Pain Burden in the CASiRe International Cohort of Sickle Cell Patients: United States and Ghana.

OBJECTIVES: Sickle Cell Disease (SCD) is a genetic blood disorder affecting over 1 million people globally. The aim of this analysis is to explore the pain burden of patients with SCD in two countries: the United States and Ghana. METHODS: The Consortium for the Advancement of Sickle Cell Research (CASiRe) was created to better understand the clinical severity of patients with SCD worldwide. Data regarding gender, SCD genotype, prior medical diagnoses, and validated pain burden measures were analyzed from the CASiRe database. The Sickle Cell Pain Burden Interview (SCPBI) was used to assess pain burden, the impact of pain on physical, emotional, and social function. RESULTS: Most subjects identified as Black/African American (n = 298, 97.0%). Patient ages ranged from 6 to 73 years. 35.9% resided in the United States, 64.1% resided in Ghana, 40.9% were men, and 58.7% were women. The mean SCPBI score for US SCD patients was 6.53(±5.89) vs 4.04(±5.10) for Ghanaian patients, P <0.001. Pain burden was higher in US men vs Ghanaian men (6.74(±5.68) vs 3.54(±4.46), P = .003) and in US women vs Ghanaian women (6.37 ± 6.06 vs 4.44(±5.54), P = .032). Pain burden was higher in US patients than Ghanaian patients for both the Hb SC/SBeta+ genotype (5.40(±5.29) vs 2.82(±4.86), P = .054) and Hb SS/SBeta0 genotype (6.79(±6.01) vs 4.49(±5.13), P = .003). Pain burden was significantly higher in SCD patients with comorbid conditions independent of geographic origin including stroke, cholecystectomy, gallstones, depression, and headache. DISCUSSION: US patients with SCD have a higher pain burden than Ghanaian patients. Further studies should investigate underlying contributors to pain burden in these populations and further explore the etiology of geographic differences in pain.

Age of first pain crisis and associated complications in the CASiRe international sickle cell disease cohort.

Pain is a hallmark of Sickle Cell Disease (SCD) affecting patients throughout their life; the first pain crisis may occur at any age and is often the first presentation of the disease. Universal newborn screening identifies children with SCD at birth, significantly improving morbidity and mortality. Without early screening, diagnosis is generally made after disease manifestations appear. The Consortium for the Advancement of Sickle Cell Research (CASiRe) is an international collaborative group evaluating the clinical severity of subjects with SCD using a validated questionnaire and medical chart review, standardized across 4 countries (United States, United Kingdom, Italy and Ghana). We investigated the age of first pain crisis in 555 sickle cell subjects, 344 adults and 211 children. Median age of the first crisis in the whole group was 4 years old, 5 years old among adults and 2 years old among children. Patients from the United States generally reported the first crisis earlier than Ghanaians. Experiencing the first pain crisis early in life correlated with the genotype and disease severity. Early recognition of the first pain crisis could be useful to guide counseling and management of the disease.

Global geographic differences in healthcare utilization for sickle cell disease pain crises in the CASiRe cohort.

BACKGROUND: Sickle cell disease (SCD) is characterized by frequent, unpredictable pain episodes and other vaso-occlusive crises (VOCs) leading to significant healthcare utilization. VOC frequency is often an endpoint in clinical trials investigating novel therapies for this devastating disease. PROCEDURE: The Consortium for the Advancement of Sickle Cell Research (CASiRe) is an international collaboration investigating clinical severity in SCD using a validated questionnaire and medical chart review standardized across four countries (United States, United Kingdom, Italy and Ghana). RESULTS: This study, focused on pain crisis incidence and healthcare utilization, included 868 patients, equally represented according to age and gender. HgbSS was the most common genotype. Patients from Ghana used the Emergency Room/Day Hospital for pain more frequently (annualized mean 2.01) than patients from other regions (annualized mean 1.56 U.S.; 1.09 U.K.; 0.02 Italy), while U.K. patients were hospitalized for pain more often (annualized mean: U.K. 2.98) than patients in other regions (annualized mean 1.98 U.S.; 1.18 Ghana; Italy 0.54). Italy's hospitalization rate for pain (annualized mean: 0.57) was nearly 20 times greater than its emergency room/day hospital only visits for pain (annualized mean: 0.03). When categorized by genotype and age, similar results were seen. CONCLUSIONS: Geographic differences in pain crisis frequency and healthcare utilization may correlate with variable organization of healthcare systems among countries and should be considered regarding trial design, endpoints, and analysis of results when investigating novel agents for clinical benefit.

Diagnosis patterns of sickle cell disease in Ghana: a secondary analysis.

BACKGROUND: Despite having the highest prevalence of sickle cell disease (SCD) in the world, no country in Sub-Saharan Africa has a universal screening program for the disease. We sought to capture the diagnosis patterns of SCD (age at SCD diagnosis, method of SCD diagnosis, and age of first pain crisis) in Accra, Ghana. METHODS: We administered an in-person, voluntary survey to parents of offspring with SCD between 2009 and 2013 in Accra as a part of a larger study and conducted a secondary data analysis to determine diagnosis patterns. This was conducted at a single site: a large academic medical center in the region. Univariate analyses were performed on diagnosis patterns; bivariate analyses were conducted to determine whether patterns differed by participant's age (children: those < 18 years old whose parents completed a survey about them, compared to adults: those > = 18 years old whose parents completed a survey about them), or their disease severity based on SCD genotype. Pearson's chi-squared were calculated. RESULTS: Data was collected on 354 unique participants from parents. Few were diagnosed via SCD testing in the newborn period. Only 44% were diagnosed with SCD by age four; 46% had experienced a pain crisis by the same age. Most (66%) were diagnosed during pain crisis, either in acute (49%) or primary care (17%) settings. Children were diagnosed with SCD at an earlier age (74% by four years old); among the adults, parents reflected that 30% were diagnosed by four years old (p < 0.001). Half with severe forms of SCD were diagnosed by age four, compared to 31% with mild forms of the disease (p = 0.009). CONCLUSIONS: The lack of a robust newborn screening program for SCD in Accra, Ghana, leaves children at risk for disease complications and death. People in our sample were diagnosed with SCD in the acute care setting, and in their toddler or school-age years or thereafter, meaning they are likely being excluded from important preventive care. Understanding current SCD diagnosis patterns in the region can inform efforts to improve the timeliness of SCD diagnosis, and improve the mortality and morbidity caused by the disease in this high prevalence population.

A study of the geographic distribution and associated risk factors of leg ulcers within an international cohort of sickle cell disease patients: the CASiRe group analysis.

Vasculopathy is a hallmark of sickle cell disease ultimately resulting in chronic end organ damage. Leg ulcer is one of its sequelae, occurring in ~ 5-10% of adult sickle cell patients. The majority of leg ulcer publications to date have emanated from single center cohort studies. As such, there are limited studies on the geographic distribution of leg ulcers and associated risk factors worldwide. The Consortium for the Advancement of Sickle Cell Research (CASiRe) was formed to improve the understanding of the different phenotypes of sickle cell disease patients living in different geographic locations around the world (USA, UK, Italy, Ghana). This cross-sectional cohort sub-study of 659 sickle cell patients aimed to determine the geographic distribution and risk factors associated with leg ulcers. The prevalence of leg ulcers was 10.3% and was associated with older age, SS genotype, male gender, and Ghanaian origin. In fact, the highest prevalence (18.6%) was observed in Ghana. Albuminuria, proteinuria, increased markers of hemolysis (lower hemoglobin, higher total bilirubin), lower oxygen saturation, and lower body mass index were also associated with leg ulceration. Overall, our study identified a predominance of leg ulcers within male hemoglobin SS patients living in sub-Saharan Africa with renal dysfunction and increased hemolysis.

Correlation of lipid peroxidation and nitric oxide metabolites, trace elements, and antioxidant enzymes in patients with sickle cell disease.

BACKGROUND: Lipid peroxidation plays a very important role in sickle cell pathophysiology. The formation of malondialdehyde (MDA) in patients with sickle cell disease (SCD) may lead to endothelial dysfunction. Nitric oxide (NO) is a known vasodilator which plays a role in endothelial function. The current study determined the association between MDA and NO metabolites (NOx), trace elements, and antioxidant enzymes (SOD and CAT) in patients with SCD. The ratio of MDA/NOx was also determined as an index of oxidative stress in the study groups. METHODS: This was a cross-sectional study involving 90 patients with SCD and 50 "healthy" controls. Blood samples (n = 140) were collected from the study groups. The plasma, sera, and red cells were kept at -20°C for biochemical analyses. Hemoglobin (Hb) and NOx levels were determined in the plasma using Labsystem Multiskan MS and Griess reagent system, respectively. Super oxide dismutase (SOD) and catalase (CAT) levels were determined in the red cells using assay kits from Cayman chemicals. Lipid peroxidation biomarker MDA was determined in the sera using the TBARS assay. Levels of iron (Fe), copper (Cu), and zinc (Zn) were also determined in the sera using Variant 240FS. MDA and NOx ratio was computed for the study groups and compared. RESULTS: Levels of Hb, NOx, SOD, CAT, and Zn were significantly lower in the patients with SCD (P < .001). MDA, Fe, and MDA/ NOx ratio were, however, significantly higher in the patients with SCD (P < .001). There was no significant correlation between MDA and NOx, SOD, CAT, Fe, and Zn in the study groups. MDA, however, correlated positively and significantly with Cu in the HbSS patients with vaso-occlusive crises (VOC). Gender did not affect the levels of oxidative stress markers. CONCLUSIONS: Findings from this study suggest a link between lipid peroxidation and Cu in HbSS patients with VOC. Increased MDA/NOx ratio may contribute to sickle cell pathophysiology by promoting oxidative stress.

Total Serum Magnesium Levels and Calcium-To-Magnesium Ratio in Sickle Cell Disease.

Background and objectives: Imbalance of calcium/magnesium ratio could lead to clinical complications in sickle cell disease (SCD). Low levels of magnesium have been associated with sickling, increased polymerization and vaso-occlusion (VOC) in sickle cell due to cell dehydration. The K-Cl cotransport plays a very important role in sickle cell dehydration and is inhibited by significantly increasing levels of magnesium. The study evaluated total serum magnesium levels and computed calcium/magnesium ratio in SCD patients and "healthy" controls. Materials and methods: The study was a case-control cross-sectional one, involving 120 SCD patients (79 Haemoglobin SS (HbSS)and 41 Haemoglobin SC (HbSC)) at the steady state and 48 "healthy" controls. Sera were prepared from whole blood samples (n = 168) and total magnesium and calcium measured using a Flame Atomic Absorption Spectrometer (Variant 240FS manufactured by VARIAN Australia Pty Ltd., Melbourne, VIC, Australia). Calcium/magnesium ratios were calculated in patients and the controls. Results: The prevalence of hypomagnesemia and hypocalcaemia among the SCD patients was observed to be 39.17% and 52.50% respectively, higher than the controls (4.17% and 22.92%, for hypomagnesemia and hypocalcaemia, respectively). Level of magnesium was significantly lower in the SCD patients compared to their healthy counterparts (p = 0.002). The magnesium level was further reduced in the HbSS patients but not significantly different from the HbSC patients (p = 0.584). calcium/magnesium ratio was significantly higher in the SCD patients (p = 0.031). Although calcium/magnesium ratio was higher in the HbSC patients compared to those with the HbSS genotype, the difference was not significant (p = 0.101). Conclusion: The study shows that magnesium homeostasis are altered in SCD patients, and their levels are lower in HbSS patients. Although calcium/magnesium ratio is significantly higher in SCD patients compared with controls, there is no significant difference between patients with HbSS and HbSC genotypes. Magnesium supplementation may be required in sickle cell patients.

Serum Iron Levels and Copper-to-Zinc Ratio in Sickle Cell Disease.

Background and Objectives: Altered copper and zinc homeostasis may influence the antioxidant defense system and consequently lead to oxidative stress and associated complications in sickle cell disease (SCD) patients. Iron levels have been reported to increase in sickle cell patients due to frequent blood transfusion, chronic intravenous haemolysis and increased absorption of iron from the gastrointestinal tract. These elevated levels of iron may also lead to extensive oxidative damage. The current study evaluated serum levels of iron, copper and zinc in SCD patients and "healthy" controls. Materials and Methods: The study was a cross-sectional one, comprising 90 SCD patients with Haemoglobin SS and Haemoglobin SC genotypes and 50 HbAA "healthy" controls. Serum levels of iron, copper and zinc were measured using a Flame Atomic Absorption Spectrometer (Variant 240FS manufactured by VARIAN Australia Pty Ltd, VIC, Australia). Copper and zinc ratios were calculated and analyzed. Results: Serum levels of iron and copper were significantly elevated in the SCD patients, compared to their "healthy" counterparts (p < 0.001). These levels were further increased in patients with haemoglobin SS in vaso-occlusive crises (HbSS VOCs). Serum zinc levels were, however, significantly lower in the SCD patients, particularly during vaso-occlusion. The copper-to-zinc ratio was also found to be significantly higher in the SCD patients. Conclusion: Elevated copper-to-zinc ratio may be a biomarker of sickle cell oxidative stress and associated complications. The ratio may also be informative for the management of sickle cell oxidative burden. The significantly lower levels of zinc in the SCD patients may warrant zinc supplementation.

Maternal serum angiopoietins levels in pre-eclampsia and pregnancy outcomes.

Background and Aims: Although the understanding of pre-eclampsia (PE) has improved, there is still insufficient knowledge on the exact etiology and pathophysiological mechanisms. Dysregulation of angiogenic factors has emerged as a significant contributing factor. Among these factors, angiopoietins (Ang-1 and Ang-2) have gained considerable attention due to their crucial role in regulating vascular development and endothelial function. This study explored the maternal serum levels of angiopoietins and perinatal outcomes in PE. Methods: A case-control study involving women with PE (cases) and normotensive pregnancies (controls) was conducted at the Maternity unit of the Korle-Bu Teaching Hospital. Descriptive analysis was performed and the Mann-Whitney U test (two-sided) was used to compare maternal serum levels of angiopoietins between the cases and controls. Results: We included 188 participants comprising 94 cases (women with PE) and 94 controls (normotensive pregnancies) with an average maternal age of 29.76 ± 5.56 and 28.43 ± 5.57 years, respectively. Maternal serum levels of Ang-2 were significantly lower among the PE cases compared to the normotensive controls (1.25 [0.90, 2.15] vs. 2.14 [1.18, 5.73] ng/mL, p = 0.001) but no significant difference in Ang-1 levels (92.61 [80.92, 114.92] vs. 99.26 [81.76, 113.12] ng/mL, p = 0.429) was observed between the groups. The Ang-1/Ang-2 ratio was significantly elevated among women with PE compared to normotensive controls (74.47 [37.69, 110.59] vs. 45.98 [16.11, 88.22] ng/mL, p = 0.014). Also, women who delivered vaginally had significantly high maternal serum levels of Ang-1 compared to women who had cesarean section delivery (107.98 ± 27.79 vs. 89.02 ± 32.62 ng/mL). Conclusion: Maternal serum levels of Ang-2 but not Ang-1 were significantly depressed in women with PE compared to the pregnant normotensive controls. No significant associations were observed between Ang-1, Ang-2 levels, or the Ang-1/Ang-2 ratio and pregnancy outcomes such as preterm birth, birth weight, and severity of hypertension.

Associations between spirometric measures and exercise capacity in type 2 diabetes.

BACKGROUND: Physical exercise aids glycemic control and the prevention of diabetes-related complications. However, exercise beyond an individual's pulmonary functional capacity may be detrimental. To date, little is known about the relationship between pulmonary function and exercise capacity in people with type 2 diabetes (T2D). We investigated the relationship between pulmonary function and exercise capacity in T2D. METHODS: Spirometry and 6-min walk test (6MWT) were conducted for 263 systematically sampled adults with T2D without primary heart/lung disease. The primary measure of exercise capacity was the 6-min walk distance (6MWD); impaired exercise capacity was defined as 6MWD<400 m. Logistic regression analyses were used to assess the associations between spirometric measures and exercise capacity with adjustments for age, sex, height, body mass index, diabetes duration, glycated hemoglobin concentration, smoking, suboptimum blood pressure control, and total cholesterol concentration. RESULTS: Compared with individuals with normal spirometry, those with pulmonary restriction/obstruction had significantly lower 6MWD (404.67 m vs. 451.70),p < 0.001). The proportion of individuals with impaired exercise capacity was higher in individuals with impaired pulmonary function compared with those with normal pulmonary function (39.8% vs. 20.7%,p = 0.001). In the unadjusted models, decreasing Z-score FEV1 [odds ratio 1.40, 95% confidence interval (1.07-1.83),p = 0.013] and Z-score FVC [1.37 (1.06-1.76),0.016], but not Z-score FEV1/FVC ratio [1.00 (0.78-1.27),0.972] were significantly associated with impaired exercise capacity. In the fully adjusted model, the strength of association remained statistically significant for Z-score FEV1 [1.60 (1.06-2.41),0.025] but not Z-score FVC [1.48 (0.98-2.23),0.065]. CONCLUSIONS: Our study shows inverse associations between FEV1 and impaired exercise capacity in T2D, Future research could characterize optimal exercise levels based on a patient's FEV1.

Pain Frequency and Health Care Utilization Patterns in Women with Sickle Cell Disease Experiencing Menstruation-Associated Pain Crises.

Background: Pain crises in sickle cell disease (SCD) lead to high rates of health care utilization. Historically, women have reported higher pain burdens than men, with recent studies showing a temporal association between pain crisis and menstruation. However, health care utilization patterns of SCD women with menstruation-associated pain crises have not been reported. We studied the frequency, severity, and health care utilization of menstruation-associated pain crises in SCD women. Materials and Methods: A multinational, cross-sectional cohort study of the SCD phenotype was executed using a validated questionnaire and medical chart review from the Consortium for the Advancement of Sickle Cell Research (CASiRe) cohort. Total number of pain crises, emergency room/day hospital visits, and hospitalizations were collected from a subcohort of 178 SCD women within the past 6 months and previous year. Results: Thirty-nine percent of women reported menstruation-associated pain crises in their lifetime. These women were significantly more likely to be hospitalized compared with those who did not (mean 1.70 vs. 0.67, p = 0.0005). Women reporting menstruation-associated pain crises in the past 6 months also experienced increased hospitalizations compared with those who did not (mean 1.71 vs. 0.75, p = 0.0016). Forty percent of women reported at least four menstruation-associated pain crises in the past 6 months. Conclusions: Nearly 40% of SCD women have menstruation-associated pain crises. Menstruation-associated pain crises are associated with high pain burden and increased rates of hospitalization. Strategies are needed to address health care disparities within gynecologic care in SCD.

Hazardous emissions and concentrations of toxic metalloids and trace elements in charcoals from six commonly used tropical timbers for carbonization.

Carbonized wood is a biofuel from cellulose pyrolysis with frequent smoke and life-threatening carcinogenic emissions. Carbon monoxide (CO), particulate matter (PM2.5), metalloids and trace elements from charcoals from six commonly used tropical timbers for carbonization in Donkorkrom (Ghana) were assessed. During combustion, Anogeissus leiocarpa charcoal emitted the least CO (4.28 ± 1.08 ppm) and PM2.5 (3.83 ± 1.57 µg/m3), while particulate matter was greatest for Erythrophleum ivorense (28.05 ± 3.08 ppm) and Azadirachta indica (27.67 ± 4.17 µg/m3) charcoals. Erythrophleum ivorense charcoal produced much lead (16.90 ± 0.33 ppm), arsenic (1.97 ± 0.10 ppm) and mercury (0.58 ± 0.003 ppm) but the least chromium (0.11 ± 0.01 ppm) and zinc (2.85 ± 0.05 ppm). Nickel was greatest for A. indica charcoal (0.71 ± 0.01 ppm) and least for Vitellaria paradoxa (0.07 ± 0.004 ppm). Trace elements ranged from 342.01 ± 2.54 ppm (A. indica) to 978.47 ± 1.80 ppm (V. paradoxa) for potassium and 1.74 ± 0.02% (V. paradoxa) to 2.24 ± 0.10% (A. indica) for sulphur. Besides A. leiocarpa charcoal, which ranked safest during combustion, the high PM2.5 and CO emissions make the other biofuels hazardous indoors. Kitchens need air filters to absorb these emissions together with the use of improved cook stoves. These carcinogenic metalloids would necessitate that their ashes be properly discarded without human contact. Yet, the charcoals would be much suitable as soil amendment bio-char for plant growth quality improvement.

Association between pulmonary function and cardiac enzymes in sickle cell disease.

BACKGROUND: There is scarcity of data on association between lung function and cardiac markers in patients with sickle cell disease (SCD). Meanwhile, SCD affects multi-organs in any one population. There seem to be an association between reduced pulmonary function with cardiac dysfunction. The current study examined the association between pulomanry function with cardiac markers in patients with SCD. METHODOLOGY: This was a cross-sectional study with cases and controls. The cases (n=117) were made up of patients with SCD. The control subjects (n=58) were voluntary blood donors without SCD. The cellulose acetate electrophoresis was used to determine the genotypes of the study subjects. Blood samples were collected from all the study subjects for full blood count and measurement of cardiac enzymes. The cardiac enzymes measured were lactate dehydrogenase (LDH) and creatine kinase-myocardial band (CK-MB). Lung function test, using the vitalograph was done on all the study subjects. The Global Lung Initiative criteria were used to categorize lung disease as obstruction, restriction, mixed obstruction/restriction and normal. RESULTS: The prevalence of elevated CK-MB and LDH among the SCD patients was 76.92% and 9.40% respectively, higher than the non-SCD controls (51.72% and 0% for elevated CK-MB and LDH respectively). Of all the impaired lung function, lung restriction was prevalent in all the study groups (30.77% and 15.52% for SCD patients and non-SCD controls respectively). In the fully adjusted model, reduced FEV1 was associated with nearly 3.5-fold higher odds of elevated CK-MB (odds ratio 3.35, 95% CI 1.26-8.90, p-value 0.015) in individuals with SCD. CONCLUSION: Reduced FEV1 which reflects airflow impairments are associated with CK-MB elevations in patients with SCD, suggesting a possible damage to the cardiomyocytes.

Exercise-induced haemoglobin oxygen desaturation in patients with SCD.

BACKGROUND: Patients with sickle cell disease (SCD) may experience severe clinical complications when there is low tissue oxygenation due to the increased risk of the polymerization of haemoglobin S in deoxygenated environment. The predictors of oxygen desaturation after exercise is not clear in patients with SCD. The current study compared lung function and six-minute walk test (6MWT) between SCD patients with oxygen desaturation after exercise and those without oxygen desaturation. METHODOLOGY: A cross-sectional study was conducted among adults with SCD (with HbSS and HbSC genotypes) at a large tertiary hospital in Accra, Ghana. Lung function and exercise tolerance (using the 6MWT) were performed for all the study subjects (n=119). Venous blood was collected from all the study subjects for determination of some haemolytic markers. Oxygen saturation was assessed before and after the 6MWT for all the study subjects, and individuals who had oxygen desaturation of ≥3% after the 6MWT were considered as having exercise-induced haemoglobin oxygen desaturation (EIHOD). The lung function and 6MWT were compared between these two groups. Predictors of EIHOD were determined in both HbSC and HbSS patients. RESULTS: The prevalence of EIHOD in the HbSS and HbSC adults were 41% and 36.1% respectively. Haemoglobin, aspartate amino transaminase, indirect bilirubin, lactate dehydrogenase and six-minute walk distance did not differ in both HbSS and HbSC patients. Decreasing haemoglobin is a predictor of EIHOD in HbSC adults but not HbSS patients. Lung function abnormalities did not predict EIHOD in both HbSS and HbSC patients. CONCLUSION: The study demonstrates that SCD patients with EIHOD have similar degree of haemolysis and lung function when compared to those without EIHOD.

An Analysis of Racial and Ethnic Backgrounds Within the CASiRe International Cohort of Sickle Cell Disease Patients: Implications for Disease Phenotype and Clinical Research.

Millions are affected by sickle cell disease (SCD) worldwide with the greatest burden in sub-Saharan Africa. While its origin lies historically within the malaria belt, ongoing changes in migration patterns have shifted the burden of disease resulting in a global public health concern. We created the Consortium for the Advancement of Sickle Cell Research (CASiRe) to understand the different phenotypes of SCD across 4 countries (USA, UK, Italy, and Ghana). Here, we report the multi-generational ethnic and racial background of 877 SCD patients recruited in Ghana (n = 365, 41.6%), the USA (n = 254, 29%), Italy (n = 81, 9.2%), and the UK (n = 177, 20.2%). West Africa (including Benin Gulf) (N = 556, 63.4%) was the most common geographic region of origin, followed by North America (N = 184, 21%), Caribbean (N = 51, 5.8%), Europe (N = 27, 3.1%), Central Africa (N = 24, 2.7%), and West Africa (excluding Benin Gulf) (N = 21, 2.4%). SCD patients in Europe were primarily West African (73%), European (10%), Caribbean (8%), and Central African (8%). In the USA, patients were largely African American (71%), Caribbean (13%), or West African (10%). Most subjects identified themselves as Black or African American; the European cohort had the largest group of Caucasian SCD patients (8%), including 21% of the Italian patients. This is the first report of a comprehensive analysis of ethnicity within an international, transcontinental group of SCD patients. The diverse ethnic backgrounds observed in our cohort raises the possibility that genetic and environmental heterogeneity within each SCD population subgroup can affect the clinical phenotype and research outcomes.

Oxidative Profile of Patients with Sickle Cell Disease.

Oxidative stress plays a very significant role in the pathophysiology of sickle cell disease (SCD) and associated complications. Oxidative stress, which is often experienced by SCD patients as a result of continuous production of reactive oxygen species (ROS), may lead to endothelial dysfunction and acute inflammation. Antioxidant enzymes, such as superoxide dismutase (SOD) and catalase (CAT), often play a protective role. The current study aimed at determining the oxidative profile of persons with SCD at a tertiary hospital in Ghana. This was a case-control study involving 90 patients with SCD (34 HbSS patients at steady state, 30 HbSC at steady state, 15 HbSS with vaso-occlusive crisis, 11 HbSC with vaso-occlusive crisis), and 50 HbAA control group. Whole blood samples were collected from the study participants and analyzed for full blood counts. The blood samples were assayed for SOD and CAT as a measure of antioxidant defense, while lipid peroxidation was quantified as malondialdehyde (MDA). The results showed that the levels of SOD and CAT were significantly lower in SCD patients as compared to the control group. Patients with HbSS vaso-occlusive crisis had the lowest levels of SOD and CAT. The difference in SOD levels between HbSS at steady state and HbSC with vaso-occlusive crisis was, however, not significant (p = 0.228). The MDA level was significantly higher in SCD patients compared to the control group. This study concludes that the levels of various antioxidant enzymes (erythrocyte SOD and erythrocyte CAT) and oxidative marker (MDA) and are altered in SCD patients.

Serum Potassium, Sodium, and Chloride Levels in Sickle Cell Disease Patients and Healthy Controls: A Case-Control Study at Korle-Bu Teaching Hospital, Accra.

The activity of Na+-K+ ATPase is altered in sickle cell disease (SCD), which affects serum electrolyte levels. This alteration is associated with several complications in sickle cell patients. This study evaluated the serum levels of sodium, potassium, and chloride in patients with SCD. The study was a case-control cross-sectional study involving 120 SCD patients in the steady state and 48 'healthy' controls. The SCD patients were made up of 69 HbSS patients and 41 HbSC patients. Serum electrolyte levels (Na+, K+, and Cl-) were measured using a Flame Atomic Absorption Spectrometer (Variant 240FS; Varian Australia Pty Ltd). Serum sodium levels were significantly lower in the sickle cell patients, compared with their 'healthy' counterparts (P = .0001). Although the study found significantly higher serum levels of potassium in the SCD patients (P = .0001), there was no significant difference in serum chloride levels between patients with SCD and the controls (P = .098). Serum sodium and chloride levels were not significantly different in both HbSS and HbSC patients (P = .197 and P = .553, respectively). The level of serum potassium in the HbSS patients was, however, significantly higher compared with those with the HbSC genotype (P = .0001). There is higher efflux of K+ from the intracellular into the extracellular space in HbSS patients, which may lead to red cell membrane dysfunction and associated complications.

Low nitric oxide level is implicated in sickle cell disease and its complications in Ghana.

BACKGROUND: Nitric oxide (NO) plays a fundamental role in maintaining normal vasomotor tone. Recent clinical and experimental data suggest that NO may play a role in the pathogenesis and therapy of sickle cell disease (SCD). The aim of this study was to determine NO metabolites (NOx) in SCD patients at steady state and in vaso-occlusive crisis (VOC), as well as those with hemolytic clinical sub-phenotype that includes leg ulcers and priapism. METHODOLOGY: This was a case-control cross-sectional study conducted on a total of 694 subjects including 148 comparison group HbAA, 208 HbSS SCD patients in steady state, 82 HbSC SCD patients in steady state, 156 HbSS SCD patients in VOC, 34 HbSC SCD patients in VOC, 34 HbSS SCD patients in post VOC, 21 HbSS SCD patients with leg ulcer and 11 HbSS SCD patients with priapism, with age ranging from 15 to 65 years. Laboratory diagnosis of SCD was done at the Sickle Cell Clinic of the Korle-Bu Teaching Hospital. Plasma nitric oxide metabolites were measured using Griess reagent system by ELISA method. RESULTS: Mean NOx of 59.66±0.75 µMol/L in the comparison group was significantly different from those in steady state (P=0.02). During VOC, there was a significant reduction in mean NOx levels to 6.08±0.81 µMol/L (P<0.001). Mean NOx levels were however, significantly higher (50.97±1.68 µMol/L) (P<0.001) in the immediate postcrisis period. The mean NOx levels in the leg ulcer (21.70±1.18 µMol/L) (P<0.001) and priapism (28.97±1.27 µMol/L) (P<0.001) patients were significantly low as compared to the SCD patients in the steady state and comparison group. CONCLUSION: This study presents the first report on plasma NOx levels in SCD complication in Ghanaian SCD patients and confirms reduced plasma NOx levels in SCD patients in general.

Correlation Between Soluble Endothelial Adhesion Molecules and Nitric Oxide Metabolites in Sickle Cell Disease.

Nitric Oxide (NO) and soluble adhesion molecules are promising biomarkers, which predict endothelial dysfunction in sickle cell disease (SCD). Several studies have investigated the relationship between NO (as well as its metabolites) and endothelial adhesion molecules in SCD. However, these studies were done mainly in the developed world, and it is difficult to extrapolate the findings to SCD populations in other geographical regions such as Africa due to significant disparities in the results. The aim of the current study was to determine the correlation between levels of nitric oxide metabolites (NOx) and adhesion molecules in SCD patients in a tertiary hospital in Ghana. A case control cross-sectional study involving 100 SCD (made up of HbSS and HbSC patients) and 60 healthy controls was conducted. Concentrations of NOx and soluble endothelial adhesion molecules (ICAM-1, VCAM-1 and E-selectin) were measured in all the study participants (n = 160) by the Griess reagent system and enzyme-linked immunosorbent assay (ELISA). Correlation analysis was performed to determine a possible link between the variables. Levels of soluble adhesion molecules were higher in the HbSS patients. Correlation of NOx with ICAM-1 almost approached significance (r = 0.565, p = 0.058) in the HbSS patients. There were no correlations between NOx and E-selectin in both HbSS and HbSC patients. There were no significant correlations between NOx and VCAM-1 in all the study participants (p > 0.05). Of the soluble adhesion molecules, ICAM-1 showed a significant positive correlation with VCAM-1 in the HbSC patients. There were no significant differences between the adhesion molecules and the age of participants in the various study groups. Whether or not a significant correlation exists between NOx and soluble adhesion molecules may not depend on the sickle cell genotype. The expression of adhesion molecules may not depend on age.

Hematological parameters in Ghanaian sickle cell disease patients.

BACKGROUND: Effective treatment and management of sickle cell disease (SCD) has been a challenge in Africa over the years. Hematological parameters are very useful profiles in the effective management of the disease. However, there is scarcity of studies on the hematological parameters of SCD in Ghana. This study aimed at determining hematological parameters among SCD patients with vaso-occlusion, those in the steady state as well as healthy controls at a teaching hospital in Ghana. METHODOLOGY: This was a cross-sectional study involving a total of 628 subjects, including 148 HbAA controls, 208 HbSS patients in steady state, 82 HbSC patients in steady state, 156 HbSS patients in vaso-occlusive crises (VOC), and 34 HbSC patients in VOC. Venous blood sample was collected from all study participants. A full blood count was done within 2 hours of collection, and hemoglobin (Hb) concentration, packed cell volume, red blood cell (RBC) concentration, mean corpuscular Hb, mean cell volume, mean corpuscular Hb concentration, and white blood cells (WBC) and platelet (PLT) counts were recorded. RESULTS: WBC and PLT counts were significantly higher in both female and male patients with SCD, compared with their healthy counterparts (P<0.05). The level of WBC was, however, significantly higher in patients with HbSS VOC among the SCD patients (P<0.001). Levels of Hb, RBC, and hematocrit were significantly higher in the controls (P<0.001). There was no significant difference in mean cell Hb among male patients with SCD (P=0.274) and female patients with SCD (P=0.5410). CONCLUSION: The SCD patients had lower Hb and RBC than the controls; however, higher PLT and WBC are noted in various status of SCD, possibly reflecting spleen effect in these patients. Further studies are needed to confirm these findings.