HbSS Genotype Research Articles

Radiographic changes of the jaws in HbSS and HbSC genotypes of sickle cell disease

This study used panoramic radiographs to evaluate the presence of radiographic changes in the jaws of a population who had sickle cell disease (SCD). The authors compared the frequency of findings between subjects with and without SCD. Panoramic radiographs of 71 subjects with SCD (36 with HbSS and 35 with HbSC) and 52 healthy controls (HbAA) were evaluated for the presence of the following radiographic alterations: radiopaque areas, increased spacing of bony trabeculae, horizontal arrangement of bony trabeculae, and absence of mandibular canal corticalization. The control group had a significantly smaller number of all the radiographic features evaluated. Differences were not statistically significant between the groups with HbSS and HbSC, except for more trabecular spacing in the molar region in the HbSS genotype, suggesting a possible correlation between radiographic findings and disease presentation.

Higher Rates of Hemolysis Are Not Associated with Albuminuria in Jamaicans with Sickle Cell Disease

BackgroundAlbuminuria is a marker of glomerular damage in Sickle Cell Disease (SCD). In this study, we sought to determine the possible predictors of albuminuria in the two more prevalent genotypes of SCD among the Jamaica Sickle Cell Cohort Study participants.MethodsAn age-matched cohort of 122 patients with HbSS or HbSC genotypes had measurements of their morning urine albumin concentration, blood pressure, body mass index, haematology and certain biochemistry parameters done. Associations of albuminuria with possible predictors including hematological parameters, reticulocyte counts, aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) levels were examined using multiple regression models.ResultsA total of 122 participants were recruited (mean age 28.6 years ±2.5 years; 85 HbSS, 37 HbSC). 25.9% with HbSS and 10.8% with HbSC disease had microalbuminuria (urine albumin/creatinine ratio = 30–300 mg/g of creatinine) whereas 16.5% of HbSS and 2.7% of HbSC disease had macroalbuminuria (urine albumin/creatinine ratio>300 mg/g of creatinine). Mean arterial pressure, hemoglobin levels, serum creatinine, reticulocyte counts and white blood cell counts were statistically significant predictors of albuminuria in HbSS, whereas white blood cell counts and serum creatinine predicted albuminuria in HbSC disease. Both markers of chronic hemolysis, i.e. AST and LDH levels, showed no associations with albuminuria in either genotype.ConclusionsRenal disease, as evidenced by excretion of increased amounts of albumin in urine due to a glomerulopathy, is a common end-organ complication in SCD. It is shown to be more severe in those with HbSS disease than in HbSC disease. Rising blood pressure, lower hemoglobin levels and higher white blood cell counts are hints to the clinician of impending renal disease, whereas higher rates of hemolysis do not appear to play a role in this complication of SCD.

The 844ins68 cystathionine beta-synthase and C677T MTHFR gene polymorphism and the vaso-occlusive event risk in sickle cell disease

IntroductionSickle cell disease (SCD) is an inflammatory condition with an increase in the adhesion of sickled erythrocytes, and it is a potential cause of vaso-occlusive episodes, an event related to clinical manifestations, morbidity and mortality. The cystathionine beta-synthase enzyme gene (CBS) and the methylenetetrahydrofolate reductase enzyme gene (MTHFR) are risk factors for thromboembolic disorders. This study evaluated the frequency of the 844ins68 CBS and C677T MTHFR gene polymorphisms and their possibility to be risk factors for vaso-occlusive crises.Material and methodsIn total 91 blood samples from SCD patients were studied by PCR-RFLP and PCR-allele-specific, for the SCD genotype confirmation and polymorphism identification.ResultsThe presence of clinical manifestations related to vaso-occlusive crises were more frequent among patients with the Hb SS genotype (p = 0.007). The CBS enzyme gene was three times more frequent (p = 0.011) among patients with vaso-occlusive complications. The MTHFR gene mutation frequency showed no increased risk for vaso-occlusive crises in SCD patients (p = 0.193). The interaction between the two polymorphisms was evaluated in 12.08% of the SCD patients and doubled the vaso-occlusive disease risk (relative risk: 2.16).ConclusionsWe conclude that the presence of 844ins68 CBS and C677T MTHFR gene polymorphism was a risk factor for vaso-occlusive episodes in the SCD patients evaluated.

Endothelium-dependent and endothelium-independent vasodilatation of the cutaneous circulation in sickle cell disease

Whilst there is evidence of endothelial dysfunction in sickle cell disease (SCD), whether this affects regulation in the microcirculation is not known. We studied 19 patients with SCD, eight with sickle cell-haemoglobin C (HbSC), 11 with homozygous sickle cell (HbSS) disease and 11 matched control subjects with normal haemoglobin genotype (HbAA). Vasodilator responses were evoked by iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) in finger and forearm, cutaneous red cell flux (RCF) being measured by laser Doppler fluximetry. Increases in RCF evoked in the finger by ACh were not different between SCD and HbAA subjects (P = 0·789), but were smaller in patients with HbSS than HbSC (P < 0·05). By contrast, increases in RCF evoked in forearm by ACh were greater in SCD than HbAA subjects (P < 0·05) and similar in patients with HbSC and HbSS. Increases in RCF evoked by SNP did not differ between patients with SCD and HbAA subjects in finger or forearm. Our results indicate that endothelium-dependent cutaneous vasodilatation is augmented in forearm of patients with SCD relative to HbAA subjects, but impaired in the finger of SCD patients with the more severe HbSS genotype. Thus, endothelial dysfunction associated with SCD is not accompanied by generalised impairment in endothelium-dependent dilatation, but with more localised impairment that includes the fingers of patients with HbSS.

Serum B12 Levels In Children with Sickle Cell Disease Are Lower Than In Healthy Control Subjects

AbstractAbstract 1647Clinical B12 (cobalamin) deficiency occurs in sickle cell disease (SCD) but it is uncommon (NEJM 2003;348:2204). Several publications report lower serum B12 concentrations in SCD subjects than in controls (Acta Haematol 1984;71:299; J Intern Med 1995;237:551; J Nat Med Assoc 2006;98:352). However, other studies do not show these differences (Am J Hematol 2004;76:114; South Med J 2004;97:149; J Am Coll Nutr 2000;19:608). Serum transcobalamin concentrations are high in SCD (Scand J Haematol 1983;30:135; Acat Haematol 1989;81:117) so that one would expect higher than normal B12 levels in these patients. We measured serum B12 concentrations in 467 children and adolescents with SCD and in 69 control subjects matched for age, sex, and ethnicity. All subjects were enrolled in the PUSH protocol, a multicenter study for determining the prevalence and significance of pulmonary hypertension in children with SCD. The median serum B12 concentration in SCD was lower than in controls (960 vs. 1094 pg/ml, p=0.003). No patient had a serum B12 value lower than 227 pg/ml (3 SD below the mean of control subjects) and sickle genotype did not affect B12 concentration. Univariate analysis in children with the Hb SS genotype (N=343) showed that age, body mass index, serum creatinine (all three p=0.0001), and red cell MCV (p=0.025) were each inversely correlated with B12 levels, and this suggested the possibility that as children grow, their B12 requirements increase. In SS children higher leukocyte counts, serum AST, and serum ALT were all associated with higher B12 levels (p=0.005, p=0.0001, and 0.011, respectively), while blood Hb concentration, a-thalassemia status, Hb F %, platelet count, and hemolytic parameters were unrelated to serum B12. The median B12 level in SS children (941 pg/ml) remained significantly lower than that of controls even after adjustment for age and WBC. Children with Hb SS who were taking hydroxyurea had significantly lower median B12 levels (845 pg/ml, N=141) than SS children not on this drug (992 pg/ml, N=200 p=0.027) (Figure) but after adjustment for age and WBC this difference was no longer significant (p=0.5).These results suggest that (a) children with SCD have lower, though still normal, serum B12 concentrations than healthy subjects, (b) this difference is not explained by SCD leukocytosis so that it could represent increased B12 requirements, and (c) hydroxyurea treatment reduces B12 levels even further probably as a result of its lowering effect on leukocyte count. However, because hydroxyurea was not given in a randomized manner, we cannot exclude the confounding effect of age on B12 level in hydroxurea treated subjects. Since we and others (Acat Haematol 1989;81:117) show that in SCD serum B12 decreases with age, as is the case also in non-SCD individuals (Am J Clin Nutr 1997;66:741), it would seem prudent to monitor cobalamin levels in SCD adults, particularly in older subjects and in those taking hydroxyurea. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Heart Function Disorders In Sickle Cell Disease

AbstractAbstract 4815Abstract Background:Sickle cell disease (SCD) is a hereditary anemia characterized by chronic hemolytic anemia and vaso-occlusive episodes, associated with a high susceptibility for infections and damage to all vital organs. Cardiologic effects of SCD are dilatation and hypertrophy of the left ventricle and pulmonary hypertension. The prevalence of these cardiac complications in children with SCD living in the Netherlands is unknown. The role of hemolysis in this process is still unclear. Therefore, the objectives of this study are: 1) to evaluate the prevalence of cardiac abnormalities in children with SCD living in the Netherlands, 2) to analyse the association between cardiac abnormalities and the severity of anemia and hemolysis. Methods:Cross-sectional study, including 92 children with SCD (genotype HBSS, HBSC or HBS-beta 0) treated at the Emma Children's Hospital AMC. None of the children had cardiac abnormalities unrelated to SCD. Echocardiograms and electrocardiograms were performed in a stable state. All cardiac values were corrected for BSA. Echocardiographic values 20% above or under the average of an age matched control group were considered abnormal. Laboratory hematological parameters were obtained within one year of the cardiac imaging. All statistical analyses were performed with SPSS 18 software, using Pearson correlations and T-tests. Forced-entry multivariate regression analysis was conducted with hematological parameters, age and SCD genotype as independent variables and cardiologic parameters as dependent variables. Results:The study group had a mean age of 13 years (SD 5,5) and contained 49 boys (53,3%). All children had a normal shortening fraction. Almost half of the children (39%) had a dilated left ventricular internal diameter in diastole and systole. Dilatation was inversely correlated with the Hb level. When analysed with multivariate analysis, both Hb and bilirubin were independently associated with left ventricular dilatation, suggesting that hemolysis deteriorates cardiac structure by a mechanism separate from the effect of anemia. There was no association between the left ventricular dilatation and age. Conclusion:Pediatric sickle cell patients have significant dilatation of the left ventricle, an abnormality that is significantly and independently associated with the severity of anemia and bilirubin levels, but in spite retain a normal shortening fraction. Disclosures:No relevant conflicts of interest to declare.

Polysomnographic Characteristics of a Referred Sample of Children with Sickle Cell Disease

To describe polysomnographic parameters and their clinical correlates in a referred sample of children with sickle cell disease (SCD). This was a retrospective medical record review of 55 consecutive children aged 2-18 years with SCD (hemoglobin [Hb] SS and Hb SC genotypes) undergoing polysomnography for evaluation of sleep disordered breathing. Polysomnography values were compared between SCD genotypes, 4 age groups, and adenotonsillectomy status using descriptive and nonparametric statistics. Obstructive sleep apnea (OSA) was diagnosed in 38/55 (69%) children. Polysomnographic parameters differed significantly between Hb SS and Hb SC genotypes only on arterial oxyhemoglobin saturation (SpO2; 95.2 +/- 3.8 vs. 98.0 +/- 0.8, respectively, p < 0.01) and percent of sleep time below SpO2 90% (T90; 8.0 +/- 22.0 vs. 0.01 +/- 0.02, respectively, p < 0.05). Increasing age was associated with decreasing SpO2 (rho = -0.282, p < 0.05), obstructive apnea-hypopnea index (OAHI; rho = -0.364, p < 0.01), total arousal index (rho -0.272, p < 0.05) and respiratory arousal index (rho = -0.349, p < 0.01). Periodic limb movements in sleep (PLM) averaged 4.7 +/- 8.8/h, with a PLM index > 5/h in 5/17 children without OSA. Post- adenotonsillectomy, 8/10 children had OSA, but compared to untreated OSA-positive children they had a lower mean OAHI (4.4 +/- 5.5 vs. 8.9 +/- 12.5) and a lower T90 (1.6 +/- 4.2 vs. 9.2 +/- 24.9). Both OSA and PLMs were common in children with SCD. Children with Hb SS experienced more severe nocturnal oxygen desaturation than did those with Hb SC. Post-adenotonsillectomy, most children had OSA, although they experienced fewer obstructive respiratory events and less severe nocturnal oxygen desaturation than did untreated OSA-positive children.

Ocular Manifestations of Sickle Cell Disease at the Korlebu Hospital, Accra, Ghana

To determine the magnitude and pattern of ocular manifestations in sickle cell disease at Korle-bu Hospital, Accra, Ghana. Hospital-based cross-sectional study including all patients with sickle cell disease reporting for routine follow-up at the Sickle Cell Clinic at Korle-bu Hospital, Accra, Ghana. A total of 201 patients with sickle cell disease (67 male and 134 female) were enrolled, comprising 114 subjects with genotype HbSS, aged 6-58 years, mean 19.26 (SD 11.70), and 87 with genotype HbSC, aged 6-65 years, mean 31.4 (SD 16.76). Visual impairment was found in 5.6% of eyes examined. Causes were cataract, proliferative sickle retinopathy (PSR), optic atrophy, phthisis bulbi, and central retinal artery occlusion. Common anterior segment signs of sickle cell disease, which were more common in HbSC patients, were tortuous corkscrew conjunctival vessels, iris atrophy, and cataract. Eyes with iris atrophy or depigmentation were 1.8 times more at risk of PSR than eyes without. Overall, PSR was found in 12.9% of subjects examined (3.5% of HbSS, 25.3% of HbSC; 15.9% of males and 11.2% of females). The prevalence of proliferative sickle retinopathy increased with age and increased systemic severity of sickle cell disease; sex did not have an influence. There is a high prevalence of ocular morbidity in sickle cell disease patients at Korle-bu Hospital. Prevalence increased with age, systemic severity of sickle cell disease, and HbSC genotype.

Ocular manifestations of sickle cell disease

Sickle cell disease (SCD) is the most common genetic disease worldwide. The increase in life expectancy of SCD patients in recent years has led to the emergence of more complications of the disease, e.g. ocular, which in the past were uncommon. This review describes current knowledge of the ocular manifestations of patients with SCD. SCD can affect virtually every vascular bed in the eye and can cause blindness in the advanced stages. The most significant ocular changes are those which occur in the fundus, which can be grouped into proliferative sickle retinopathy, and non-proliferative retinal changes based on the presence of vascular proliferation. This distinction is important because the formation of new vessels is the single most important precursor of potentially blinding complications. Although various systemic complications of SCD are known to be more common in patients with the Hb SS genotype, visual impairment secondary to proliferative sickle retinopathy is more common in patients with the Hb SC genotype. There is also an increase with age in the incidence and prevalence rates of all ocular complications of SCD. It is therefore recommended that all patients with SCD undergo periodic ophthalmological screening from the age of 10 years.

Spectrum of musculo-skeletal disorders in sickle cell disease in Lagos, Nigeria.

BackgroundSickle cell anemia (SCA) is a common genetic disease in Nigeria. Past studies from West Africa focused on isolated aspects of its medical and surgical presentations. To the best of our knowledge, the musculo-skeletal presentations amongst Nigerians with SCA have not been documented in a single all encompassing study. This work aims to prospectively document the musculo-skeletal disease burden among SCA patients.MethodsIn a prospective study of 318 consecutive patients with genotype-confirmed SCA at the Lagos University Teaching Hospital (LUTH), the musculo-skeletal pathologies, anatomic sites, grade of disease, age at presentation and management outcome were recorded over a one-year period. Data obtained were analyzed using Epi-Info software version 6.0. Data are presented as frequencies (%) and mean values (SD) as appropriate.ResultsThe HbSS genotype occurred in 296 (93.0%), while 22 (7.0%) were HbSC. 100 (31.4%) patients with average presenting haemoglobin concentration of 8.2 g/100 ml in the study group, presented with 131 musculo-skeletal pathologies in 118 anatomic sites. Osteomyelitis 31 (31%) and septic arthritis 19 (19%) were most commonly observed in children less than 10 years. Skin ulcers and avascular necrosis (AVN) occurred predominantly in the older age groups, with frequencies of 13 (13.0%) and 26 (26.0%) respectively. 20 (71.5%) of diagnosed cases of AVN presented with radiological grade 4 disease. The lower limbs were involved in 84 (71.1%) of sites affected. Lesions involving the spine were rare 11 (0.9%). Multiple presentations occurred in 89 (28.0%) of patients; 62 (69.7%) of which were children below 10 years.ConclusionsMusculo-skeletal complications are common features of sickle cell anaemia seen in 31.4%. Infectious aetiologies predominate with long bones and joints of lower limbs more commonly affected by osteomyelitis and septic arthritis. Healthcare providers managing SCA should be aware of the potential morbidity and mortality of these conditions to ensure early diagnosis and adequate management.

Mortality and Causes of Death in Children with Sickle Cell Disease in the Netherlands.

Abstract 1519Poster Board I-542 IntroductionDespite the increasing incidence of sickle cell disease (SCD) in the Netherlands, mortality among this patient group has never been investigated. Studies on mortality in patients with SCD from the USA demonstrated that survival at the age of 20 years has improved from 79% for those born before 1975 to 89% in patients born after 1975. A recent study in the USA (2004) reflects the benefits of modern comprehensive care for SCD patients as survival increased to 94% by 18 years of age.The aim of this study was to collect information on the mortality rate and causes of death of children with SCD living in the Netherlands that were born before nationwide neonatal screening was implemented in 2007. This information is essential to provide a baseline for monitoring the effect of health care interventions, such as the introduction of nationwide neonatal screening. Causes of death may provide insight in areas where further improvement in the healthcare for SCD patients should be implemented. Patients and MethodsAll patients that were diagnosed with sickle cell disease (HbSS, HBSC, HbS-beta0, HbS-beta+) before the age of 18 years at the laboratory of the Academic Medical Center (AMC) in Amsterdam in 1985-2006 were included in the study. The AMC is one of the two large comprehensive care centers in the Netherlands, providing care to 30-40% of all Dutch SCD patients. Patients were followed from the time point of diagnosis onwards. Vital status at the end of study was determined by the last hospital visit or personal contact between January 2007 and March 2008. The causes of death were derived from hospital records. Survival estimates were obtained using the Kaplan-Meier estimator. ResultsIn this time period we identified 298 pediatric patients with SCD. Homozygous sickle cell disease (HbSS) was present in 189 (63%) patients. The total time of follow-up was 2621 patient years. Twenty four patients (8%) were lost to follow up. The median age of the patients at the end of the observation period was 14.5 years (IQR 8.7-21.0 years). Twelve patients had died and all deaths were SCD related. Stroke (3 patients; 25%) and sepsis/meningitis (3 patients; 25%) were the most common causes of death. Four children (33%) died under 3 years of age. In two of them, death coincided or occurred shortly after the diagnosis of SCD. Three patients (25%) were between 3-18 years and 5 patients (42%) were older than 18 years at the time of death.A similar proportion of patients with the HbSS and HbSC genotype died (respectively 4.2% (95% CI: 1.9-7.9%) and 4.2% (95% CI: 1.0-10.8%)). The overall mortality rate was 0.46 deaths (95% CI: 0.25-0.77) per 100 patient years. The estimated survival rate of children with SCD at the age of three years was 93% (95% CI: 87-100%). At the age of 18 the survival was 91% (95% CI: 84 -99%). DiscussionThe fact that a similar proportion of patients with the HbSS and HbSC genotype died is striking, as HbSC generally has a milder phenotype than HbSS. In the absence of a neonatal screening program, early death from severe infection may have contributed to a relatively high mortality in HbSC patients. Although the estimated survival at the age of 18 years is comparable to recent findings in a neonatally screened cohort from the USA, the mortality rate of 0.46 deaths per 100 patient years is high in comparison to the mortality rate of 0.13 per 100 patient years in an East London cohort of SCD patients. This may partly be explained by a younger age of this East London cohort (median 7.8 years). However, the benefits of a longer standing neonatal screening program within the UK is likely to contribute to the low mortality rate in the East London cohort as well.Conclusions: In children with SCD living in the Netherlands, born before nationwide neonatal screening was implemented in 2007, 91% survives until the age of 18. Infection and stroke are the most common causes of death. Further study of children with SCD born after 2007, when neonatal screening was implemented, will elucidate whether neonatal screening for SCD has improved survival in these patients. DisclosuresNo relevant conflicts of interest to declare.

Glutathione S-transferase activity of erythrocyte genotypes HbAA, HbAS and HbSS in male volunteers administered with fansidar and quinine

In vivo investigations were carried out to ascertain the comparative levels of erythrocyte GST activity between non-malarious and malarious male subjects of HbAA, HbAS and HbSS erythrocyte genotypes, administered with fansidar and quinine. The incubation of human erythrocytes with 1-chloro-2,4-dinitrobenzene (CDNB) resulted in almost quantitative conjugation of glutathione (GSH) to form S-(2,4-dinitrophenyl) glutathione. Determination of GST activity was carried out at 0, 3, 6 and 18 h, after two antimalarial drugs (Fansidar and quinine) were adminis-tered to the volunteers. The control values of non-malarious and malarious individuals ranged between (3.27 to 12.50 iu/gHb) and (2.75 to 12.21 -iu/gHb) respectively. Erythrocyte GST activity was significantly (p < 0.05) lower in P. falciparum infected red cells compared to normal ones, except parasitized male HbSS erythrocytes. Generally, the pattern of in vivo erythrocyte GST activity in the presence of the 2 antimalarial drugs showed 2 phase profile. The first stage showed decreasing levels of relative GST activity within approximate time range of 6 h after the drugs were administered to the volunteers. The second phase showed recovery of erythrocyte GST activity (6 - 18 h approx.) from the inhibitory effects of the drugs. Key words: Glutathione S-transferase (GST) activity, erythrocytes, fansidar, quinine, 1-chloro-2, 4-dinitrobenzene (CDNB).

Sickle Cell Disease: Ratio of Blood Flow Velocity of Intracranial to Extracranial Cerebral Arteries—Initial Experience

To establish reference values of the ratios of flow velocity in the middle cerebral artery (V(MCA)) and the terminal portion of the internal carotid artery (V(tICA)) to flow velocity in the extracranial portion of internal carotid artery (V(ICA)) in children with sickle cell disease (SCD). Institutional ethics committee approval and parental informed consent were obtained for this prospective HIPAA-compliant study. Sixty-eight children (38 female; mean age, 7.7 years +/- 3.3; range, 2-14 years) with HbSS genotype, without neurologic deficits and no history of stroke, were enrolled. Final study population comprised 56 (mean age 8.0 +/- 3.3 years, 26 females) children who underwent magnetic resonance (MR) angiography, which excluded intracranial arterial narrowing, transcranial color-coded duplex ultrasonography (US), and carotid US to determine V(MCA)/V(ICA) and V(tICA)/V(ICA) ratios from angle-corrected and uncorrected velocities. Tolerance interval estimates were used to calculate reference ranges and linear regression was used to quantify associations of Doppler parameters with age adjusted for hemoglobin and hematocrit. Reference ranges in centimeters per second for mean angle-corrected V(MCA) on the left and right sides were 62-198 and 69-153; those for V(tICA) were 30-196 and 36-175; and those for V(ICA) were 18-116 and 15-95, respectively. Reference ranges for mean angle-corrected V(MCA)/V(ICA) ratio on the left and right sides were 1.2-4.0 and 0.4-3.4 and those for V(tICA)/V(IC)(A) ratio were 0.5-2.9 and 0.5-2.7, respectively. V(MCA), V(tICA), and V(tICA)/V(ICA) ratio were not age dependent, contrary to V(ICA) and V(MCA)/V(ICA) ratio, after controlling for hematocrit and hemoglobin. The study provides reference limits for V(MCA), V(tICA), V(ICA), and velocity ratios obtained from children with SCD.

Evaluation of Antioxidant Levels and Trace Element Status in Nigerian Sickle Cell Disease Patients with Plasmodium Parasitaemia

Homozygous sickle cell disease (genotype HbSS) confers a certain degree of protection to human (especially Africans) Plasmodium falciparum malaria, yet the precise mechanism remains unknown. Recent observations suggest that the mechanism might also involve immune and non-immune components. In this study, the plasma levels of trace elements (Mg, Fe, Zn, Mn, Cu, Cr, Cd and Se) and antioxidants (urea, albumin and total antioxidants) were determined in Nigerians with sickle cell disease with (HbSS+M), or without (HbSS-M) Plasmodium parasitaemia, haemoglobin AA with Plasmodium parasitaemia (HbAA+M) compared with those having haemoglobin AA without Plasmodium parasitaemia (HbAA-M) using spectrophotometric method. The mean level of urea was significantly higher while the total antioxidants (TAS), Mg, Fe, Zn, Mn, Cu, Cr, Cd, Se and albumin were not significantly different in HbAA+M subjects when compared with HbAA-M subjects. In HbSS-M subjects, the levels of Fe, Zn, Mn and TAS were significantly lower while the level of urea was significantly higher when compared with HbSS+M subjects. There were no significant differences in the values of Mg, Cu, Cd, Se and albumin in HbSS-M subjects when compared with HbAA-M. In HbSS+M subjects, significantly lower levels of Fe, Zn, Mn, Cu, Cr, Cd, Se, total antioxidants, but significantly higher level of urea were observed when compared with the HbAA-M subjects. The result of this study revealed an aggravating effect of Plasmodium parasitaemia on deranged levels of trace elements in Nigerians with sickle cell disease.

Distribution of haemoglobin genotypes and anaemic status of HIV positive pregnant women in Enugu: a hospital based study

This present 4 – year comparative study investigated the distribution pattern of Haemoglobin genotypes and anaemic status of HIV positive pregnant women in Enugu. Haemoglobin variants(HbAA, HbAS, HbSS) in pregnant women attending antenatal clinics at the study site were determined by electrophoreisis. HIV screening tests were done using the Quick test kits. Packed Cell Volume (PCV) was estimated by using standard procedures. Results showed a prevalence rate of 83.3% was obtained for HbAA HIV+ pregnant women as against a 70.1% for HIV- pregnant women; HbAS rates were 16.7% for HIV+ pregnant women and 29.9% for HIV- pregnant women. For the non- pregnant women (control), the rates were 78.63% for HbAA and 21.4% for HbAS. No HbSS genotype was observed in the HIV+ pregnant women and HIV- pregnant women and the control respectively. The HIV seroprevalence rate of 3.67 +- 0.40%(SEM) was obtained for this study. The PCVs of the HIV+ pregnant women with HbAA and HbAS (1999 – 2002) fell into levels indicative of anaemia when compared with those of HIV- pregnant women and the control. Increased awareness, compulsory pre-marital sickling and HIV tests could be the possible reason for the low HIV seroprevalence and the absence of HbSS observed in this population. Nigerian Journal of Health and Biomedical Sciences Vol. 7 (1) 2008 pp. 27-30

The pattern of the frequency of hbsag, hbeag, anti-hcv and anti-hbe in patients with haemoglobin genotype HbSS and HbSC in a rural community.

Sixty HbSS sickle cell anaemic patients aged 17.45 ±10.1years (Female=30, Male=30) and sixty HbSC sickle cell disease patients aged 20.6±11.0years(Female=30,Male=30) were recruited for the investigation. Haemoglobin genotype of each of the patient was determined by electrophoresis. HepatitisB‘s' antigen, HBeAg,anti-HBe, and anti-HCV in patients' plasma were determined by Enzyme Immunoassay. The frequencies of HBsAg, anti-HBe, HBeAg +HBsAg, HBsAg + antiHBe, in HbSS(6.7% , 20%,13.3%, and 20% respectively) were higher than those of HbSC( 5% ,8.3%, 5% , and 3.3% respectively). The frequency of anti-HCV + anti-HBe in HbSC was higher compared with that of HbSS patients ( 3.3% Vs 0%).The frequency of HBeAg in female HbSS and HbSC patients was higher than their male counterparts.( HbSS:16.7%Vs 10%;HbSC:6.7% Vs 3.3%).Higher frequency of HBsAg was found in HbSS male patients than the females (26.7% Vs 13.3%).The frequency of anti-HBe in HbSS male patients and HbSC female patients was higher than those of HbSS female patients and HbSC male patients respectively( HbSS:10% Vs 3.3%; HbSC: 10% Vs 6.7%).The frequency of HBeAg+ HBsAg obtained in HbSS male patients and HbSC female patients was higher than the results obtained from HbSS female patients and HbSC male patients (HbSS: 16.7% Vs 10%; HbSC:6.7% Vs 3.3%).The frequency of HBsAg + anti-HBe in HbSS female patients was higher than in HbSS male patients.(23.3% Vs 16.7%).None of the patients plasma was found to contain both HBeAg + anti-HBe. This research work has therefore been used to examine the pattern of HBeAg, HBsAg, anti-HCV, and anti-HBe in the plasma of patients with haemoglobin genotype HbSS and HbSC in rural community. Keywords : Pattern, Frequency, HepatitisB, Hepatitis C, Antibody, Surface (‘s') and Envelope (‘e') antigens. African Journal of Clinical and Experimental Microbiology Vol. 9 (2) 2008 pp. 82-87

Predictors of In-Hospital Mortality and Charges in Sickle Cell Disease: Results from the California Discharge Databases 1998–2005.

Most studies of survival in sickle cell disease (SCD) include only patients followed at referral centers. We used the public set of the California Patient Discharge Databases (1998–2005) to compare in-hospital mortality and charges by patient characteristics. We included discharges with any diagnostic code for SCD (282.41–2, 282.60–69). We used the Charlson index (adapted for administrative data) to adjust for comorbid conditions. Hospital charges were adjusted to 1998 levels. Statistical methods included ANOVA, Wilcoxon rank-sum, and multivariate linear and logistic regression. We identified 57,887 admissions for SCD and 376 in-hospital deaths (0.65%) from 1998–2005. The mean age of death was 40 years (95% CI 38–42) for sickle cell anemia (HbSS) and 48.3 years (95% CI 44.1–52.5, p<.0005) for all other SCD. Median length of stay was 4 days (IQR 2–7 days) and charges were $10,027 (IQR 5547–18,302) for HbSS and 4 days (IQR 2–6 days) and $8045 (IQR 4375–16,253) for all other SCD (p<.0001). Women with SCD were older at the time of death (43.6 years) than men (41.4 years, p=.29) and age of death increased from 40.6 years in 1998–2000 to 44.2 in 2004–2005 (p=.17) but these differences were not significant. Mortality was increased with a Charlson Index of 1 or 2, older age, private insurance, a diagnosis of HbSS, and transfusion during the admission (Table 1). Women had a lower odds of death than men (OR 0.7, p<.05). Average annual charges for hospitalization in patients with SCD, adjusted to 1998 values, were $117,000,000 and decreased $1,960,000/year (−4.1%, p<.0001) for children and increased $1,150,000/year (1.4% p<0.05) for adults. Adjusted charges for all children were stable and increased 1.5% per year for adults. Charges per admission were $3167 higher for adults than children, $5608 higher per comorbid diagnosis, $6506 higher in transfused patients, and $3595 higher with a diagnosis of crisis (p<.0001 for all). Compared to MediCal, charges were $1186 higher for Medicare (p<.05), $2651 lower for other government insurance (p<.0001), and $3521 lower for self-pay (p<.05). Government (77%) and private insurance (21%) paid for most admissions. We identified a greatly increased risk of in-hospital morality with comorbid diagnoses and older age and moderately increased risk with private insurance, HbSS genotype, and transfusion during the admission. The increased risk with private insurance was surprising, as higher socioeconomic status is often associated with better health outcomes. This may reflect more stringent requirements for admission or financial barriers to outpatient and preventive services for SCD. Total charges decreased dramatically in children, possibly reflecting increased use of hydroxyurea for frequent pain and chronic transfusions for primary stroke prevention.Table 1:Odds Ratio for In-Hospital Death Based on Multivariate Logistic RegressionVariableOdds Ratio (95% CI)P-ValueCharlson Index=13.3 (2.4–4.6)<.0001Charlson Index=212.9 (9.3–18)<.0001Age (per year)1.04 (1.03–1.05)<.0001Private Insurance vs. MediCal1.6 (1.2–2.2)<.0005Medicare vs. MediCal0.9 (0.7–1.3)NSOther SCD vs. HbSS0.7 (0.5–0.9)<.0005Transfusion1.6 (1.2–2.0)<.0001NS indicates not significant

Musculoskeletal Complications And General Health Status Of Individuals With Sickle Cell Disease

Sickle cell disease is a chronic disease that is associated with high degree of morbidity and mortality. The objective of this study was to find the relationship between musculoskeletal complications and general health status of patients with sickle cell disorders. &#x0D; &#x0D; The HSQ 2.0 questionnaire, (a general health survey questionnaire), was used to assess the subjects’ health status while a separate questionnaire was used to compile data on complications. Descriptive and inferential statistic of Spearman’s correlation was used to find relationship between complications and health status. Level of significance was set at 0.05 alpha.&#x0D; &#x0D; Seventy-two subjects with sickle cell disorder participated in the study. Fifty-six (77.8%) were of genotype Hb SS. Most of the subjects, 51 (70.8%) normally experienced back pain, 22 (30.5%) had chest pain while only 2.8% had visual problem. Generally, subjects scored low on all health status sub-scales except the mental health sub-scale where the mean score was near 60% (59.84 ± 17.41%). The lowest mean score (47.99 ± 24.03%) was obtained on role limitation due to physical health sub-scale. There were significant correlations between complications and health status.&#x0D; &#x0D; It was concluded that the health of individuals with sickle cell disease is compromised on all the eight domains of health status and that painful complications affect their social and physical functioning and impose limitation on them. It was also concluded that the more the number of body parts with pain the lower the health status become.&#x0D; &#x0D; KEYWORDS: Musculoskeletal complications; Health status; Sickle cell disease.

Mean Platelet Volume in Children with Sickle Cell Disease on Chronic Transfusion Therapy.

The symptoms in sickle cell disease are related to ischemic/vaso-occlusive episodes involving the bones, spleen, brain and lungs. One of the possible mechanisms for vaso-occlusion is platelet activation and increased platelet reactivity which is demonstrated by increased platelet volume resulting in an elevated platelet distribution width. We hypothesized that chronic transfusion therapy given to patients with recurrent severe ischemic episodes and/or stroke may lower mean platelet volume (MPV) in addition to decreasing hemoglobin S. We performed a retrospective chart analysis of all patients with sickle cell disease who were on a chronic transfusion regimen at Schneider Children's Hospital between January 1995 and March 2005. Out of 60 eligible patients, only 42 were eligible for this study. The remaining patients were excluded for less than 3 transfusions in total or incomplete records. The data retrieved included age and sex of the patient, type of sickle cell disease, indication for chronic transfusion therapy, duration of transfusions and blood count variables during the three phases, i.e. prior to, during and after transfusion therapy. The variables included hemoglobin, mean cellular volume, platelet count, reticulocyte count and MPV for each patient with a minimum of one value in each phase. As many values were recorded based on the availability in the records, with at least an interval of 3 months between each blood count and at least 3 months apart from a transfusion.Results: Sixty-four percent were males and 95% had HbSS genotype. The major indication for transfusion therapy (85%) was stroke. Mean values of each variable and their ranges were compared across the 3 periods using the Kruskal Wallis test. Although the platelet count decreased significantly during transfusions compared to pre-transfusion period, the mean value of MPV did not differ across the 3 periods with a range between 5.9 and 11.3 in all the 3 periods. Furthermore, using the Anacova method proposed by Bland and Altman, there was an overall significant negative correlation between MPV and platelet count, while no correlation at all was present between MPV, reticulocyte count and hemoglobin in any of the 3 periods. Our findings suggest that multiple transfusions do not alter platelet size or volume, which indirectly may indicate that there is no change in platelet function or activity in these patients on chronic transfusion therapy. The changes in MPV values seen in this study are real, as they follow the natural thrombokinetics by maintaining a negative correlation with the platelet count during all 3 periods.

Serum magnesium, phosphate and calcium in Nigerian children with sickle cell disease

Biochemical abnormalities have been associated with sickle cell disease. Studies on phosphorus and magnesium in sickle cell disease have been conflicting. There is paucity of information on the role of these ions in the pathogenesis and management of sickle cell disease. This study was set out to determine the serum levels of magnesium, phosphorus and calcium in Nigerian children with sickle cell disease. A case-control study carried out on children with HbSS genotype (cases) and age-matched controls with HbAA. Serum magnesium, calcium, phosphorus and albumin were measured using colorimetric methods. Eighty-six subjects and forty-five controls were studied. The mean serum magnesium was 0.99mmol/L (0.02) and 0.98mmol/L (0.02) in the cases and controls respectively. The difference was not significant. Mean serum calcium was significantly lower in the cases [2.1mmol/L (0.3)] compared with the controls [2.3mmol/ L (0.15)]; p<0.01. Serum phosphorus was significantly higher in the cases than in the controls [2.2mmol/L (0.7) versus (1.5mmol/L (0.6); p<0.001]. There was no statistical difference in the albumin binding of calcium in both groups. A positive correlation existed between serum phosphorus and magnesium and also between serum calcium and magnesium in the cases group but no correlation between these parameters and age was found. Children with sickle cell anaemia in this study had normo-magnesaemia, hyperphosphataemia and hypocalcaemia. Further studies on changes in intracellular concentrations of these ions in children with sickle cell disease are required. Such findings could be useful in designing better management in individuals with this abnormality.