Informant discrepancy in perceptions of sickle cell disease severity

OBJECTIVES: To evaluate whether informants (children, caregivers, and physicians) differ in their perceptions of chronic disease severity and the extent to which these differences can be explained by objective indices of disease severity, and adjustment of the caregiver. METHODS: Participants were 58 children and adolescents between the ages of 8 and 18 years diagnosed with sickle cell disease. Information on perceptions of disease severity, caregiver adjustment, and biological markers of disease severity was obtained at a routine clinic follow-up appointment. RESULTS: Analyses indicated significant differences in perceptions of disease severity. Psychological adjustment of the caregiver and biological indices of disease severity were significant predictors of these differences. CONCLUSION: Implications for the association between chronic disease and adjustment are discussed.     

Relationship of structural magnetic resonance imaging, magnetic resonance perfusion, and other disease factors to neuropsychological outcome in sickle cell disease

OBJECTIVE: To investigate the relationship between neuropsychological functioning and radiographic findings in children with sickle cell disease (SCD) with no history of clinical neurological events. METHODS: Thirty-one patients with SCD randomly selected from a regional treatment center underwent neuropsychological and disease severity assessments. Of these, 22 also had structural magnetic resonance imaging and magnetic resonance perfusion studies performed. RESULTS: Forty-five percent of the imaged subgroup showed imaging abnormalities that were found to be correlated with disease severity but not neuropsychological level of performance indices. A significant relationship, however, was found between imaging abnormalities and increased variability in neuropsychological performance. CONCLUSIONS: These results corroborate the high rate of rheologic and vascular pathology in SCD and underscore the importance of representing neuropsychological functioning in multiple ways.     

Association between Duffy antigen receptor for chemokines expression and levels of inflammation markers in sickle cell anemia patients

Since inflammation plays a prominent role in the pathogenesis of sickle cell anemia (SCA) and Duffy antigen receptor for chemokines (DARC) modulates the function of inflammatory processes, we analyzed the relationship between the erythrocyte DARC phenotype and clinical expression of SCA. DARC locus was genotyped in 212 SS adult patients followed by the sickle cell center of Guadeloupe (French West Indies). After patients' stratification according to RBC DARC expression, the prevalence of renal disease, leg ulcers, priapism and osteonecrosis was compared between patient groups as well as hematological variables and plasma levels of chemokines. Duffy-positive patients exhibited higher counts of white blood cells (9.95 ± 2.36 vs 8.88 ± 2.32 10⁹/L, p = 0.0066), polynuclear neutrophils (5.1 ± 1.73 vs 4.51 ± 1.71 10⁹/L, p = 0.0227), higher plasma levels of IL-8 (4.46 ± 1.22 vs 1.47 ± 0.5 pg/mL, p = 0.0202) and RANTES (27.8 ± 4.3 vs 18.1 ± 2.3 ng/mL, p = 0.04) than Duffy-negative patients. No association was detected between RBC expression of DARC and the studied complications.     

Factors that influence adolescent adaptation to sickle cell disease

OBJECTIVE: To examine whether psychosocial factors play a more important role than biomedical risk factors in predicting adolescent adaptation to sickle cell disease (SCD); to determine whether psychosocial factors moderate the relationship between biomedical risk factors and adaptation. METHODS: Ninety African American adolescents from the multisite Cooperative Study of Sickle Cell Disease were recruited to complete a battery that included measures of psychosocial status and psychological adaptation. Data regarding their health status were collected from medical records. RESULTS: The findings revealed that intrapersonal (self-esteem, social assertiveness), stress-processing (use of social support), and social ecological factors (family relations) were significant predictors of adaptation; however, biomedical factors did not predict adaptation. There was no evidence that psychosocial factors moderated the relationship between biomedical risk factors and adaptation. CONCLUSIONS: Psychosocial factors proved to be better predictors of adaptation than biomedical risk factors. Additional research is needed to better understand the nature of the interrelationships among biomedical risk factors, psychosocial factors, and adaptation.     

Benign sickle cell disease in Saudi Arabia: survival estimate and population dynamics

A survey of 8,084 adult Saudi male employment applicants yielded 872 with the sickle cell trait (AS) and 51 with sickle cell disease. Based on the known distribution of hemoglobin S genes between oasis and non-oasis populations in Saudi Arabia, and on calculation of the expected number of abnormal homozygotes within the non-oasis and oasis subgroups as well as the entire employment applicant group, it appears that virtually 100% of Saudis with SS disease survive to adult life. Saudi Arabs and other Caucasian populations in the Middle East exhibit a benign type of SS disease as compared with Blacks in Africa and the Americas. In the Middle East, gene contributions from SS individuals will shift equilibrium frequencies to higher levels than encountered in Black populations under sustained selective pressures, and the polymorphism will tend to be stable with decline in selective pressure. There are some indications that the hemoglobin S gene may have been a recent import into the Middle East.     

Brief report: Academic attainment in children with sickle cell disease

OBJECTIVE: To examine the impact of sickle cell disease (SCD) on academic attainment; the relation between academic attainment and achievement in SCD; and determinants of attainment in SCD. METHODS: Children with SCD and demographically matched peers were compared on academic attainment. Hematocrit, illness frequency, cognitive ability, and socioeconomic status were used to model the predictors of attainment problems. RESULTS: Attainment problems were more frequent in children with SCD (> or =31% vs. 14%). A significant number of children showed difficulties with only attainment or academic achievement. Cognitive ability was a strong predictor of both academic outcome measures. Illness-related school absences predicted academic attainment but not achievement. CONCLUSIONS: Academic attainment is affected by SCD. Tests of academic achievement are meaningful predictors of functional impairments for children with SCD; however, school outcomes are best evaluated with both achievement and attainment measures.     

Cognitive functioning in children with sickle cell disease: a meta-analysis

OBJECTIVE: To establish whether sickle cell disease (SCD) affects cognitive functioning in children with no evidence of cerebral infarction. METHODS: We conducted a meta-analysis of studies of cognition in SCD to determine the size of any statistical difference between children with SCD and controls. Methodological factors were evaluated according to the size and frequency of group differences. RESULTS: There were small but reliable decrements in cognitive functioning on IQ measures (4.3-point difference overall). The most methodologically rigorous studies showed a highly similar pattern. Sampling issues associated with the effect size for IQ were identified. Measures of specific abilities appear more sensitive than IQ scores to cognitive decrements in SCD. CONCLUSIONS: SCD is associated with cognitive effects even in the absence of cerebral infarction. The causes of this cognitive decrement may include direct effects of SCD on brain function or indirect effects of chronic illness.     

Relationship between disease severity and folate status of children with sickle cell anaemia in Enugu,South East Nigeria

BackgroundRepeated crises in children with sickle cell anaemia (SCA), which is a manifestation of disease severity, results in depletion of their minimal tissue folate stores, with higher likelihood of folate deficiency. The study aimed to determine the relationship between disease severity and the folate status of children with SCA attending University of Nigeria Teaching Hospital (UNTH), Enugu.MethodsThis was a hospital based, cross-sectional study conducted between September 2018 and March 2019. One hundred participants were recruited, consisting of 50 children having sickle cell crisis and 50 age and gender matched haemoglobin AA genotype controls. Relevant information was documented using a pretested questionnaire. Sickle cell severity score was determined using frequency of crisis, admissions and transfusions in the preceding one year, degree of liver and splenic enlargement, life-time cummulative frequency of specific complications of SCA, leucocyte count and haematocrit.ResultsFolate deficiency was observed in eight percent of the subjects and none of the controls. The difference was not significant (Fisher''s exact = 4.167, p=0.117). The odds of being folate deficient was 8.5 times more likely during anaemic crisis than in vaso-occlusive crisis, though not significant (95% C.I 0.05 – 89.750, p = 0.075). The mean SCA severity score was 8.06 ± 3.64, signifying a moderate SCA severity in the study population. There was a no relationship between folate status and severity of SCA (Fisher''s exact = 0.054, p = 0.949)ConclusionFolate status in children with SCA is not affected by their disease severity. Therefore, there may be no need for additional folate supplementation with increasing severity of sickle cell anaemia.     

Parent factors and adolescent sickle cell disease: associations with patterns of health service use

OBJECTIVE: To examine relationships among parent characteristics (parent-adolescent relationship, parents' illness knowledge, and parents' perceptions of illness-related burden) and use of routine and urgent health services among adolescents with sickle cell disease (SCD). METHOD: Seventy adolescents, ages 12-18, and their parents completed questionnaires assessing illness knowledge, perceptions of illness burden, parent-adolescent relationships, and adolescents' psychological functioning. Information about pain, routine services (i.e., care at home, clinic visits) and urgent service use (i.e., emergency department visits, hospitalizations) was obtained from parents and medical records. RESULTS: After we controlled for disease severity and life events, parents' perception of more illness-related stress was the strongest predictor of both types of service use. Greater parental knowledge about SCD also related to higher frequency of routine service use. Disease severity was strongly associated with frequency of urgent service use. CONCLUSIONS: Both parent characteristics and disease severity were associated with patterns of service use. Enhancing aspects of parental functioning may help families make adaptive decisions regarding health care services for SCD pain management.     

HLA-G polymorphism influences the susceptibility to HCV infection in sickle cell disease patients

Despite its well known monogenic etiopathogenesis, sickle cell disease (SCD) is characterized by a striking variability of clinical presentation. There is growing evidence that genetic factors may be involved in this variability. Human leukocyte antigen (HLA)-G is a non-classical HLA molecule which was shown to be expressed at sites of inflammation and in inflammatory diseases. Besides its large and highly polymorphic promoter region, the 3' UTR region seems also to play an important role on regulating HLA-G expression. We investigated the influence of the 14 pb (rs1704) and the +3142 (rs1063320) HLA-G polymorphisms in 93 SCD patients in order to evaluate its potential role on clinical parameters. Twenty-one patients presented an HCV infection. Among all SCD patients 16 (22.2%) were homozygous for the +3142C genotype, none of them hepatitis C (HCV) positive. Controlling for blood transfusions in the last year, the C allele represented a dose dependent protection effect for HCV infection (PR = 0.41; 95% CI: 0.24–0.71). The +3142C allele was also underrepresented among patients with history of respiratory-tract infections. Our results support a role of the +3142 polymorphism in the susceptibility to infections, in particular to HCV infection, and suggest a possible interference of the HLA-G molecule in the response to infections, among SCD patients.     

Parental report of health-related quality of life in children with sickle cell disease

Health-related quality of life (HRQOL) of youths with sickle cell disease (SCD) has not been described, despite the psychosocial and physical consequences associated with the disease. We compared the HRQOL of 58 children with SCD to a demographically similar sample of 120 healthy children and examined predictors of HRQOL. Child HRQOL was assessed using the Child Health Questionnaire--Parent Report Form. Review of medical charts of children with SCD provided data on disease-related complications. Results demonstrated that caregivers of children with SCD reported that their children had more limited physical, psychological, and social well-being than healthy children. Older child age, female gender, and more disease-related complications predicted limitations in the physical health of children with SCD. The findings indicated that SCD significantly affects the HRQOL of youths. Certain subgroups of patients (e.g., children with more disease complications) may benefit from interventions specifically designed to improve their physical functioning.     

Acute leukemia in sickle cell disease patients in a tertiary health facility in Nigeria: a case series

Background and objectivesSickle cell disease(SCD) is a disorder of red cells resulting from the co-inheritance of haemoglobin S (HbS) with another abnormal haemoglobin. The diagnosis of acute leukaemia is uncommon in our patients with sickle cell disease more so the patients have high morbidity and mortality due to the sickling process. Acute leukemia is a malignant clonal disorder of haemopoietic precursor cells resulting in accumulation of immature blood cells in the bone marrow and blood. The objective of the case series was to highlight the challenges of diagnosis and management of SCD patients with acute leukaemia, the importance of peripheral blood film review and propound a possible risk factor.MethodsRecords of 58 patients diagnosed and managed for acute leukaemia over a 7 year period at the University College Hospital, Ibadan were reviewed. The diagnosis of acute leukaemia was based on clinical features in addition to peripheral and bone marrow smears findings. Microsoft excel version 2013 was used for statistical analysis.ResultsFive (8.6%) of the patients with acute leukaemia also had sickle cell disease: 3 males and 2 females were described. Recurrent fever and anaemia were the most consistent presenting features in the patients. All the patients were not on any routine medications meant for SCD patients and had poor history of clinic attendance prior to the diagnosis of acute leukaemia. The diagnosis of acute leukaemia was not made until the patients were seen by a haematologist. The principal tool of diagnosis in all the patients was peripheral blood film review. Two patients were discharged against medical advice. The treatment period ranged between one month and one year in the remaining three patients.ConclusionSCD patients are not exempted from developing acute leukaemias and the diagnoses of the two conditions overwhelms the social and economic support of patients and care givers. The study also underscores the relevance of high level of suspicion and prompt review of peripheral blood film of SCD patients particularly when patients present with unremitting symptoms associated with anaemia and fever.     

A brief review of the pathophysiology, associated pain, and psychosocial issues in sickle cell disease

Sickle cell disease (SCD) is the most common genetic disorder of the blood. The disease produces significantly abnormal hemoglobin (Hgb) molecules in red blood cells (RBCs). The sickling of RBCs occurs when partially or totally deoxygenated Hgb molecules distort their normal disk shape, producing stiff, sticky, sickle-shaped cells that obstruct small blood vessels and produce vasoocclusion as well as the disruption of oxygen to body tissues. Because tissue damage can occur at multiple foci, patients with SCD are at risk for other medical complications including, but not limited to, delayed growth and sexual maturation; acute and chronic pulmonary dysfunction; stroke; aseptic necrosis of the hip, shoulders, or both; sickle cell retinopathy; dermal ulcers; and severe chronic pain. The chronicity of the illness combined with frequent hospitalizations for pain and other medical management can contribute significantly to impaired psychosocial functioning, altered intra- and interpersonal relationships, and reduced quality of life. Unlike previous qualitative reviews of SCD, this article describes the relevant clinical and research data on the relation between psychosocial functioning and SCD in adult and child populations. The authors discuss the significant role of psychosocial issues in the trajectory and management of the disease and conclude that understanding the pathophysiology of SCD without thoroughly understanding the equally important psychosocial influences is misunderstanding SCD.     

Neurocognitive development of young children with sickle cell disease through three years of age

OBJECTIVE: To determine (1) the neurocognitive development of children with sickle cell disease (SCD) from 6 months through 36 months of age, (2) the independent and combined contributions of biomedical risk and parenting risk to child neurocognitive functioning, and (3) the independent and combined contributions of biomedical risk, parent cognitive processes, and family functioning to parent adjustment. METHOD: The study sample included 89 African American children and their parents served through the Duke University-University of North Carolina Comprehensive Sickle Cell Center. Measures of cognitive and psychomotor development were obtained at 6, 12, 24, and 36 months of age, and parents completed self-report measures of the cognitive processes of daily stress and attributional style, psychological adjustment, and family functioning. RESULTS: There was no significant decrease in psychomotor functioning (PDI) over time but cognitive functioning (MDI) declined, with a significant decrease occurring between the 12- and 24-month assessment points. At 24 months, poorer cognitive functioning was associated with parenting risk, in terms of a learned-helplessness attributional style, and biomedical risk, in terms of HbSS phenotype. Levels of psychological distress within the clinical range were reported by 24% of the parents, and poorer parent adjustment was associated with high levels of daily stress, less knowledge about child development, lower expectations of efficacy, and HbSC phenotype. CONCLUSIONS: The findings indicate that young children with SCD are at risk for neurocognitive impairment and provide support for the initiation of early intervention studies to promote neurocognitive development.