The spectrum of splenic complications in patients with sickle cell disease in Africa: a systematic review

The majority of the global population of sickle cell disease (SCD) patients resides in Africa. Individuals with this condition are at great risk of serious infections and early mortality secondary to splenic dysfunction without preventative measures. This review investigated the spectrum of splenic complications encountered in SCD among populations in Africa. We systematically searched several databases for all articles published through March 3, 2020. We included 55 studies from 14 African countries. This review reveals the difference in frequency of splenic complications in SCD in Africa when compared with their counterparts in the United State and Europe. While several studies (n = 45) described splenomegaly with a prevalence of 12% to 73% among children, and 4% to 50% among adults with HbSS, the reported prevalence for acute splenic sequestration crisis (n = 6 studies) and hypersplenism (n = 4 studies) was <10% and <5% respectively. A total of 30 surgical splenectomy was reported across eight studies. Only two (3.7%) studies provided data on spleen function. A conflicting pattern was observed amongst studies that evaluated the relationship between splenomegaly and the presence of bacterial and malaria infections. This review reveals the paucity of studies describing the role of SCD‐induced splenic dysfunction in morbidity and infection related mortality in Africa

Comparative study of the growth and nutritional status of Brazilian and Nigerian school-aged children with sickle cell disease

Background: Comparative studies of patients in different sociogeographic/ecological zones may unravel potential environmental and nutritional factors influencing disease phenotype. In sickle cell disease (SCD), differential access to comprehensive care may influence their growth and nutritional status. Methods: From June 2015 to February 2016, steady-state nutritional parameters of 109 Brazilian and 95 Nigerian children with SCD attending routine clinic visits at Universidade Federal de Sao Paulo, Brazil and Obafemi Awolowo University Teaching Hospital, Ile-Ife (Ilesa unit), respectively, were compared. Results: A relatively high proportion of the children in both centres (23.5%) were wasted [body-mass index (BMI)-for-age z-score<-2). BMI-for-age z-score, height-for-age z-score, upper arm fat area and fat percentage were lower in the Nigerian cohorts. More Nigerians, 29.5% (28/95) against 18.3% (20/109) were wasted, and had short stature, [12.6% (12/95) vs. 3.7% (4/109)] than Brazilians. A higher proportion of Brazilian patients were overweight or obese (9.2 vs. 4.3%), and taller for age (15.6 vs. 8.4%). None of the Nigerian patients had severe vitamin D deficiency, only 12.6% (12/95) had suboptimal vitamin D and 1.1% (1/95) had low serum zinc levels, unlike 79.8% (87/109) of the Brazilian patients with suboptimal vitamin D and 10.1% (11/109) with low zinc. Conclusion: Undernutrition is still prevalent among the two cohorts. Nigerian patients were thinner and had reduced linear growth for age. This observation justifies the continued need for specialized nutritional care for children with SCD. In addition to hydroxyurea therapy, research is needed to determine appropriate nutritional intervention and exercise regimens for these children.CNPqUniv Fed Sao Paulo, Escola Paulista Med, Haematol & Blood Transfus Div, Sao Paulo, BrazilObafemi Awolowo Univ, Dept Pediat & Child Hlth, Ife, NigeriaKuwait Univ, Fac Med, Dept Paediat, Kuwait, KuwaitUniv Fed Sao Paulo, Escola Paulista Med, Dept Pediat, Sao Paulo, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Haematol & Blood Transfus Div, Sao Paulo, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Dept Pediat, Sao Paulo, BrazilCNPq: 159581/2014-1Web of Scienc

Uridine diphosphate glucuronosyl transferase 1A (UGT1A1) promoter polymorphism in young patients with sickle cell anaemia: report of the first cohort study from Nigeria

(TA) n repeat sequence (rs8175347) of UGT1A1 gene promoter polymorphism is associated with serum bilirubin levels and gallstones among different sickle cell anaemia (SCA) populations. There are no data on UGT1A1 polymorphisms and their impact on Nigerian SCA patients. In this study, we determined the distribution of the UGT1A1 (TA) n genotypes among a group of young Nigerian SCA patients and healthy controls. In addition, the influence of UGT1A1 (TA) n genotypes on the laboratory and clinical events among the patients was determined. Methods The distribution of the UGT1A1 (TA) n genotypes among 101 young Nigerian SCA patients and 64 normal appropriate controls were determined and studied. The UGT1A1 (TA) n genotypes were further classified into subgroups and used to differentiate the clinical events and laboratory parameters of the patients. Results Four (TA) n alleles:(TA)5, 6, 7, and 8 were found. These were associated with 10 genotypes: TA5/5, 5/6, 5/7, 5/8, 6/6, 6/7, 6/8, 7/7, 7/8, 8/8. The normal (wild-type)-(TA) 6/6), low- (TA) 7/7, 7/8, 8/8), intermediate- (TA) 5/7, 5/8, 6/7, 6/8), and high-activity (TA) 5/5, 5/6,) genotypes were found in 24.8, 24.8, 41.5, and 8.9% patients and 20.3, 15.6, 61, and 3.1% controls respectively. The general genotype distribution of the patients and control group were not significantly different. There were significant differences in serum bilirubin and lactate dehydrogenase (LDH) of the patients when differentiated by the UGT1A1 (TA) n genotypes (p<0.05). Asymptomatic gallstones were found in 5.9% of patients and were significantly of the low-activity genotypes sub-group 5 (20%) vs 1(1.3%) p = 0.0033. Although, bilirubin and fetal hemoglobin (HbF) of patients with gallstones were significantly different from those without gallstone, only the serum bilirubin was associated with UGT1A1 (TA) n genotypes on multivariate analysis (p < 0.0001). Conclusion This study highlights the contribution of UGT1A1 polymorphisms, a non-globin genetic factor, to the laboratory and clinical manifestations of young Nigerian SCA patients for the first time. It also shows that children with co-inheritance of low UGT1A1 (TA) n affinity genotypes may be at risk of gallstone, hence the need to follow them up20CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP2015/141693–02014/00984–

Evaluation of two red cell inclusion staining methods for assessing spleen function among sickle cell disease patients in North-East Nigeria

Introduction The loss of splenic function is associated with an increased risk of infection in sickle cell disease (SCD); however, spleen function is rarely documented among SCD patients in Africa, due partly to the non-availability of sophisticated techniques such as scintigraphy. Methods of assessing splenic function which may be achievable in resource-poor settings include counting red blood cells (RBC) containing Howell Jolly Bodies (HJB) and RBC containing silver-staining (argyrophilic) inclusions (AI) using a light microscope. We evaluated the presence of HJB - and AI - containing RBC as markers of splenic dysfunction among SCD patients in Nigeria. Methods We prospectively enrolled children and adults with SCD in steady state attending outpatient clinics at a tertiary hospital in North-East Nigeria. The percentages of HJB- and AI-containing red cells were estimated from peripheral blood smears and compared to normal controls. Results There were 182 SCD patients and 102 healthy controls. Both AI- and HJB-containing red cells could be easily identified in the participants blood smears. SCD patients had a significantly higher proportion of red cells containing HJB (1.5%; IQR 0.7% - 3.1%) compared to controls (0.3%; IQR 0.1% - 0.5%) ( P = 0.0001). The AI red cell counts were also higher among the SCD patients (47.4%; IQR 34.5% - 66.0%) than the control group (7.1%; IQR 5.1% - 8.7%) ( P = 0.0001). The intra-observer reliability for assessment of HJB-(R = 0.92; R 2 = 0.86) and AI-containing red cells (R = 0.90; R 2 = 0.82) was high. The estimated intra-observer agreement was better with the HJB count method (95% limits of agreement, −4.5 to 4.3; P = 0.579). Conclusion We have demonstrated the utility of light microscopy in the assessment of red cells containing - HJB and AI inclusions as indices of splenic dysfunction in Nigerian SCD patients. These methods can be easily applied in the routine evaluation and care of patients with SCD to identify those at high risk of infection and initiate appropriate preventive measures

Ultrasonographic Splenic Indices Among Paediatric and Adults with Sickle Cell Disease in Nigeria

Background Ultrasonography is an established and reliable method for assessing the spleen. Because of variation due to genetic and other environmental factors including malaria endemicity, interpretation of splenic sizes requires a knowledge of the normal reference range for a given population. The aim of this study was to determine spleen size in different age groups among healthy people in North-Eastern Nigeria and use this as a reference to determine spleen size amongst sickle cell disease (SCD) patients. Methods Using a cross-sectional study design, spleen size was measured in healthy people of different age groups, and steady-state SCD patients (children and adults) using abdominal ultrasonography. Using the age-group specific reference values obtained from the controls, spleens were classified into small, normal size, or enlarged among the SCD patients. Results Abdominal ultrasonography was performed for 313 participants, comprising 109 (34.8%) healthy controls and 204 (65.2%) steady-state SCD patients. The spleen was visualized in all the controls. However, 97(47.6%) of the SCD patients had no visible spleen. Small, normal, and enlarged spleens were observed in 16.7% (n=18/107), 63.6% (n=68/107) and 19.6% (n=21/107) SCD patients, respectively. Compared to the control group, splenic length was three-fold higher in the first two years of life in SCD patients, followed by a progressive age-related decline in size. Enlarged spleens were detected among 5(2.4%) SCD patients by manual palpation method compared to 21 (19.6%) using ultrasonography. Conclusion Model-based age-specific reference ranges and percentile curves for splenic dimensions based on ultrasonography among normal controls in North-Eastern Nigeria were established and may be of value in assessing spleen sizes among SCD patients living in malaria-endemic regions of Africa. Regular spleen scans to assess changes in size can help identify SCD patients at risk of splenomegaly complications including subclinical acute sequestration and hypersplenism, and those who are developing splenic atrophy

Clinical and Laboratory Factors Associated with Splenic Dysfunction Among Sickle Cell Disease Patients in a malaria endemic region

Background Although loss of splenic function is the expected natural course for individuals with sickle cell disease (SCD), factors such as high HbF and coexistence of alpha thalassemia may ameliorate this process. We evaluated factors associated with two surrogate markers of spleen dysfunction - Howell-Jolly bodies (HJB) and argyrophilic inclusion (AI) red cell counts among SCD patients. Methods Cross-sectional data of 182 SCD patients (median age 11 years;1- 45 years) and 102 normal controls (median age 12 years;1-32 years) were evaluated. Blood tests including full blood count, serum chemistry and HPLC were performed. The HJB and AI red cell counts were performed on peripheral blood smears. Results The percentages of HJB- and AI- red cells rose significantly with increasing age in the SCD group. On regression analysis, frequency of HJB red cells associated positively with MCH (β = 0.289; P = 0.001) and negatively with HbF (β = -0.259; P = 0.002). The AI red cell counts also associated positively with MCH (β = 0.321; P=0.001) and negatively with HbF (β = -0.242; P = 0.020). Conclusion Data from this study indicates that the negative association of HbF with both markers of splenic dysfunction among our SCD patients residing in a malaria-endemic region is similar to findings elsewhere of its ameliorating effect on splenic dysfunction

Determinants of splenic preservation among patients with sickle cell disease in North‐Eastern Nigeria

Objective: In patients with sickle cell disease (SCD), the spleen commonly enlarges during early childhood, but undergoes reduction in size and fibrosis from repeated episodes of vaso‐occlusion and infarction. The rate of progression of this process varies markedly among these patients. The aim of current study was to explore clinical and laboratory factors associated with the preservation of the spleen among these patients. Methods: Two hundred four patients with SCD (103 females; age 1–45 years) underwent abdominal ultrasonography at the University of Maiduguri Teaching Hospital, Nigeria between October 2020 and November 2021 to assess for splenic visualisation and echotexture. Steady‐state clinical parameters and blood samples for full blood count, serum chemistry, high‐performance liquid chromatography and malaria parasitemia were obtained from all the patients. Results: The spleen was visualised in 107 (52.4%; 95% confidence interval [CI], 46%–59%) patients with SCD on ultrasonography. While the spleen was visualised in all children less than 5 years of age, it was visualised in only 23.5% of those aged 15 years and older. Visualisation of the spleen was significantly associated with low mean corpuscular haemoglobin concentration and high haemoglobin F (HbF) in those younger than 10 years. The odds of visualisation of the spleen on ultrasonography increased by a factor of 1.17% for every 1% increase in HbF level. Only 32 (15%) patients were on regular hydroxyurea therapy. The HbF level was significantly higher among patients on hydroxyurea (median 12.7 vs. 7.4; p < 0.0001). Conclusion: In patients with SCD, failure to visualise the spleen was not found in children less than 5 years old. Patients with visualised spleens had a higher level of HbF than those with non‐visualised spleens. HbF was significantly associated with visualisation of the spleen before 10 years of age. Since early administration of hydroxyurea will increase HbF level, we expect that it would help to preserve the spleen

Ultrasonographic assessment of spleen size and pattern of change among sickle cell disease patients and healthy controls in North-Eastern Nigeria

Background: Ultrasonography is an established and reliable method for assessing the spleen. Because of variation due to genetic and other environmental factors including malaria endemicity, interpretation of spleen sizes requires a knowledge of the normal reference range for a given population. This study aimed to identify spleen size reference ranges across age groups of healthy controls to serve as a baseline to assess changes in spleen size in patients with sickle cell disease. Methods: Using a cross-sectional study design, spleen size was measured in healthy people of different age groups and steady-state sickle cell disease patients (children and adults) using abdominal ultrasonography. Using the age-group-specific reference values obtained from the controls, spleens were classified into small, normal size or enlarged among the sickle cell disease patients. Results: The study consisted of 109 (34.8%) healthy controls and 204 (65.2%) steady-state sickle cell disease patients. The spleen was visualised in all the controls ( n = 109) and in 107 (52.4%) sickle cell disease patients. Using cut-off values for spleen length among the controls across age groups (&lt; 5 years (5.0–7.0 cm); 5–9 years (5.5–8.5 cm); 10–14 years (6.0–11.0 cm) and ⩾ 15 years (7.0–12.5 cm)), spleen size was classified as small ( n = 18/204; 8.87%), normal ( n = 68/204; 33.3%) and enlarged ( n = 21/204; 10.3%) among the sickle cell disease patients. Conclusion: Model-based age-group reference ranges and percentile curves for splenic dimensions based on ultrasonography among normal controls in North-Eastern Nigeria were established and may be of value in assessing spleen sizes among sickle cell disease patients living in malaria-endemic regions of Africa