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This study explores the relationship between the development of uterine fibroids and hemoglobin SS sickle cell disease (SCD) by examining the prevalence of uterine fibroids as detected by pelvic magnetic resonance imaging (MRI) in African American (AA) women with and without SCD.A single-center, retrospective review was performed of all adult AA women at a large, academic medical center who received pelvic MRI from January 1, 2007 to December 31, 2018. Propensity score matching conditional on age and ZIP code evaluated the differences in fibroid prevalence between the two groups. Subanalyses by age in 10-year intervals were also performed.Twenty-one (23.9%) of 88 patients with SCD had fibroids on pelvic MRI versus 1493 (52.1%) of 2868 patients without SCD (p value0.001). After propensity score matching, 21 (24.7%) of 85 patients with SCD compared to 52 (61.2%) of 85 patients without SCD had fibroids (p value0.001). Subanalyses in 10-year age intervals showed significance for patients between 30 and 39 years old in which 4 (13.8%) of 29 SCD patients versus 374 (65.3%) of 573 no SCD patients had fibroids (p value0.001), and for patients between 40 and 49 years old in which 9 (42.9%) of 21 SCD patients versus 667 (73.8%) of 904 no SCD patients had fibroids (p value = 0.002).These findings indicate an overall significantly lower prevalence of uterine fibroids in AA women with SCD, suggesting that SCD may be protective against the development of uterine fibroids in these patients.

Thrombocytosis is common in sickle cell disease and may contribute to vaso‐occlusion. Hydroxyurea treats extreme thrombocytosis. Acquired von Willebrand disease should be considered prior to aspirin therapy.

Hemolytic blood disorders such as hemoglobinopathies are one of the most widespread diseases in our country. This paper reports non equilibrium thermodynamic analysis of adult normal hemoglobin subjected to variable frequency of electric fields in the range 0.1–100 MHz, comparing with homozygous hemoglobin SS and heterozygous hemoglobin SC. This is done applying some results obtained in non equilibrium thermodynamic field with internal variables. After a brief introduction, the phenomenological and state coefficients are explicitly calculated for the three hemoglobins, in function of the perturbation frequency. These values allow to calculate the proper functions of non equilibrium thermodynamics with internal variables. By comparing the calculated values for each hemoglobin, a new characterization of the protein was possible. Results were synthesized in six tables. People with heterozygous hemoglobin SC result from the inheritance of a beta(S)-globin gene from one parent and a beta(C)-globin gene from the other parent. It is found that there is a significant variation in dielectric parameters, possibly due to the hemoglobin structures and percentage.

BACKGROUND Sickle cell disease (SCD) is a disorder that results in increased hospitalizations and higher mortality. Advances in management have resulted in increases in life expectancy and led to increasing awareness of sickle cell hepatopathy (SCH). However, its impact in patients on the natural history and outcomes of SCD is not known. Our study aims to describe the prevalence of extreme hyperbilirubinemia (EH), one form of SCH, its effect on morbidity and mortality, and correlations between sickle cell genotype and SCH type. We hypothesize that EH is associated with higher morbidity and mortality. AIM To investigate the effects of EH on morbidity and mortality among patients with SCD. METHODS This retrospective cohort study was performed using a database of patients with SCD treated at Grady Memorial Hospital between May 2004 and January 2017. Patients with EH (defined as total bilirubin above 13.0 mg/dL) were identified. A control group was identified from the same database with patients with total serum bilirubin ≤ 5.0 mg/dL. Electronic medical records were used to extract demographic information, laboratory values, radiology results, current medications, need for transfusions and mortality data. Two samples T-test, chi-squared test and Fisher’s exact test were then used to compare the parameters between the two groups. RESULTS Out of the database, fifty-seven charts were found of patients with bilirubin > 13 mg/dL. Prevalence of severe SCH as defined by EH was 4.8% (57/1172). There were no demographic differences between patients with and without EH. Significant genotypic differences existed between the two groups, with hemoglobin SS SCD being much higher in the EH group (P < 0.001). Patients with severe EH had a significant elevations in alanine aminotransferase (157.0 ± 266.2 IU/L vs 19.8 ± 21.3 IU/L, P < 0.001), aspartate aminotransferase (256.5 ± 485.9 U/L vs 28.2 ± 14.7 U/L, P < 0.001) and alkaline phosphatase (218.0 ± 176.2 IU/L vs 85.9 ± 68.4 IU/L, P < 0.001). Patients with EH had significantly higher degree of end organ failure measured with quick Sequential Organ Failure Assessment scores (0.42 ± 0.68 vs 0.01 ± 0.12, P < 0.001), increased need for blood products (63% vs 5%, P < 0.001), and exchange transfusions (10.5% vs 1.3%, P = 0.022). CONCLUSION Among patients with SCD, elevated levels of total bilirubin are rare, but indicative of elevated morbidity, mortality, and need for blood transfusions. Large differences in sickle cell genotype also exist, but the significance of this is unknown.

Sickle cell disease (SCD) is a systemic hematological disease. Various genotypes of the disease exist; however, the two most common include hemoglobin SS (Hgb SS) and hemoglobin SC (Hgb SC) disease. Hgb SC is typically considered a less severe genotype; however, some patients with SC disease still have significant complications. Ektacytometry is utilized to measure red blood cell deformability in sickle cell patients and may help identify patients at risk for severe disease. We described a patient with genotype hemoglobin SC with a more severe phenotype, who we show to have very rigid red blood cells via ektacytometry.

Objectives To measure central macular thickness in Jordanian patients with sickle cell disease who did not have retinopathy and compare the findings with age- and sex-matched controls using spectral domain optical coherence tomography (SDOCT). Methods In this cross-sectional study, participants underwent visual acuity testing, slit-lamp bio-microscopy, dilated ophthalmoscopy, and SDOCT imaging to measure central macular thickness. Macular quadrant measurements and thickness difference indexes (TDIs) were compared between groups. Results Twenty eyes with sickle cell disease and 20 control eyes were enrolled. The median visual acuity in both groups was 20/20. The mean macular thickness was significantly lower in eyes with sickle cell disease than in matched controls (mean difference, 22.15 ± 6.44 µm). Peripheral quadrants were all significantly thinner in eyes with sickle cell disease, especially in superior and temporal quadrants. TDIs were lower in eyes with sickle cell disease than in control eyes. Conclusions Eyes with sickle cell disease that had no clinical evidence of retinopathy exhibited significantly lower central macular thickness in all quadrants, compared with eyes in age- and sex-matched controls. SDOCT is a non-invasive imaging modality that can detect preclinical changes in eyes with sickle cell disease and can be used to screen and monitor the disease process.

Background: Malaria placed a huge burden on human life and has been reported to be a key health problem affecting developing countries. This study was designed to assay for glucose-6-phosphate dehydrogenase (G6PD) status and malaria parasite density of individuals with sickle cell gene in University of Calabar Teaching Hospital, Calabar. Subjects and Methods: The methemoglobin method was used to determine the G6PD status. Thick blood films were used to ascertain the malaria parasite density while hemoglobin genotype was determined using cellulose acetate paper electrophoresis with tris ethylenediaminetetracetic acid borate buffer (pH 8.6). Thirty hemoglobin SS (HbSS) and 30 hemoglobin AS (HbAS) individuals were recruited for the study while 30 hemoglobin AA (HbAA) individuals were recruited as control. Results: The study showed a high frequency of G6PD deficiency (17.78%) in the study area while G6PD deficiency was significantly (P < 0.05) higher in HbAA individuals (33.33%) when compared to HbSS (10.00%) and HbAS (10.00%) individuals. The prevalence of malaria parasitemia and parasite density was comparable in the three hemoglobin variants. The distribution of malaria parasitemia and parasite density in both gender among the various hemoglobin variants showed no association (P > 0.05). G6PD deficiency distribution in both gender were found to be comparable (P > 0.05). The distribution of malaria parasitemia in the various hemoglobin variants in the G6PD-deficient individuals showed no significant difference (P > 0.5). However, the parasite density of the HbAS (3100 ± 1828.48 μL) and HbSS (2400 ± 1687.06 μL) were significantly lower than that of HbAA (4040 ± 1529.44 μL). Conclusion: The result of this study supports the hypothesis that inheriting the G6PD deficiency gene and sickle cell gene (both in homozygous and heterozygous form) reduces the severity of malaria parasite infection and hence protects against severe acute malaria while having less effect on infection.

Introduction: Sickle cell anemia (SCA) is one of the most common genetic diseases worldwide. Patients with SCA present with varied clinical features and complications that may affect many organs in the human body. There are few treatment options for SCA, and patient responses vary; the only curative therapy is a stem cell transplant or gene therapy. We seek to study the clinical features and treatment options for patients with sickle cell disease treated in King Abdulaziz Medical City, Riyadh. Methods: This study was a retrospective cohort study of all adult SCA patients who were admitted to our institution during the period from 1983 to 2016. Data were entered into Excel spreadsheets and managed with SPSS. Chi-square test was used to compare responses to therapy and in patients with different presentations. Results: A total of 106 patients with sickle cell disease were included in this study. The percentages with respect to hospital admissions per year were as follows: 34.9% (37 patients) were never admitted, 26.4% (28 patients) were admitted fewer than 2 times, 24.5% (26 patients) were admitted 3–5 times, and 13.2% (14 patients) were admitted more than 5 times. The number of complications was used to measure the severity of the disease. The disease severity was higher in males than in females (67.3% vs. 32.7%, respectively; P = 0.018). The disease severity was higher in those who were born in the Western and Southwestern areas than in other areas (84.2% vs. 15.8%, respectively; P = 0.007). Hydroxyurea significantly reduced the severity of SCA with a P = 0.002. Conclusion: Our study showed that vaso-occlusive crisis was the most common complication and indication for hospital admission. Treatment with hydroxyurea led to a significant reduction in the number of hospital admissions.

Liver abscesses are poorly known in sickle cell disease. We report here multiple liver abscesses occurring in a 17-year-old patient with hemoglobin SC disease. A Fusobacterium nucleatum was identified on cyst puncture. Such complications have been described in only 11 children and young adults with hemoglobin SS/Sβ-thalassemia diseases. Fusobacterium species are the most frequent pathogens reported and require anaerobic culture to be identified.

Objectives Automated red blood cell exchange (RBX) is an important treatment for patients with sickle cell disease (SCD). Although not specifically targeted for removal, platelets (PLTs) are collected along with red blood cells during RBX. We sought to determine whether the pre- and post- RBX PLT counts could be used to derive the post-procedure hemoglobin S% (HgbS%). Methods Using the pre- and post- RBX lab values of 59 SCD patients undergoing 112 RBX procedures over 1 year, we derived mathematical formulas which estimate the post-RBX HgbS% based on the pre-RBX HgbS%, the pre- and post- RBX PLT, and a correction factor. Results For patients with pre-RBX HgbS > 40%, the mathematically derived post-RBX HgbS% was statistically indistinguishable from the measured post-RBX HgbS%. Conclusions Using a simple formula, pre- and post-RBX platelet counts can provide a rapid approximation of the measured post-RBX HgbS% in patients with SCD.

Introduction Sickle cell disease (SCD) is the most common inherited blood disorders in the United States. The disease predominantly affects African Americans with 1 out of every 365 individuals born with SCD. The disease is characterized by vascular inflammation and vaso-occlusion leading to numerous complications and multi-organ dysfunction. Previous studies have shown women with SCD tend to outlive their male counterparts. Other than the increased life expectancy, sex-based clinical outcome differences in SCD remain largely unknown. To better characterize sex-based differences in SCD, we assessed sociodemographic characteristics, pain, treatment characteristics, laboratory measures and complications among males and females currently enrolled in the Sickle Cell Disease Implementation Consortium (SCDIC) registry. Methods The SCDIC consists of eight academic and comprehensive SCD centers, and one data-coordinating center that received funding from the National Heart Lung and Blood Institute to improve outcomes for individuals with SCD. Participants were eligible for the enrollment in the SCDIC registry if they were 15 to 45 years of age and had a confirmed diagnosis of SCD. Participants were excluded if they had sickle cell trait or had a successful bone marrow transplant. Enrolled participants completed surveys. Data were also abstracted from the participants' medical records. Data were entered into a REDCap database and analyzed using SAS version 9.4 (SAS Institute; Cary, NC). Categorical variables were presented as frequencies and percentages, continuous variables were presented as medians and interquartile ranges (IQR) or means and standard deviations. Categorical variables were analyzed using Chi-Square or Fisher exact tests when appropriate. Continuous variables were compared using the Mann-Whitney U test or independent sample t-tests depending on the distribution. A two-sided p-value less than 0.05 was deemed significant. Results A total of 2,124 participants were included in the study. The mean (SD) age of our participants was 27.8 (7.9) years. Almost all (95.6%) were Africa American, female (56%) and had hemoglobin SS (68.2%) SCD genotype. More males (55.4 % vs. 44.6%, p Conclusion Key differences in SCD presentation and occurrence of complications exist among males and females. Females had higher rates of depression and anxiety while males had more chronic end-organ complications that are life threatening. Our findings emphasize the need for stratification of data analysis by sex in future SCD studies. Disclosures Hankins: Global Blood Therapeutics: Consultancy, Research Funding; National Heart, Lung, and Blood Institute: Honoraria, Research Funding; LINKS Incorporate Foundation: Research Funding; American Society of Pediatric Hematology/Oncology: Honoraria; MJH Life Sciences: Consultancy, Patents & Royalties; UptoDate: Consultancy; Novartis: Research Funding. Treadwell:UpToDate: Honoraria; Global Blood Therapeutics: Consultancy. King:Tioma Therapuetics: Consultancy; WUGEN: Current equity holder in private company; RiverVest: Consultancy; Celgene: Consultancy; Cell Works: Consultancy; Incyte: Consultancy; Magenta Therapeutics: Membership on an entity's Board of Directors or advisory committees; Bioline: Consultancy; Novimmune: Research Funding; Amphivena Therapeutics: Research Funding. Gordeuk:CSL Behring: Consultancy, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; Imara: Research Funding; Ironwood: Research Funding; Novartis: Consultancy. Kanter:bluebird bio, inc: Consultancy, Honoraria; SCDAA Medical and Research Advisory Board: Membership on an entity's Board of Directors or advisory committees; AGIOS: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy; Sanofi: Consultancy; Medscape: Honoraria; Guidepoint Global: Honoraria; GLG: Honoraria; Jeffries: Honoraria; Cowen: Honoraria; Wells Fargo: Honoraria; NHLBI Sickle Cell Advisory Board: Membership on an entity's Board of Directors or advisory committees; BEAM: Membership on an entity's Board of Directors or advisory committees. Glassberg:Eli Lilly and Company: Research Funding; Pfizer: Research Funding; Global Blood Therapeutics: Consultancy. Shah:Bluebird Bio: Consultancy; Novartis: Consultancy, Research Funding, Speakers Bureau; Global Blood Therapeutics: Consultancy, Research Funding, Speakers Bureau; CSL Behring: Consultancy; Alexion: Speakers Bureau.

Sickle cell disease (SCD) patients are thought to be at higher risk for urinary tract infections (UTIs) compared to the general population secondary to increased sickling, abnormal urinary acidification, and an inability to concentrate the urine. The incidence of UTI in febrile children with SCD in the United States is unknown. Our objectives were to determine the rate of UTI among febrile SCD children and describe the risk factors for UTI in this population. We conducted a retrospective chart review of all febrile SCD patients &lt, 4 years of age who presented to a pediatric emergency department from 2012&ndash, 2017 and who had a sterile sample of urine for analysis. A total of 167 febrile patients with SCD with 464 visits were identified. The majority were African American (95.2%), female (58.7%), and had hemoglobin SS (HbSS) (65.3%). The rate of UTI was 4.1%. All patients with a UTI were African American females with a median age of 19 months (IQR 12&ndash, 30). On regression analysis, no risk factors were associated with a UTI. We found the rate of UTI in febrile young children with SCD was comparable to non-SCD children. Larger studies are required to identify the presence of risk factors for UTI in this population.

In the last decades the exposure to human-made electromagnetic fields is strongly increased. Considering that all biological tissues interact with electromagnetic it is clear that more studies are needed to deepen the knowledge acquired to date on the effects on human health. This paper study the waves propagation on differently substituted hemoglobins, homozygous hemoglobin SS and heterozygous hemoglobin SC comparing with adult normal hemoglobin AA. After recall briefly the non-equilibrium thermodynamic theory with internal variables, we introduce the explicit form of the phenomenological and state coefficients as function of the perturbation frequency by mean of which we determine the real and imaginary part of the wave number K and the phase velocity of the wave for the three solutions. The difference between them suggests the beta 6 amino acid substitution as the main prerequisite for these variations. The results obtained from the application of our mathematical model can contribute to the interpretation of the structural functionality of the different hemoglobins and improve the development of biomedical applications in diagnostic and therapeutic technologies.

Background Expert guidelines recommend that hydroxyurea (HU) be offered to all children with hemoglobin SS and Sβ0 sickle cell disease (SCD) and be considered for children with clinically severe hemoglobin SC or Sβ+. This study aims to determine the rate of HU use in hospitalized children, if HU is differentially used in children with clinically severe SCD, and if HU users have shorter length of stay (LOS), fewer intensive care unit (ICU) admissions, and fewer inpatient transfusions compared to nonusers. Procedure Using the Pediatric Health Information System, we performed a retrospective analysis of children ages 2–18 years with SCD discharged between January 1, 2011 and September 30, 2014. We defined patients as having clinically severe SCD if they had a recent ICU admission or ≥3 admissions in the preceding year. Results Of the 2,665 unique children identified, approximately 80% had an inpatient code indicating HU use. Significantly more (p < 0.001) nonusers (30.1%) had a recent ICU admission compared to HU users (18.7%). More nonusers (33.9%) had a history of ≥3 admissions compared to HU users (21.5%) (p < 0.001). After applying propensity score weighting, the groups did not differ in their LOS, prevalence of ICU admissions, or prevalence of transfusions. Conclusions HU use is high among hospitalized children with SCD. However, HU is not utilized by many children with clinically severe SCD. These results support that HU be considered in children with SCD to prevent hospitalization rather than as a treatment to improve hospitalization outcomes.

Moyamoya, a pattern of progressive stenosis of the ICA associated with secondary formation of collateral vessels at the base of the brain, is a rare but well described cerebral vasculopathy. Moyamoya can be idiopathic but is also associated with several genetic disorders, inflammatory conditions and radiation exposure. Despite extensive research on the topic, the underlying mechanisms for how and why Moyamoya develops are not well understood. Moyamoya syndrome in sickle cell disease is one of the more studied subsets of the disease and recent experience with this subtype may have implications for understanding of all types of Moyamoya. Treatment options for Moyamoya are limited, with the mainstays of therapy restricted to surgical revascularization procedures.

A total of 126 patients were included in the study- 65 girls and 61 boys. The mean age of the subjects was 8 ± 4 years (ranging from three to sixteen years). The most represented age group was that from 3-4 years of age. Most of the participants were from the Central Region (46%). All of the subjects were homozygous for hemoglobin SS. Subjects with yearly frequency of three vaso-occlusive crises represented 42.9% of the sample. 57.9% of the patients had been polytransfused within the past 3 years (>2 transfusions). Up to 45.2% of the patients had been hospitalized within the past year.

Sickle cell anemia (SCA) is an inherited disorder of hemoglobin due to the presence of abnormal hemoglobin in a homozygous state. Manifestation is usually in infancy or early childhood due to gradual decrease in hemoglobin F level as age advances. Diagnosis in middle age is unusual. We present a woman who was diagnosed of SCA for the first time at middle age. The aim was to bring to the knowledge of physicians that patients with SCA can also present late so high index of suspicion is required to make diagnosis. A 52-year-old woman presented to orthopedic clinic with complaints of generalized bone pain and low back pain. There was no history of trauma prior to the onset of the pain. There was no associated fever, weight loss, loss of appetite, nor weakness of the lower limbs. X-ray of the spine done showed wedge collapse of the 12th thoracic and first lumbar vertebrae with posterior angulation of the thoracolumbar junction giving dorsal kyphosis. Her mode of presentation raised a suspicion of tuberculosis of the spine to rule out multiple myeloma. However, investigations for tuberculosis and multiple myeloma were all negative. This necessitated the investigation for SCA and the diagnosis was confirmed. The diagnosis of SCA is usually made in infancy or early childhood. High index of suspicion is required to make the diagnosis at middle age.

a b s t r a c t Objective: The aim of the present study was to characterize sickle cell disease retinopathy in children and teenagers from Bahia, the state in northeastern Brazil with the highest incidence and prevalence of sickle cell disease. Methods: A group of 51 sickle cell disease patients (36 hemoglobin SS and 15 hemoglobin SC) with ages ranging from 4 to 18 years was studied. Ophthalmological examinations were performed in all patients. Moreover, a fluorescein angiography was also performed in over 10-year-old patients. Results: The most common ocular lesions were vascular tortuosity, which was found in nine (25%) hemoglobin SS patients, and black sunburst, in three (20%) hemoglobin SC patients. Peripheral arterial closure was observed in five (13.9%) hemoglobin SS patients and in three (13.3%) hemoglobin SC patients. Arteriovenous anastomoses were present in six (16.5%) hemoglobin SS patients and six (37.5%) hemoglobin SC patients. Neovascularization was not identified in any of the patients. Conclusions: This study supports the use of early ophthalmological examinations in young sickle cell disease patients to prevent the progression of retinopathy to severe disease and further blindness. © 2014 Associac ¸a o Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published

Hematopoietic stem cell transplant (HSCT) is the only cure for sickle cell disease (SCD). HSCT using an HLA-identical sibling donor is currently an acceptable treatment option for children with severe SCD, with expected HSCT survival >95% and event-free survival >85%. HSCT for children with less severe SCD (children who have not yet suffered overt disease complications or only had mild problems) is controversial. It is important to consider the ethical issues of a proposed study comparing HLA-identical sibling HSCT to best supportive care for children with less severe SCD. In evaluating the principles of nonmaleficence, respect for individual autonomy, and justice, we conclude that a study of HLA-identical sibling HSCT for all children with SCD, particularly hemoglobin SS and Sβ0-thalassemia disease, is ethically sound. Future work should explore the implementation of a large trial to help determine whether HSCT is a beneficial treatment of children with less severe SCD.

The known biophysical variations of hemoglobin (Hb) S and Hb C may result in hemodynamic differences between subjects with SS and SC disease. The purpose of this study was to measure and compare conjunctival hemodynamics between subjects with Hb SS and SC hemoglobinopathies. Image sequences of the conjunctival microcirculation were acquired in 9 healthy control subjects (Hb AA), 24 subjects with SC disease, and 18 subjects with SS disease, using a prototype imaging system. Diameter (D) and blood velocity (V) measurements were obtained in multiple venules of each subject. Data were categorized according to venule caliber by averaging V and D for venules with diameters less than (vessel size 1) or greater than (vessel size 2) 15 µm. V in vessel size 2 was significantly greater than V in vessel size 1 in the AA and SS groups (P ≥ 0.009), but not in the SC group (P = 0.1). V was significantly lower in the SC group as compared to the SS group (P = 0.03). In AA and SS groups, V correlated with D (P ≤ 0.005), but the correlation was not statistically significant in the SC group (P = 0.08). V was inversely correlated with hematocrit in the SS group for large vessels (P = 0.03); however, no significant correlation was found in the SC group (P ≥ 0.2). Quantitative assessment of conjunctival microvascular hemodynamics in SS and SC disease may advance understanding of sickle cell disease pathophysiology and thereby improve therapeutic interventions. Am. J. Hematol. 88:661–664, 2013. © 2013 Wiley Periodicals, Inc.

Vaso-occlusive crisis (VOC) is a complex process that occurs in patients with sickle cell disease (SCD) and is often associated with pain and urgent hospitalization. A major instigator of VOC is microvascular obstruction by pathologically stiffened sickle red blood cells (RBCs), and thus therapy relies heavily on optimizing intravenous fluid (IVF) hydration to increase RBC deformability. However, no evidence-based guidelines regarding the choice of IVF currently exist. We therefore analyzed alterations in biomechanical properties of sickle RBCs isolated from patients with homozygous SCD (hemoglobin SS) after exposure to different osmolarities of clinical IVF formulations. Atomic force microscopy (AFM) was used to assess stiffness of RBCs after exposure to different IVFs. A microfluidic model of the human capillary system was used to assess transit time and propensity to occlusion after exposure to the different IVF formulations. Sickle RBCs exposed to normal saline (NS) had increased stiffness, transit times, and propensity to microchannel occlusion compared to other osmolarities. Normal saline, an IVF formulation often used to treat patients with SCD during VOC, may induce localized microvascular obstruction due to alterations of sickle RBC biomechanical properties. This article is protected by copyright. All rights reserved.

Objective: To identify and characterize hospital admissions and readmissions in the Brazilian Unified Public Health System (Sistema Único de Saúde [SUS]) in children with sickle cell disease diagnosed by the Minas Gerais Newborn Screening Program between 1999 and 2012. Methods: Hospital Admission Authorizations with the D57 (International Classification of Diseases-10) code in the fields of primary or secondary diagnosis were retrieved from the SUS Databank (1999–2012). There were 2991 hospitalizations for 969 children. Results: 73.2% of children had hemoglobin SS/Sβ0-thalassemia and 48% were girls. The mean age was 4.3 ± 3.2 years, the mean number of hospitalizations, 3.1 ± 3.3, and the hospital length of stay, 5 ± 3.9 days. Hospital readmissions occurred for 16.7% of children; 10% of admissions were associated with readmission within 30 days after discharge; 33% of readmissions occurred within seven days post-discharge. There were 41 deaths, 95% of which were in-hospital. Secondary diagnoses were not recorded in 96% of admissions, making it impossible to know the reason for admission. In 62% of cases, hospitalizations occurred in the child's county of residence. The total number of hospitalizations of children under 14 with sickle cell disease relative to the total of pediatric hospitalizations increased from 0.12% in 1999 to 0.37% in 2012. Conclusions: A high demand for hospital care in children with sickle cell disease was evident. The number of hospitalizations increased from 1999 to 2012, suggesting that the disease has become more “visible.” Knowledge of the characteristics of these admissions can help in the planning of care for these children in the SUS. Resumo: Objetivo: Identificar e caracterizar as internações e reinternações hospitalares no Sistema Único de Saúde (SUS) de crianças com doença falciforme, diagnosticadas pelo Programa de Triagem Neonatal de Minas Gerais entre 1999 e 2012. Métodos: Extraíram-se do banco de dados do SUS as Autorizações de Internação Hospitalar com o código D57 (Classificação Internacional de Doenças10) nos campos de diagnóstico primário ou secundário (1999-2012). Identificaram-se 969 crianças, totalizando 2.991 internações. Resultados: 73,2% das crianças tinham hemoglobina SS/Sβ0- talassemia e 48% eram meninas. A média de idade foi de 4,3 ± 3,2 anos, a do número de internações, 3,1 ± 3,3 e a do tempo de permanência, 5 ± 3,9 dias. As readmissões hospitalares ocorreram em 16,7% das crianças; 10% das internações se associaram à readmissão em até 30 dias pós-alta; 33% das readmissões ocorreram em até 7 dias pós-alta. Ocorreram 41 óbitos, 95% em ambiente hospitalar. O diagnóstico secundário não foi registrado em 96% das internações, impossibilitando conhecer o motivo da internação. Em 62% dos casos, as internações ocorreram no município de residência da criança. O total de internações de crianças até 14 anos com doença falciforme em relação ao total das internações pediátricas passou de 0,12% em 1999 para 0,37% em 2012. Conclusões: Constatou-se elevada demanda por cuidados hospitalares, cujo aumento relativo entre 1999 e 2012 sugere incremento da “visibilidade” da doença falciforme. O conhecimento das características dessas internações pode contribuir no planejamento do cuidado na rede assistencial do SUS. Keywords: Sickle cell disease, Hospital Admitting Department, Epidemiology, Health system, Newborn screening, Brazil, Palavras-chave: Doença falciforme, Serviço Hospitalar de Admissão de Pacientes, Epidemiologia, Sistema Único de Saúde, Triagem neonatal, Brasil

The aim of this study was to estimate the prevalence of hemoglobinopathies in South Brazil.Samples of dried blood spots collected by heel prick in neonates were evaluated by isoeletric focusing and/or high-performance liquid chromatography techniques. All variants were characterized at the molecular level.A total of 437,787 samples were evaluated. Among these, 6391 showed an abnormal hemoglobin pattern. These included 48 cases (0.01%) of sickle cell disorders (33 hemoglobin SS [Hb SS], 7 Hb SC, 7 Hb S/beta thalassemia, 1 Hb SD), 1 neonate who was homozygous for beta thalassemia, 6272 (1.4%) newborns who were heterozygous for Hb S, C, or D, and 71 (0.02%) neonates who were carriers for rare hemoglobin variants. Most of these rare variants were identified for the first time in Brazil.Comparing these results with those obtained in other Brazilian regions, we observe a highly heterogeneous distribution. This knowledge is useful in healthcare planning and allocation of resources, as well as identifying at-risk couples, which will assist with disease prevention.

Objectives: To determine the effect of intravenous (IV) magnesium sulfate on the length of stay (LOS) for children admitted with sickle cell pain crisis. Methods: This was a single arm study, with historical controls. Hemoglobin SS or Hemoglobin Sb8 children admitted for pain crisis were eligible. Two sequential treatment protocols of IV magnesium sulfate were added to standard inpatient therapy of IV fluids, opioids, and nonsteroidal anti-inflammatory drugs. The initial 12 children received 40 mg/kg (maximum of 1.5 g) of IV magnesium in the emergency department (ED), and eight and 16 hours later. Seven subsequent children received 40 mg/kg (maximum of 2.5 g) of IV magnesium in the ED, and every eight hours for up to four inpatient days. The main outcome measure was LOS, measured in days. Differences in LOS were analyzed between the admission with magnesium, and the two previous admissions meeting the same criteria, using a Wilcoxon signed-rank test for nonparametric paired data. Results: Nineteen children were enrolled. The results of the two protocols were combined for the analysis. A shorter LOS was found on study admissions (median LOS, 3.0 days compared with 5.0 and 4.0 days for the previous two admissions; p = 0.006). Conclusions: IV magnesium appears to decrease the LOS for children with sickle cell pain crisis. Key words: sickle cell anemia; magnesium; length of stay. ACADEMIC EMERGENCY MEDICINE 2004; 11:968‐972.

BACKGROUND: Sickle cell disease (SCD) describes a group of inherited red blood cell disorders. People with SCD have abnormal haemoglobin (Hb), called Hb S. In all forms of SCD, at least one of the two abnormal genes causes a person's body to make Hb S. In countries with limited resources, diagnostic technique should be simple and easy to perform with high sensitivity and specificity. METHODS: This study compared the paperbased sickle cell test and sodium metabisulfite sickling test using Hb electrophoresis as a gold standard. It was a crosssectional hospitalbased study which was conducted from July to October 2017 involving a total of 140 blood samples of under 10 years children presumed to have SCD. Blood samples in ethylenediaminetetraacetic acid anticoagulantcontaining vacutainers were used for SCD diagnosis by using paperbased and sodium metabisulfite sickling tests then confirmed by Hb electrophoresis as the gold standard. RESULTS: Blood specimens were from individuals aged 4 years ranged from 2 to 9 years. Slightly majority of blood specimens belonged to males, 54.3% (76/140) while the majority was from inpatients, 82.9% (116/140). Paperbased sickle cell test identified 46/140 (32.9%) Hb AA, 81/140 (57.9%) Hb, and 6/140 (4.3%) Hb AS. Sickling test identified 50/140 (35.7%) Hb AA and 87/140 (62.1%) Hb SS. Hb electrophoresis identified 50/140 (35.7%) Hb AA, 83/140 (59.3%) Hb SS, and 7/140 (5%) Hb AS. The paperbased sickle cell test had a sensitivity of 97.8% and specificity of 96.7% while the sickling test had the sensitivity of 96.7% and specificity of 100%. CONCLUSION: Paperbased sickle cell test was able to detect sickle cell carriers, Hb AS and shown high sensitivity and specificity; therefore, it can be used as a substitute for sickling test in countries with limited resource. However, paperbased sickle test is suitable for adults' population.

Objectives This cross-sectional study examines to whom and how fully sickle cell disease (SCD) patients talk to others about sickle cell pain, how helpful it is to talk with others about these pain episodes, and the association between talking to others about sickle cell pain episodes and patients' psychological adjustment and coping strategies in managing the disease. Methods A convenience sample of 73 African American patients with SCD (30 men and 43 women), were recruited from two SCD clinics at the time of routine medical visits. Most participants had been diagnosed with hemoglobin SS, and they reported an average number of 8.61 pain episodes in the previous 12 months. Participants were asked to whom, how fully, and how helpful it was to talk to significant others about SCD pain episodes experienced in the last 12 months. Patients also completed measures of their psychological adjustment as well as how they would manage a future sickle cell pain episode. Self-report ratings were made on Likert-type scales. Results Based on paired samples t-tests, participants talked significantly more fully about their thoughts and feelings concerning pain episodes to God and to their primary medical providers than to either their parents, siblings, or an intimate partner/close friend. Bivariate correlations indicated that amount and helpfulness of talking about pain episodes to God and to parents were significantly associated with better psychological adjustment on selected measures. Also, bivariate correlations indicated that helpfulness in talking with siblings, intimate partner/close friend, and primary medical providers was positively related with willingness to go to a physician in the event of a future pain episode. Conclusions The results document to whom and how helpful it is to talk with others about SCD pain episodes and how SCD disclosure is related to strategies for managing this disease.

OBJECTIVE: To evaluate complications in pregnant women with sickle cell disease, especially those leading to maternal death or near miss (severe obstetric complications). METHODS: A prospective cohort of 104 pregnant women registered in the Blood Center of Belo Horizonte (Hemominas Foundation) was followed up at high-risk prenatal units. They belonged to Group I (51 hemoglobin SS and three hemoglobin S/ß0-thalassemia) or Group II (49 hemoglobin SC and one hemoglobin S/ß+-thalassemia). Both groups had similar median ages. Predictive factors for 'near miss' or maternal death with p-value = 0.25 in the univariate analysis were included in a multivariate logistic model (significance set for p-value = 0.05). RESULTS: Group I had more frequent episodes of vaso-occlusive crises, more transfusions in the antepartum and postpartum, and higher percentage of preterm deliveries than Group II. Infections and painful crises during the postpartum period were similar in both the groups. The mortality rate was 4.8%: three deaths in Group I and two in Group II. One-third of the women in both the groups experienced near miss. The most frequent event was pneumonia/acute chest syndrome. Alpha-thalassemia co-inheritance and ß-gene haplotypes were not associated with near miss or maternal death. In multivariate analysis predictors of near miss or death were parity above one and baseline red blood cell macrocytosis. In Group I, baseline hypoxemia (saturation < 94%) was also predictive of near miss or death. CONCLUSION: One-third of pregnant women had near miss and 4.8% died. Both hemoglobin SS and SC pregnant women shared the same risk of death or of severe complications, especially pulmonary events.

Increasing hemoglobin F (HbF) appears to be beneficial for patients with sickle cell anemia. We previously demonstrated that daily, oral sodium phenylbutyrate (OSPB) induces HbF synthesis in pediatric and adult patients with hemoglobin SS (HbSS). The high doses and need for daily therapy, however, have limited its use. Here, we report a patient treated with pulsed-dosing of OSPB for over 3 years. This patient developed a modest, but sustained elevation in HbF over the course of therapy without side effects. Although larger studies are needed, this case demonstrates that pulsed-dosing with OSPB enhances HbF synthesis. Pediatr Blood Cancer 2008;50:357–359. © 2007 Wiley-Liss, Inc.

OBJECTIVE Sickle cell disease comprises chronic, genetically determined disorders, presenting significant morbidity and high prevalence in Brazil. The goal of this study was to evaluate the quality of life of sickle cell disease patients (hemoglobin SS and SC) and their sociodemographic and clinical characteristics. METHODS Data was collected from clinical records and semi-structured interviews consisting of clinical questionnaires and the World Health Organization Quality of Life-brief questionnaire. RESULTS Interviews were conducted with 400 patients, aged between 18 and 72, treated in the Fundação HEMOMINAS in Belo Horizonte. The participants predominantly had sickle cell disease hemoglobin SS variant (65.5%), were female (61.8%), single (55.3), with up to 8 years of schooling (49.6%), and self-defined as mulattos (50%). Pain crises, hospitalizations, blood transfusions, and other morbidities of sickle cell disease had a significant impact on the quality of life of these patients. CONCLUSION Within this group, the social profile was that of low income and unemployed with sickle cell disease considered to be a significant impediment to finding a job. Evaluating quality of life as a determining factor of health is essential for the creation of specific policies and measures, appropriate for the specific characteristics and social context of sickle cell disease.

Hemoglobin SO-Arab is a rare sickling disorder with a clinical course similar to that of hemoglobin SS. Hemoglobin C-Harlem is another rare condition that produces sickling disorders in affected individuals with a disease course and electrophoretic findings similar to that of hemoglobin SO-Arab. The authors report the case of a 38-year-old African American man with hemoglobin SO-Arab and the challenges that may arise in working up a rare hemoglobinopathy.

We studied the number and function of angiogenic progenitor cells and growth factors in children aged 5–18 years without acute illness, 43 with Hemoglobin SS and 68 with normal hemoglobin. Hemoglobin SS subjects had at least twice as many mononuclear cell colonies and more circulating progenitor cell than Control subjects. Plasma concentrations of erythropoietin, angiopoietin-2, and stromal-derived growth factor (SDF)-1αwere significantly higher in children with Hemoglobin SS compared to Control subjects. In a multivariate analysis model, SDF-1αconcentration was found to be associated with both CPC number and total white blood cell count in the Hemoglobin SS group, suggesting that SDF-1αproduced by ischemic tissues plays a role in mobilizing these cells in children with Hemoglobin SS. Despite having a higher number of angiogenic progenitor cells, children with Hemoglobin SS had slower migration of cultured mononuclear cells.

A 10-year-old male patient with hemoglobin SS suffered a stroke at 7 years of age and was initially transfused at the time of presentation to lower the hemoglobin S concentration to < 30%. You are asked by the family if their child can be treated with oral hydroxyurea rather than monthly transfusions for the secondary prevention of strokes.

Complications involving the central nervous system are among the most devastating manifestations of sickle cell disease. Although overt stroke occurs in 1 in 10 children with Hemoglobin SS, “silent cerebral infarcts” are even more frequent. Both are associated with significant neuropsychological deficits. The end result of these effects on the CNS often is diminished school performance. The use of transcranial Doppler ultrasonography screening allows the identification of patients at high risk for clinical stroke as well as stroke prevention by chronic transfusion. However, definitive prophylaxis and treatment for most CNS complications of sickle cell disease have yet to be determined.

Optimal folate status of sickle cell disease (SCD) patients might be important because these patients have an inherent high risk of endothelial damage. Serum folate, erythrocyte folate, and plasma homocysteine are used as static and functional markers of folate status. We recently investigated the folate status of SCD patients (1) and subsequently established the dosages needed for optimal daily supplementation (Van der Dijs et al., submitted for publication). The daily intakes were progressively increased during 70 weeks. During dose escalation, we observed different responses for red blood cell (RBC) folate, but not serum folate, in hemoglobin SS (HbSS) and HbSC patients. These subgroups did not differ in RBC folate at baseline, but the folate concentrations of HbSS patients increased to reach a higher steady state after supplementation. Steady-state …

Translocation renal cell carcinoma (RCC) is a family of rare tumors recently identified in the pediatric and young adult population. We report the first case of a young woman from French West Indies with sickle cell anemia who developed a translocation RCC t(6;11)(p21;q12). Usually people with the sickle cell condition are known to develop renal medullary carcinoma (RMC). To our knowledge, this is the first case described in the literature of a translocation RCC associated with sickle cell disease. Here we discuss the relation between translocation RCC, RMC, and sickle cell disease.

Abstract 846 Elevation of the serum level of secretory phospholipase A2 (sPLA2) has previously been reported to predict impending acute chest syndrome (ACS) in sickle cell disease (SCD) patients admitted with pain. The Sickle Cell Disease Clinical Research Network initiated the PROACTIVE Feasibility Study to 1) assess the feasibility of screening, randomizing and treating with simple transfusion eligible patients and 2) assess the predictive utility of sPLA2 in screening for imminent ACS, characterize the distribution of sPLA2 values in sickle cell patients hospitalized with pain, and define a cut-off point for predicting ACS to optimize its reliability, sensitivity and specificity in predicting ACS. All SCD patients (hemoglobin SS, SC and SBeta-thalassemia) admitted for pain at a participating center were to be screened for eligibility; patients with a diagnosis of ACS at entry were not eligible. sPLA2 levels were drawn daily on consenting patients for up to three days during the admission. All patients had at least one CXR (mandated at 72 hr if not done for clinical indications) during the course of their hospital stay to determine if they had developed a new infiltrate, considered diagnostic for ACS. Patients who developed T>38°C, a sPLA2 level > 100ng/ml and had a normal CXR were eligible for randomization to observation or simple transfusion; the remaining patients were followed in an Observation arm. Of 421 patients potentially eligible for screening, 238 were enrolled in the study with 10 of these patients randomized (4 to transfusion 6 to standard care). Of these, 203 patients had from one to three sPLA2 levels drawn prior to an ACS diagnosis or did not develop ACS; if transfused, they received blood only after a diagnosis of ACS was made. Twenty-two of these patients (11%) developed ACS. Analysis of the maximum sPLA2 levels prior to ACS diagnosis revealed that a threshold of 45 ng/ml was the most accurate level to predict ACS (accuracy: 73%, sensitivity: 73%, specificity: 73%). The positive predictive value (PPV: 25%) was low due to the relative infrequency of ACS events. When sPLA2 levels were analyzed in children versus adults, sPLA2 was more accurate for adults in predicting ACS with a level of 65ng/ml having accuracy: 88%, sensitivity: 44%, specificity: 95%, PPV: 57%. The addition of a requirement for fever did not improve the accuracy of sPLA2 in either adults or children. Further analysis of sPLA2 levels with various clinical and laboratory data is ongoing to improve the PPV of sPLA2. These results indicate that sPLA2 can predict ACS with good sensitivity, but may require additional parameters to be useful in clinical management of SCD patients admitted with pain and at risk for ACS. Supported by the NHLBI. Disclosures: Labotka: HemaQuest Pharmaceuticals, Inc: Research Funding.

The relationship between brain injury and vasculopathy in 146 sickle cell (SCD) patients with hemoglobin SS, the most serious form of SCD, was evaluated by MRI and MRA at St Jude Children’s Research Hospital, Memphis, TN.

A simple and sensitive immunochemical method for quantifying hemoglobins A1, S and F is described. Antibodies to human hemoglobins A1, S and F were obtained in goats and after cross absorption were shown to be specific for thei corresponding hemoglobins. These specific antisera were employed in a radial immunodiffusion method to quantify hemoglobins A1, S and F in hemoglobin specimens of known phenotype as ascertained by electrophoresis on cellulose acetate. The method accurately quantifies hemoglobins in purified hemoglobin mixtures designed to simulate expected proportions in newborn infants who have sickle cell trait or sickle cell anemia. Principal application of this methodology currently under consideration are in diagnosis of hemoglobin SS in the infanct and studies on rates of development change in hemoglobins A1, S and F.

The psychologic effect of sickle cell anemia, a life-long chronic illness, on the self-concept, anxiety level, and personal and social adjustments of school-aged children was investigated by using a battery of standard psychologic tests. Two groups of children were evaluated: a study group of 29 children with sickle cell anemia (hemoglobin SS) and a comparison group of 26 black inner city schoolchildren without sickle cell disease or other known chronic illness. The youngsters with sickle cell anemia did not differ from a peer group of schoolchildren in personal, social, and total adjustments. The self-concept scores of the patient group were lower than those of the comparison group. An unexpected finding of the study was the observation that the anxiety scores (measuring acute anxiety) were significantly lower in the study group than those in the comparison group.