Significance of fever in Jamaican patients with homozygous sickle cell disease

OBJECTIVE: To investigate the cause and outcome of high fever in Jamaican children with homozygous sickle cell disease. DESIGN: Retrospective review of febrile episodes in a three year period (1 September 1993 to 31 August 1996). SETTING: Sickle Cell Clinic, an outpatient clinic in Kingston run by the Medical Research Council Laboratories (Jamaica). PATIENTS: Patients with homozygous sickle cell disease under 17 years of age presenting with an anxillary temperature o 39.0§c (102.4§F). MAIN OUTCOME MEASURES: Diagnosis, death. RESULTS: There were 165 event in 144 patients (66 (45.8 percent) boys) with a median age of 6.1 years. Bacteraemia was found in 10 (6.1 percent) events (three Streptococcus pneumoniae, two Haemophilus influenzae type b, two Salmonella sp, one Escherichia coli, one Enterobactor sp, and one Acinetobacter sp), and urinary tract infections in four (2.4 percent). All cultures of cerebrospinal fluid were sterile. Acute chest syndrome occured in 36 (21.8 percent) events. A painful crisis was associated with 45 (27.3 percent) events and was the only pathology identified in 20 events (12.1 percent). Hospital admission was necessary in 66 cases including all those with bacteraemia and 31 with acute chest syndrome. There were two deaths: a 5 year old boy with septic shock associated with H influenzae septicaemia, and a 3 year old boy with the acute chest syndrome. CONCLUSIONS: Painful crisis and acute chest syndrome were the most common complications associated with high fever, but other important associated features included bacteraemia and urinary tract infection. Enteric Gram negative organisms accounted for 50 percent of positive blood cultures. (AU)

Psychological distress among younger siblings of patients with homozygous sickle cell disease in the Jamaican cohort study

The presence of a chronically ill family member may adversely affect the psychological health of siblings. This study used the General Health Questionnaire and the Modified Social Adjustment Scale to assess psychological distress in 20 younger siblings (4 AA, 16 AS genotypes), aged 16-19 years, of patients with homozygous sickle cell (SS) disease. The results were compared with those previously obtained in the 20 older siblings with SS disease and in 89 controls with a normal haemoglobin (AA) genotype. High levels of psychological distress occurred among all three groups. Greater psychological distress and poorer social adjustment occurred among siblings compared to AA controls but these differences disappeared after adjusting for the reduced age of sibings. The two measures were similar in SS patients and AA controls. The level of psychological distress among siblings of SS patients did not differ from that in SS patients or AA controls.(Au)

Gallstones in sickle cell disease: observations from the Jamaican Cohort study

The prevalence, incidence, risk factors, clinical associations, and morbidity of gallstones were studied in 311 patients with homozygous sickle cell disease and 167 patients with sickle cell-hemoglobin C disease in a cohort study from birth. Gallstones developed in 96 patients with homozygous sickle cell disease and 18 patients with sickle cell-hemoglobin C disease; specific symptoms necessitating cholecystectomy occurred in only 7 patients with homozygous sickle cell disease.(AU)

Postsplenectomy course in homozygous sickle cell disease

OBJECTIVE: To determine whether children with homozygous sickle cell (SS) disease and splenectomy are at greater risk of death, overwhelming septicemia, or other complications. METHODS: A total of 130 patients with SS treated by splenectomy (46 recurrent acute splenic sequestration, 84 chronic hypersplenism) over a 22.5-year period at the Sickle Cell Clinic of the University Hospital of the West Indies, Kingston, Jamaica, were compared with a control group matched for sex, age, and duration of follow-up in a retrospective review. Deaths and bacteremias were examined over the whole study period. Painful crises, acute chest syndromes, and febrile episodes were compared in the 90 patients completing 5 years of postsplenectomy follow-up. FINDINGS: Mortality and bacteremic episodes did not differ between the splenectomy and control groups. Painful crises were more common in the splenectomy group than in the control group (P = .01) but did not differ between splenectomy indications. Acute chest syndrome was more common in the splenectomy group than in the control group (P < .01) and was more common in the acute splenic sequestration group than in the hypersplenism group (P = .01). Febrile events did not differ between the groups or between the indications for splenectomy. CONCLUSION: Splenectomy does not increase the risk of death or bacteremic illness in patients with SS disease and, if otherwise indicated, should not be deferred for these reasons (Au)

Activated protein C resistance in homozygous sickle cell disease

The activated protein C resistance (APC-R) ratios in 50 patients with steady state homozygous sickle cell (SS) disease and 59 healthy AA controls was measured. There was a significant reduction in median APC-R ratio in sickle cell disease compared to controls. This reduction in APC-R ratio was not explained by (1) the presence of the factor V Leiden, found in only one of 165 patients with SS disease including those tested for APC-R, or (2) the presence of lupus anticoagulants. However, the raised levels of factor VIIIC in SS patients in this study may be contributing to the increased resistance to APC, which in turn may contribute to the vaso-occlusive complication of SS disease.(AU)

Benign clinical course in homozygous sickle cell disease: a search for predictors

AIMS: (1) To estimate the proportion of subjects with homozygous sickle cell disease who have a benign clinical course, and (2) to assess factors that may be predictive of benign disease. MATERIAL: Subjects (n = 280) were participants in a longitudinal cohort study of sickle cell disease. They were classified as benign or control based on clinical history from birth to age 13 years old. Associations with growth, hematology, and an index of social status were investigated. RESULTS: Benign disease occurred in 43 (15 percent) patients. Neither growth nor social status were related to benign disease. There were only two statistically independent association: alpha thalassemia status and average steady state fetal hemoglobin (HbF). Patients with a normal complement of alpha globin genes were 2.2 (1.0, 4.9) times more likely to have frequent painful crises, dactylitis, and bone necrosis. The odds of having benign disease were 1.09 (1.02, 1.17) times higher for each unit increase in HbF, and 44 percent of subjects with HbF in the top decile (HbF > 13.8 percent) of the distribution had benign disease. There was no evidence for a threshold effect of high HbF on benign disease. CONCLUSION: A benign clinical course of sickle cell disease may occur in Jamaica and is associated with a normal alpha globin gene complement, and high levels of HbF. Ability to predict benign disease at birth is limited.(AU)

Psychiatric complications of homozygous sickle cell disease among young adults in the Jamaican Cohort Study

BACKGROUND: This study aimed to determine the prevalence of psychiatric disorder in young adults with homzygous sickle cell (SS) disease and in contols with normal haemoglobin, and to examine factors associated with psychiatric disorder. METHOD: The study design was cross-sectional. Subjects were aged 18-20 years: 63 with SS disease and 89 controls. The Psychiatric Assessment Schedule was used to determine psychiatric disorder at index of definition level 5. RESULTS: Psychiatric disorder was identified in 18 (29 percent) SS disease patient and in 22 (25 percent) control. In SS patients, psychiatric disorder was not related to illness severity but was associated with leaving school early, difficulties in social adjustment, impaired cognitive function and having previous psychiatric difficulties. Male SS patients with psychiatric disorder all had low body mass index (BMI < 17.60). In controls, psychiatric disorder was associated with female gender, unemployment and difficulties in social adjustment. CONCLUSION: The prevalence of psychiatric disorder was similar in patients and controls, although associated factors tended to be different. The association with low BMI in SS men merits further study.(AU)

Statistical analysis of data for three British ethnic groups from a new STR multiplex

Data have been collected from 602 Caucasians, 190 Afro-Caribbeans and 257 Asians of Indo/Pakistani descent who have been profiled using a new six locus short tandem repeat (STR) multiplex. The data have been analysed by conventional significance testing methods: the exact test, homozygosity, and conventional goodness of fit to Hardy-Weinberg proportions. Frequency tables are given and the expected performance in British forensic casework is discussed.(AU)

Biliary sludge in sickle cell disease

Biliary sludge was observed in the gallbladder in 17 of 429 patients in a cohort study of sickle cell disease. Discrete gallstones later developed in 12 patients, but no stones developed in five patients; one patient with biliary sludge had no change in his condition for 5 years. None of the patients with biliary sludge had any symptoms referable to the biliary tract, and cholecystectomy has not been performed. The Jamaican experience suggests that biliary sludge may be treated conservatively, similar to our approach to asymptomatic gallstone. (AU)

Penicillin resistant streptococcus pneumoniae in a Jamaican patient with homozygous sickle cell disease

Penicillin prophylaxis against infection by Streptococcus pneumoniae is now routine in young children with homozygous sickle-cell (SS) disease and the emergence of penicillin-resistant strains is a serious clinical concern. The first death associated with such resistance in a Jamaican child with SS disease is reported (AU)

Factors affecting prepubertal growth in homozygous sickle cell disease

OBJECTIVE: To investigate the role of hematological indices, socioeconomic status, and morbidity in prepubertal growth in homozygous sickle cell (SS) disease from birth to 9 years at the sickle cell clinic of the University Hospital of the West Indies, Kingston, Jamaica. RESULTS: Height increment between 3 and 9 years correlated positively with total haemoglobin at age 7 years in boys but not girls. Attained height and weight at 7 years correlated positively with haemoglobin and fetal haemoglobin in boys but not girls. Only the correlation between haemoglobin and weight showed a significant gender difference. Partial correlation analysis suggested that the effect of haemoglobin was accounted for by the effect of fetal haemoglobin and further analysis indicated that height correlated with F reticulocyte count (a measure of fetal haemoglobin production) in both sexes but not with the ratio of F cells to F reticulocytes (a measure of F cell enrichment). Growth was not significantly related to mean red cell volume, proportional reticulocyte count, alpha thalassaemia, socioeconomic status, or morbidity. CONCLUSION: A high concentration of fetal haemoglobin in boys with SS disease is associated with greater linear growth. It is postulated that in boys, low concentrations of fetal haemoglobin increase haemolysis and hence metabolic requirements for erythropoiesis, putting them at greater risk of poor growth. Differences in the relationship to haemotoloy and growth between boys and girls with SS disease dictate that future analyses of growth take gender into account (AU).x

Improved survival in homozygous sickle cell disease: lessons from a cohort study

OBJECTIVE: To examine whether simple interventions in a sickle cell clinic improve survival in sickle cell disease. DESIGN: Survival curve analysis and hazard ratios in a cohort study followed from birth. SETTING: MRC Laboratories (Jamaica) at the University of the West Indies, and Victoria Jubilee Hospital, Kingston, Jamaica. SUBJECTS: 315 patients with homozygous sickle cell disease detected during the screening of 100,000 consecutive non-operative deliveries between June 1973 and December 1981 at the main government maternity hospital, Kingston, Jamaica. INTERVENTIONS: Prophylactic penicillin to prevent pneumococcal septicaemia, parental education in early diagnosis of acute splenic sequestration, close monitoring in sickle cell clinic. MAIN OUTCOME MEASURES: Survival. RESULTS: Survival appeared to improve, the log rank test for trend comparing the first, second, and last third of the study reaching borderline significance (P = 0.05). Combined deaths from acute splenic sequestration and pneumococcal septicaemia-meningitis declined significantly (test for trend, P = 0.02). CONCLUSION: Early diagnosis and simple prophylactic measures significantly reduce deaths associated with homozygous sickle cell disease (AU)

Factors associated with lowered intelligence in homozygous sickle cell disease

The intelligence quotient (IQ) of 60 patients with homozygous sickle cell (SS) disease and 60 age and sex matched controls with a normal haemoglobin (AA) genotype aged 15-18 years, followed up in a cohort study from birth, was assessed by the Wechsler intelligence scales for children and adults. IQ appeared to be normally distributed in both genotypes but mean values in SS disease were 5.6 points (95 percent confidence interval (CI) 1.0 to 10.2) lower than in AA controls (p=0.016). THe difference occurred in both verbal (5.5 points, p=0.017) and performance (5.0 points, p=0.044) subscales of the IQ defect in SS disease was associated with a significantly lower attention factor score (p=0.005) but not with other factor scores. The genotype difference in IQ was not accounted for by differences in parental occupational level, school absenteeism, or school drop out, or reported activity level. In SS disease, IQ was not related to mean steady state haemoglobin, or mean cell haemoglobin concentration, or clinical severity as judged by the frequency of painful crises, hospital admission, or sick visits. IQ, at age 15-18 years, correlated with the patients' height at all ages from 1 to 10 years (partial correlations increasing from 0.14 (p=0.15) at age 1 to 0.27 (p=0.004) at age 10). Adjusting for height reduced the mean genotype difference in IQ to 5.5 (95 percent CI 0.6 to 10.3) points at age 1 and 10 2.6 points (95 percent CI 0.6 to 10.3) points at age 10. Prepubertal height therefore accounted for much of the genotype difference in IQ. It is speculated that early factors, possibly nutritional, contribute to both impaired growth and mental development in sickle cell disease(AU)

Glomerulonephritis after human parvovirus infection in homozygous sickle-cell disease

Glomerulonephritis with proteinuria of sufficient degree to manifest the nephrotic syndrome followed aplastic crises induced by human parvovirus (B19) in seven patients with homozygous sickle-cell disease, within 7 days in five patients and 6-7 weeks in two. Segmental proliferative glomerulonephritis was found in all four patients who underwent acute renal biopsies and focal segmental glomerulosclerosis was found in the fifth patient who had a biopsy 4 months later. One patient recovered completely, one died in chronic renal failure after 3 months, and the others had impaired creatinine clearance, four with continuing proteinuria (AU)

Testosterone deficiency and extreme retardation of puberty in homozygous sickle-cell disease

Homozygous sickle-cell (SS) disease is associated with retardation of physical and sexual development but most Jamaican children commence their adolescent growth spurt before 16 years of age. Analysis of growth from children in the Jamaican Cohort Study noted extreme growth retardation , defined as an absence of the adolescent growth spurt and pre-pubertal sexual development (Tanner stage 1 or 2) at age 16 years, in 8/52 (15 percent) SS boys. These and two boys from the general sickle-cell clinic with a similar growth pattern provided a study group of 10 boys who were investigated for a possible endocrine explanation for their extreme retardation of physical maturation. A sub-optimal testosterone response (<10 nmol/l) to human chorionic gonadotrophin and an exaggerated gonadotrophin hormone releasing hormone was consistent with poor testicular function in 5 boys. Retardation of adolescent growth and development is common in boys wit SS disease but, when extreme, requires early investigation to identify potentially correctable mechanisms (AU)

Daily variability in resting levels of cardiovascular variable in normal subjects and those with homozygous sickle cell disease

Measurements were made of cardiovascular variables and oral temperature in 16 male subjects with homozygous sickle cell disease (SS) and in 17 matched controls (AA) at 10.00 a.m, 1.00 p.m and 4.00 p.m. All subjects were in a rested state throughout. At 10.00 a.m. mean arterial pressure was lower, while heart rate, total forearm blood flow and cutaneous red cell flux in the forearm were higher in SS than AA. Vascular resistance in total forearm and forearm skin, calculated by dividing arterial pressure by blood flow or red cell flux, were lower in SS but hand cutaneous red cell flux and vascular resistance were not significantly different in SS and AA. In both SS and AA, there were parallel increase over the three sessions, in mean arterial pressure (by approximately 12 and 10 percent respectively) forearm vascular resistance (by approximately 17 and 27 percent) and hand cutaneous vascular resistance and hand cutaneous resistance (by approximately 2240 and 350 percent) whereas forearm blood flow and hand cutaneous red cell flux fell. By contrast, forearm cutaneous resistance showed no change during the day in SS, but increased progressively in AA (by approximately 75 percent). These results indicate that, during the day, there is progressive vasconstriction in forearm muscle and hand skin in SS and AA and also in forearm skin of AA that contributes to a progressive rise in the resting level of mean arterial pressure. We suggest this daily variability should be considered in studies of cardiovascular function: within a given study they should be performed at the same time of day.(AU)

Sensorineural hearing loss in sickle cell anaemia: a United Kingdom study

Sensorineural hearing loss (SNHL) has been a well-documented complication of sickle cell disease in the literature from West Africa, West Indies, United Stated of America and the Middle East. We present a study of 52 patients with homozygous sickle cell disease and 36 control patients with haemoglobin genotype AA, matched for age and sex. Seven patients with sickle cell disease (13.5 per cent) were found to have sensorineural hearing loss i.e. > 20 dB at two or more frequencies, while all the patients in the control group had normal hearing (p < 0.05). Our study shows the incidence of SNHL in the UK to be similar to that reported in the USA and much lower than that found in malaria endemic areas of the tropics. We highlight the factors which we consider reponsible for these differences and suggest that the crucial period in the development of SNHL in sickle cell patients should be encouraged to have regular hearing assessment (AU)

Influence of alpha thalassaemia on the retinopathy of homozygous sickle cell disease

Homozygous alpha+ thalassaemia (alpha-/alpha-) ameliorates some of the clinical manifestations of homozygous sickle cell (SS) disease but its effect on retinal complications remains unknown. This has been assessed by visual examination and flourescein angiography in 39 subjects with SS disease and homozygous alpha+ thalassaemia and in 39 age/sex matched controls with SS disease but with a normal alpha genotype (alpha alpha/alpha alpha). The results indicate that homozygous alpha+ thalassaemia reduces the extent of peripheral retinal vessel closure but has no apparent effect on the frequency of proliferative sickle retinopathy (AU)

Resting metabolic rate in homozygous sickle cell disease

The resting metabolic rate in 20 patients with homozygous sickle cell (SS) disease was 19 percent higher than in 20 age-and sex-matched control subjects with a normal hemoglobin genotype (AA). The difference was not accounted for by differences in lean body mass. It is postulated that this increased energy expenditure reflects the energy expenditure of erythropoietic hyperplasia and leads to a marginal nutritional state that may contribute to the abnormal growth in SS disease. (AU)