurrence and recurrence among patients with SCD.
International Journal of Laboratory Hematology, 2016
Bahrain has high prevalence rates of sickle cell and thalassemia in the population. This study reports the frequencies and phenotypic characteristics of aand/or b-thalassemia associated with sickle-cell disease (SCD) in a tertiary care hospital. Methods: Adult SCD patients (n = 200) were screened for the common aand b-thalassemia alleles prevalent in the region using molecular techniques. Results of CBC, hemoglobin analysis, and average annual frequencies of severe pain episodes and numbers of transfused red cell units were documented. Results: Patients were grouped on the basis of molecular studies as sickle-cell anemia (SS, n = 131), SS/a-thalassemia with three normal genes (n = 27), SS/a-thalassemia with two normal genes (n = 11), sickle-b-thalassemia (Sb, n = 23), and Sb with co-inherited a-thalassemia (n = 8). Identified a-thalassemia determinants were Àa 3.7 (n = 52), Àa 4.2 (n = 4), a T-Saudi a (n = 1), and a Hph a (n = 1). All b-thalassemia alleles were b 0 defects. Sickle-thalassemia association resulted in higher hemoglobin, hematocrit, and erythrocyte counts with reduced MCV and reticulocytes. Significant clinical associations were as follows: increased severe pain frequency with a-thalassemia (three-gene group); red cell transfusion with b-thalassemia alleles and female gender. Conclusion: One-third of patients with SCD co-inherited aand/or b-thalassemia alleles and these associations explained some of the observed phenotypic variability. A low prevalence of nondeletion a-thalassemia alleles was observed in these patients. The most significant disease amelioration occurred in SCD associated with two a-thalassemia alleles.