Main Complications during Pregnancy and Recommendations for Adequate Antenatal Care in Sickle Cell Disease: A Literature Review.

Sickle cell disease (SCD) is the most common monogenic disease worldwide, with a variable prevalence in each continent. A single nucleotide substitution leads to an amino-acid change in the ß-globin chain, altering the normal structure ofhemoglobin, which is then called hemoglobin S inherited in homozygosity (HbSS) or double heterozygosity (HbSC, HbSß), and leads to chronic hemolysis, vaso-occlusion, inflammation, and endothelium activation. Pregnant women with SCD are at a higher risk of developing maternal and perinatal complications. We performed a narrative review of the literature considering SCD and pregnancy, the main clinical and obstetrical complications, the specific antenatal care, and the follow-up for maternal and fetal surveillance. Pregnant women with SCD are at a higher risk of developing clinical and obstetric complications such as pain episodes, pulmonary complications, infections, thromboembolic events, preeclampsia, and maternal death. Their newborns are also at an increased risk of developing neonatal complications: fetal growth restriction, preterm birth, stillbirth. Severe complications can occur in patients of any genotype. We concluded that SCD is a high-risk condition that increases maternal and perinatal morbidity and mortality. A multidisciplinary approach during pregnancy and the postpartum period is key to adequately diagnose and treat complications.

Doença falciforme (DF) é a condição genética mais comum no mundo, com uma prevalência variável nos continentes. A substituição de um nucleotídeo muda um aminoácido na cadeia da ß globina, e altera a estrutura normal da hemoglobina, que é então chamada de hemoglobina S, e pode ser herdada em homozigose (HbSS) ou heterozigose (HbSC, HbSß), e leva a hemólise crônica, vaso-oclusão, inflamação, e ativação endotelial. Realizou-se uma revisão narrativa da literatura considerando doença falciforme e gestação, as complicações clínicas e obstétricas, o cuidado antenatal específico, e o seguimento para monitoramento materno e fetal. Gestantes com DF têm maior risco de desenvolver complicações clínicas e obstétricas, como crises dolorosas, complicações pulmonares, infecções, eventos tromboembólicos, pré-eclâmpsia, e morte materna. E seus recém-nascidos correm maior risco de desenvovler complicações neonatais: restrição de crescimento fetal, prematuridade e óbito fetal/neonatal. Complicações graves podem ocorrer em qualquer genótipo da doença. Concluiu-se que DF é uma condição de alto risco que aumenta a morbimortalidade materna e perinatal. Um seguimento com abordagem multidisciplinar na gestação e puerpério é fundamental para o diagnóstico e o tratamento das complicações.

Unusually High Prevalence of Stroke and Cerebral Vasculopathy in Hemoglobin SC Disease: A Retrospective Single Institution Study.

INTRODUCTION: Unlike homozygous hemoglobin SS (HbSS) disease, stroke is a rare complication in hemoglobin SC (HbSC) disease. However, recent studies have demonstrated a high prevalence of silent stroke in HbSC disease. The factors associated with stroke and cerebral vasculopathy in the HbSC population are unknown. METHODS: We conducted a retrospective study of all patients with sickle cell disease treated at the University of Missouri, Columbia, over an 18-year period (2000-2018). The goal of the study was to characterize the silent, overt stroke, and cerebral vasculopathy in HbSC patients and compare them to patients with HbSS and HbS/ß thalassemia1 (thal) in this cohort. We also analyzed the laboratory and clinical factors associated with stroke and cerebral vasculopathy in the HbSC population. RESULTS: Of the 34 HbSC individuals, we found that the overall prevalence of stroke and cerebral vasculopathy was 17.7%. Only females had evidence of stroke or cerebral vasculopathy in our HbSC cohort (33.3%, p = 0.019). Time-averaged means of maximum velocities were lower in the HbSC group than the HbSS group and did not correlate with stroke outcome. Among HbSC individuals, those with stroke and cerebral vasculopathy had a marginally higher serum creatinine than those without these complications (0.77 mg/dL vs. 0.88 mg/dL, p = 0.08). Stroke outcome was associated with recurrent vaso-occlusive pain crises (Rec VOCs) (75 vs. 25%, p = 0.003) in HbSC patients. The predominant cerebrovascular lesions in HbSC included microhemorrhages and leukoencephalopathy. CONCLUSION: There is a distinct subset of individuals with HbSC who developed overt, silent stroke, and cerebral vasculopathy. A female predominance and association with Rec VOCs were identified in our cohort; however, larger clinical trials are needed to identify and confirm specific clinical and laboratory markers associated with stroke and vasculopathy in HbSC disease.

Sickle cell retinopathy: characterization among patients over 40 years of age / Retinopatia falcêmica: caracterização da doença na população acima de 40 anos de idade

Abstract Purpose: This article aims to describe the prevalence of retinal alterations on the indirect binocular ophthalmoscopy exam in patients with sickle cell disease (HbSS or HbSC) who are over 40 years of age. Methods: This is a retrospective study in which patients with sickle cell disease (SCD) with an age group of 40 years or older were attended in a service of retina in Salvador, Brasil on the last 10 years. All patients were submitted to the clinical file filling, which includes the sociodemographic profile, clinical profile and ophthalmologic examination. The patients were divided in two groups (SS or SC), according to genotypic profile of hemoglobinopathy (HbSS or HbSC). The classification of retinopathy was performed according to Goldberg in proliferative and non-proliferative retinopathy. A P-value <0.05 was considered statistically significant. Results: A total of 97 patients (194 eyes) were evaluated, being 44 (45%) of the SC group and 53 (55%) of the SS group. Of the 97 patients, 19 (19.5%) did not present retinal changes and 78 (80,5%) present sickle cell retinopathy. Of the 78 patients with retinopathy, 22 (28%) had nonproliferative sickle retinopathy and 56 (72%) had proliferative alterations. The increase in vascular tortuosity was the most observed nonproliferative sign (26.8% of eyes) in both groups. The SC patients presented a greater proportion of findings of areas of retinal non perfusion (30%) than SS patients (p = 0.015). Conclusion: The results suggest the need for regular ophthalmologic follow-up of patients with SCD, especially in the older age group, due to the high prevalence of 80.5% of findings of sickle cell retinopathy on examination in patients over 40 years old.

Resumo Objetivos: Este artigo tem como objetivo avaliar a prevalência de alterações retinianas observadas pelo exame de oftalmoscopia binocular indireta em pacientes com doença falciforme (HbSS e HbSC) com mais de 40 anos de idade. Métodos: Estudo retrospectivo com pacientes com doença falciforme (DF) na faixa etária acima de 40 anos, atendidos em serviço especializado em Salvador, Brasil nos últimos 10 anos. Todos os pacientes foram submetidos ao preenchimento da ficha clínica, em que incluía perfil sociodemográfico, clínico e exame oftalmológico. Os pacientes foram divididos em dois grupos (SS ou SC), de acordo com seu padrão genotípico da hemoglobinopatia (HbSS ou HbSC). A classificação da retinopatia foi realizada de acordo com Goldberg em retinopatia não proliferativa e proliferativa. Um valor de p<0.05 foi considerado estatisticamente significante. Resultados: Um total de 97 pacientes (194 olhos) foram avaliados, sendo 44 (45%) do grupo SC e 53 (55%) do grupo SS. Dos 97 pacientes, 19 (19,5%) não apresentavam alterações retinianas e 78 (80,5%) apresentavam retinopatia falcêmica. Destes 78 pacientes com alterações retinianas, 22 (28%) possuem sinais de retinopatia não proliferativa e 56 (72%) possuem alterações proliferativas. O aumento da tortuosidade vascular foi o sinal de doença não proliferativa mais observado (26,8% dos olhos) em ambos os grupos. Os pacientes do grupo SC apresentaram a maior proporção de achados proliferativos, como áreas de não perfusão retiniana, que os pacientes SS (30%) (p = 0.015). Conclusão: Os resultados sugerem a necessidade de manter um acompanhamento oftalmológico regular dos pacientes com DF, especialmente pacientes com maior faixa etária, devido à alta prevalência observada (80,5%) de retinopatia falcêmica em pacientes acima de 40 anos de idade.

Polymorphisms in genes that affect the variation of lipid levels in a Brazilian pediatric population with sickle cell disease: rs662799 APOA5 and rs964184 ZPR1.

This cross-sectional study investigated associations between SNPs in metabolizing lipid genes, alpha-thalassemia and laboratory parameters in two forms of sickle cell disease (SCD), sickle cell anemia (SCA) and hemoglobin SC disease (HbSC) in a pediatric population. Among the groups SCA and HbSC was found a higher proportion of increased triglycerides (TG) in SCA. High levels of TG were significantly associated with lower hemoglobin (p = 0.006) and HDL-C (p = 0.037), higher white blood cell count (p = 0.027), LDH (p = 0.004) and bilirubins (p < 0.05) in SCD. Patients with HDL-C ≤40 mg/dL had higher markers hemolytic levels. Therapy of HU significantly influenced several hematological and biochemical parameters but not lipid fractions. Genotypes of the APOA5 rs662799 were not associated with lipid levels. The G-risk allele rs964184/ZPRI ZNF259/ZPR1 gene (GC + GG genotypes) was associated with increased levels of TG in children ≥10 years old (p = 0.045) and the atherogenic ratio TG/HDL-C (p = 0.032) in SCD. The use of HU improves levels of hemolysis and inflammation markers in SCD with high TG and, while not interfering with lipid levels, seems to overlap the effect of the G-risk allele in on them. This study reported for the first time that rs964184 SNP could be a genetic modifier of TG in SCD.

Clinical and hematological profile in a newborn cohort with hemoglobin SC / Perfil clínico e hematológico em uma coorte neonatal com hemoglobina SC

Abstract Objectives: Hemoglobin SC is the second most common variant of sickle-cell disease worldwide, after hemoglobin SS. The objectives of the study were to describe the clinical and laboratory characteristics of hemoglobin SC disease in children from a newborn screening program and treated at a blood center. Methodology: This study assessed a cohort of 461 infants born between 01/01/1999 and 12/31/2012 and followed-up until 12/31/2014. Clinical events were expressed as rates for 100 patient-years, with 95% confidence intervals. Kaplan-Meier survival curves were created. Results: The median age of patients was 9.2 years; 47.5% were female. Mean values of blood tests were: hemoglobin, 10.5 g/dL; reticulocytes, 3.4%; white blood cells, 11.24 × 109/L; platelets, 337.1 × 109/L; and fetal hemoglobin, 6.3%. Clinical events: acute splenic sequestration in 14.8%, blood transfusion 23.4%, overt stroke in 0.2%. The incidence of painful vaso-occlusive episodes was 51 (48.9-53.4) per 100 patient-years and that of infections, 62.2 episodes (59.8-64.8) per 100 patient-years. Transcranial Doppler ultrasonography (n = 71) was normal given the current reference values for SS patients. Hydroxyurea was given to ten children, all of whom improvement of painful crises. Retinopathy was observed in 20.3% of 59 children who underwent ophthalmoscopy. Avascular necrosis was detected in seven of 12 patients evaluated, predominantly in the left femur. Echocardiogram compatible with pulmonary hypertension was recorded in 4.6% of 130 children, with an estimated average systolic pulmonary artery pressure of 33.5 mmHg. The mortality rate from all causes was 4.3%. Conclusions: Clinical severity is variable in SC hemoglobinopathy. Several children have severe manifestations similar to those with SS disease.

Resumo Objetivos: A hemoglobinopatia SC é a segunda variante mais comum da doença falciforme no mundo, após a hemoglobinopatia SS. Os objetivos do estudo foram descrever as características clínicas e laboratoriais da hemoglobinopatia SC em recém-nascidos diagnosticados por programa de triagem neonatal e encaminhados para acompanhamento em hemocentro. Metodologia: Coorte de 461 recém-nascidos SC nascidos entre 01/01/1999 e 31/12/2012 e seguidos até 31/12/2014. A incidência de eventos clínicos foi expressa por taxas relativas a 100 pacientes-ano, com limites de confiança a 95%. Curvas de sobrevida foram construídas segundo Kaplan-Meier. Resultados: Mediana de idade, 9,2 anos; 47,5%, feminino. Médias dos valores hematológicos: hemoglobina 10,5 g/dL; reticulócitos 3,4%; leucometria 11,24 x 109/L; plaquetometria 337,1x109/L; hemoglobina fetal 6,3%. Eventos clínicos: sequestro esplênico agudo em 14,8%, hemotransfusão 23,4%, AVC isquêmico 0,2%. A incidência de episódios vaso-oclusivos dolorosos foi de 51 (48,9-53,4) por 100 pacientes-ano; a de infecções, 62,2 episódios (59,8-64,8) por 100 pacientes-ano. Doppler transcraniano (n = 71) foi normal, se usados os valores de referência de crianças SS. Dez pacientes usaram hidroxiureia, todos com melhoria das crises dolorosas. Retinopatia foi observada em 20,3% das 59 crianças que fizeram fundoscopia. Necrose avascular foi detectada em 7 de 12 pacientes avaliados, com predomínio no fêmur esquerdo. Ecocardiograma compatível com hipertensão pulmonar foi registrado em 4,6% de 130 crianças, com média estimada de 33,5 mm Hg de pressão arterial pulmonar. A taxa de mortalidade por todas as causas foi de 4,3%. Conclusões: A hemoglobinopatia SC tem gravidade variável; várias crianças apresentam manifestações clínicas intensas, semelhantes às da hemoglobinopatia SS.

Clinical and hematological profile in a newborn cohort with hemoglobin SC.

OBJECTIVES: Hemoglobin SC is the second most common variant of sickle-cell disease worldwide, after hemoglobin SS. The objectives of the study were to describe the clinical and laboratory characteristics of hemoglobin SC disease in children from a newborn screening program and treated at a blood center. METHODOLOGY: This study assessed a cohort of 461 infants born between 01/01/1999 and 12/31/2012 and followed-up until 12/31/2014. Clinical events were expressed as rates for 100 patient-years, with 95% confidence intervals. Kaplan-Meier survival curves were created. RESULTS: The median age of patients was 9.2 years; 47.5% were female. Mean values of blood tests were: hemoglobin, 10.5g/dL; reticulocytes, 3.4%; white blood cells, 11.24×109/L; platelets, 337.1×109/L; and fetal hemoglobin, 6.3%. Clinical events: acute splenic sequestration in 14.8%, blood transfusion 23.4%, overt stroke in 0.2%. The incidence of painful vaso-occlusive episodes was 51 (48.9-53.4) per 100 patient-years and that of infections, 62.2 episodes (59.8-64.8) per 100 patient-years. Transcranial Doppler ultrasonography (n=71) was normal given the current reference values for SS patients. Hydroxyurea was given to ten children, all of whom improvement of painful crises. Retinopathy was observed in 20.3% of 59 children who underwent ophthalmoscopy. Avascular necrosis was detected in seven of 12 patients evaluated, predominantly in the left femur. Echocardiogram compatible with pulmonary hypertension was recorded in 4.6% of 130 children, with an estimated average systolic pulmonary artery pressure of 33.5mmHg. The mortality rate from all causes was 4.3%. CONCLUSIONS: Clinical severity is variable in SC hemoglobinopathy. Several children have severe manifestations similar to those with SS disease.

Velocidade de fluxo sanguíneo cerebral em crianças em crianças e adolescentes com doença falciforme em Salvador, Bahia / Cerebral blood flow velocity in children and adolescents with sickle cell disease in Salvador, Bahia

INTRODUÇÃO: A doença falciforme (DF) é caracterizada por complicações agudas e crônicas. Entre as agudas podemos citar: episódios álgicos, síndrome torácica aguda (STA), priapismo, crise hemolítica, infecções agudas e acidente vascular cerebral (AVC), sendo este útimo responsavel por complicações a longo prazo na infância. A velocidade do fluxo sanguíneo cerebral (VFSC) elevada é o fator de risco mais importante para o desenvolvimento do AVC em crianças com anemia falciforme. A identificação de pacientes de risco associados a velocidades de fluxo sanguíneos cerebrais anormais é realizada pelo Doppler transcraniano (DTC), exame fundamental à prevenção primária do AVC. OBJETIVOS: Avaliar as velocidades de fluxo sanguíneo cerebral em crianças e adolescentes com DF em Salvador-Bahia, para identificar aqueles com risco alto de AVC, além de correlacionar as velocidades de fluxo cerebral com os perfis clínico e hematológico dos pacientes. PACIENTES E MÉTODOS: O DTC por insonação, utilizando uma sonda de 2 MHZ...

BACKGROUND: Sickle cell disease (SCD) is characterized by acute episodes of illnesses (crises) such as bone pain crisis, acute chest syndrome (ACS), priapism, hemolytic crisis, acute infections; and acute and long term complications such as cerebrovascular accident (CVA). Abnormally high cerebral blood flow velocity is the most important risk factor for development of stroke in pediatric patients with sickle cell anemia, and its detection by transcranial Doppler (TCD) is fundamental in primary stroke prevention. Other clinical, hematologic and genetic risk factors of stroke have also been identified. OBJECTIVES: The study aimed at evaluating the cerebral blood flow velocities of children and adolescents with SCD in Salvador, Brazil, detect those at high risk of stroke and correlate the flow velocities with clinical and hematological profiles of the patients. PATIENTS AND METHODS: Transcranial Doppler was performed on subjects aged 2 to 16 years who fulfilled the inclusion criteria, using a 2 MHz...

Kidney Disease among Patients with Sickle Cell Disease, Hemoglobin SS and SC.

BACKGROUND AND OBJECTIVES: Sickle cell disease (SCD) is an inherited anemia that afflicts millions worldwide. Kidney disease is a major contributor to its morbidity and mortality. We examined contemporary and historical SCD populations to understand how renal disease behaved in hemoglobin SS (HbSS) compared with HbSC. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Kidney function was examined in the multicentered Treatment of Pulmonary Hypertension and Sickle Cell Disease with Sildenafil Therapy (Walk-PHaSST) Trial (HbSS=463; HbSC=127; years 2007-2009) and historical comparator populations from the Cooperative Study of Sickle Cell Disease (CSSCD; HbSS=708) and the Multicenter Study of Hydroxyurea in Sickle Cell Disease (MSH; HbSS=299). RESULTS: In adults with SCD, eGFR was lower among older individuals: -1.78 ml/min per 1.73 m(2) per year of age (95% confidence interval [95% CI], -2.06 to -1.50; Walk-PHaSST Trial), -1.75 ml/min per 1.73 m(2) per year of age (95% CI, -2.05 to -1.44; MSH), and -1.69 ml/min per 1.73 m(2) per year of age (95% CI, -2.00 to -1.38; CSSCD) in HbSS compared with -1.09 ml/min per 1.73 m(2) per year of age (95% CI, -1.39 to -0.75) in HbSC (Walk-PHaSST Trial). Macroalbuminuria was seen in 20% of participants with SCD (HbSS or HbSC; P=0.45; Walk-PHaSST Trial), but microalbuminuria was more prevalent in HbSS (44% versus 23% in HbSC; P<0.002). In the Walk-PHaSST Trial, albuminuria was associated with hemolysis (higher lactate dehydrogenase, P<0.001; higher absolute reticulocyte count, P<0.02; and lower Hb, P=0.07) and elevated systolic BP (P<0.001) in HbSS. One half of all participants with HbSS (20 of 39) versus one fifth without (41 of 228) elevated tricuspid regurgitant jet velocity (≥3 m/s; adverse prognostic indicator in SCD) had macroalbuminuria (P<0.001). In the CSSCD, overt proteinuria, detected (less sensitively) by urine dipstick, associated with higher 3-year mortality (odds ratio, 2.48; 95% CI, 1.07 to 5.77). Serum bicarbonate was lower in HbSS (23.8 versus 24.8 mEq/dl in HbSC; P<0.05) and associated with reticulocytopenic anemia and decreased renal function. CONCLUSIONS: In SCD, albuminuria or proteinuria was highly prevalent, in HbSS more than in HbSC. Proteinuria associated with mortality in HbSS. Older individuals had a lower than expected eGFR, and this was more prominent in HbSS. Current management does not routinely address renal complications in SCD, which could plausibly reduce morbidity and mortality.

Chronic kidney disease is common in sickle cell disease: a cross-sectional study in the Tema Metropolis, Ghana.

BACKGROUND: Renal involvement in sickle cell disease (SCD) contributes significantly to morbidity and mortality. The aim of this study was to determine the prevalence of chronic kidney disease (CKD) amongst SCD patients, and how basic clinical variables differ across haemoglobin genotypes. METHODS: A hospital-based cross-sectional study conducted from December 2013 to May 2014 at the Sickle cell clinic of the Tema General Hospital. One hundred and ninety-four (194) participants with SCD, receiving medical care at the outpatient sickle cell clinic were enrolled onto the study. A structured questionnaire was administered to obtain information on demography, clinical history, blood pressure and anthropometry. Blood and urine samples were taken for serum creatinine and proteinuria determination respectively. The estimated GFR (eGFR) was calculated using the CKD-EPI and Schwartz equations. CKD was defined according to the Kidney Disease Improving Global Outcomes (KDIGO) guidelines. Analysis was performed using GraphPad prism and P <0.05 was considered statistically significant. RESULTS: CKD was present in 39.2% of participants. Using KDIGO guidelines, 40.8% of the HbSS participants had stage 1 CKD and none had stage 2 CKD. In addition, 30.8% of the HbSC participants had stage 1 CKD and 3.8% had stage 2 CKD. There was a trend of increasing age across CKD stages and stage 2 CKD participants were oldest (P < 0.001). CONCLUSION: Results from the current study suggest that CKD is common amongst SCD patients and prevalence and intensity increases with age. Proteinuria and CKD was more common in HbSS genotype than in HbSC genotype.

The clinical significance of K-Cl cotransport activity in red cells of patients with HbSC disease.

HbSC disease is the second commonest form of sickle cell disease, with poorly understood pathophysiology and few treatments. We studied the role of K-Cl cotransport activity in determining clinical and laboratory features, and investigated its potential role as a biomarker. Samples were collected from 110 patients with HbSC disease and 41 with sickle cell anemia (HbSS). K-Cl cotransport activity was measured in the oxygenated (K-Cl cotransport(100)) and deoxygenated (K-Cl cotransport(0)) states, using radioactive tracer studies. K-Cl cotransport activity was high in HbSC and decreased significantly on deoxygenation. K-Cl cotransport activity correlated significantly and positively with the formation of sickle cells. On multiple regression analysis, K-Cl cotransport increased significantly and independently with increasing reticulocyte count and age. K-Cl cotransport activity was increased in patients who attended hospital with acute pain in 2011 compared to those who did not (K-Cl cotransport(100): mean 3.87 versus 3.20, P=0.009, independent samples T-test; K-Cl cotransport(0): mean 0.96 versus 0.68, P=0.037). On logistic regression only K-Cl cotransport was associated with hospital attendance. Increased K-Cl cotransport activity was associated with the presence of retinopathy, but this effect was confounded by age. This study links variability in a fundamental aspect of cellular pathology with a clinical outcome, suggesting that K-Cl cotransport is central to the pathology of HbSC disease. Increased K-Cl cotransport activity is associated with increasing age, which may be of pathophysiological significance. Effective inhibition of K-Cl cotransport activity is likely to be of therapeutic benefit.

Blood typing profile of a school-aged population of a North Togo township.

The aim of this study was the determination of hemoglobin (Hb) variants and ABO blood groups in a school population aged 6 to 9 years in the township of Agbandé-Yaka in North Togo. A cross-sectional study was carried out on 570 children of four primary schools at Agbande-Yaka, between March and July 2010. Hemoglobin characterization was done by alkaline buffer electrophoresis and the blood types ABO-Rhesus (Rh) D by immuno-hematological methods. A Hb variant was detected in 37.0% of the schoolchildren. Among them, the AS trait accounted for 11.9% and the AC trait for 20.2%. Homozygous Hb S (HBB: c.20A>T) was not found but Hb C (HBB: c.19G>A) appeared at a frequency of 3.3%, while compound heterozygotes carrying Hb SC were seen at a frequency of 1.6%. The O, B and A blood groups accounted for 49.0, 26.8 and 21.9%, respectively. The Hb anomalies reached a high prevalence in this school population. These results are remarkable by the absence of homozygous Hb S individuals compared to homozygous Hb C individuals, which were as numerous as expected. The frequencies of the ABO blood groups are similar to what has been found in other West African populations.

Impact of sickle hemoglobinopathies on pregnancy-related venous thromboembolism.

OBJECTIVE: The aim of the study is to examine the relationship between sickle cell trait (Hb AS) and other sickle hemoglobinopathies and the risk of thromboembolism during pregnancy or the puerperium. STUDY DESIGN: Retrospective cohort study of African American women receiving prenatal care from 1991 to 2006. Sickle cell status was ascertained by routine hemoglobin electrophoresis. Venous thromboembolism (VTE) was defined as one or more episodes of deep venous and/or pulmonary thromboembolism during pregnancy or the puerperium according to discharge diagnoses based on International Classification of Diseases, Ninth Revision codes. RESULTS: Among 22,140 women with hemoglobin (Hb) AA status, 20 women (0.09%) experienced pregnancy-related VTE compared with 3 women (0.15%) of 2,037 women with Hb AS; relative risk (RR) for the association with AS status = 1.6; 95% confidence interval (CI) 0.5 to 5.5. Of 103 women, 3 women (2.9%) with sickle cell disease conditions (Hb SS, Hb SC, or Hb S,beta-thalassemia) experienced thromboembolism. Compared with women with Hb AA status, the RR = 32.2, 95% CI 9.7 to 107. CONCLUSION: Sickle cell trait may be associated with a modest increase in VTE in the setting of pregnancy; sickle cell disease conditions are strongly associated with this rare but potentially fatal outcome.

Sickle cell retinopathy: diagnosis and treatment.

Hemoglobinopathies are a group of inherited disorders characterized by quantitative or qualitative malformations of hemoglobin (Hb). Some of these diseases present vaso-occlusive phenomena that are responsible for high morbidity in clinical and/or ophthalmologic terms. Diagnosis of hemoglobinopathies is performed exclusively through hemoglobin electrophoresis. From the ophthalmologic perspective, the most important representative of this group of diseases is sickle cell retinopathy, which presents a wide spectrum of fundus manifestations and may even lead to irreversible vision loss if not properly diagnosed and treated. The aim of this review is to present the classification of sickle cell retinopathy and to describe current management and future perspectives for its treatment, taking into consideration the clinical management of these patients.

Sickle cell retinopathy: diagnosis and treatment / Retinopatia falciforme: diagnóstico e tratamento

Hemoglobinopathies are a group of inherited disorders characterized by quantitative or qualitative malformations of hemoglobin (Hb). Some of these diseases present vaso-occlusive phenomena that are responsible for high morbidity in clinical and/or ophthalmologic terms. Diagnosis of hemoglobinopathies is performed exclusively through hemoglobin electrophoresis. From the ophthalmologic perspective, the most important representative of this group of diseases is sickle cell retinopathy, which presents a wide spectrum of fundus manifestations and may even lead to irreversible vision loss if not properly diagnosed and treated. The aim of this review is to present the classification of sickle cell retinopathy and to describe current management and future perspectives for its treatment, taking into consideration the clinical management of these patients.

As hemoglobinopatias são um grupo de doenças hereditárias caracterizadas por mal-formações quantitativas ou qualitativas da hemoglobina (Hb). Algumas destas doenças podem apresentar fenômenos vaso-oclusivos, responsáveis por alta morbidade do ponto de vista clínico e/ou oftalmológico. O diagnóstico das hemoglobinopatias é feito exclusivamente através da eletroforese de hemoglobinas. Do ponto de vista oftalmológico, a representante mais importante deste grupo de doenças é a retinopatia falciforme, que pode apresentar um amplo espectro de manifestações fundoscópicas, podendo, inclusive, levar à perda visual irreversível se não for corretamente diagnosticada e tratada. O objetivo desta revisão é apresentar a classificação desta doença, a conduta no tratamento atual, bem como suas perspectivas futuras de tratamento, considerando-se as particularidades no manejo clínico destes pacientes.

Adverse neurological outcomes in Nigerian children with sickle cell disease.

Sickle cell disease (SCD) is reported to be the most common genetic disorder affecting Nigerians. Children with SCD are at a high risk of neurological morbidity. The main objective of this study was to determine the pattern of adverse neurological outcomes among a cohort of Nigerian children with SCD. All children with SCD seen in the Department of Paediatrics, University College Hospital, Ibadan, Nigeria, over a period of 2 years were carefully evaluated for symptoms and signs of neurological complications, defined as clinical outcomes referable to the central nervous system. Of the 214 children evaluated, 187 were diagnosed with Hb SS disease and 27 with Hb SC disease. Neurological complications were identified in 78 (36.4 %) of the cases. The most common complications were headache (17.8 %), seizure (9.3 %) and stroke (8.4 %). Other less frequent complications included bacterial meningitis (2.8 %), spontaneous visual loss (1.4 %), paraplegia (0.9 %) and transient ischaemic attacks (0.9 %). Neurological complications occurred more frequently in children with sickle cell anaemia than in those with Hb SC disease (P = 0.002, 95 % CI 1.450-82.870). Adverse neurological events are common in Nigerian children with SCD, with a significantly higher risk in Hb SS than Hb SC disease. Stroke represents a major underlying cause of symptomatic epilepsy in SCD. Institution of primary preventive measures for stroke in SCD will significantly reduce the burden of stroke and epilepsy associated with SCD in Nigeria.

Sickle cell disease does not predispose to caries or periodontal disease.

This study investigated the prevalence of dental caries and periodontal condition in a population with sickle cell disease (SCD), analyzing some associations with disease severity. The Decayed, Missing and Filled Teeth index (DMFT) and Community Periodontal Index (CPI) were recorded for 99 individuals with SCD and 91 matched controls. Socio-demographic status, oral health behaviors, and history of clinical severity of SCD were assessed. Statistical comparisons were performed between the group with SCD and the control group, as well as multivariate logistic regression analyses with DMFT index and CPI as the dependent variables. The mean number of decayed teeth was significantly higher in individuals with HbSS. Older age, female gender, and daily smoking were identified as risk factors for higher DMFT, while older age and absence of daily use of dental floss were risk factors for the development of periodontal disease. In conclusion, risk factors known to cause caries and periodontal disease had more influence on oral health than the direct impact of SCD.

Acute chest syndrome is associated with history of asthma in hemoglobin SC disease.

BACKGROUND: Acute chest syndrome (ACS) is a frequent cause of morbidity and leading cause of death among individuals with sickle cell disease. Yet, ACS in hemoglobin SC disease is not well characterized. The objective of this study was to compare the presentation and clinical course of ACS in individuals with hemoglobin SC disease to that observed in individuals with hemoglobin SS disease. PROCEDURE: We retrospectively reviewed 71 inpatient episodes of ACS in patients with hemoglobin SC disease over a 20-year period. Continuous and categorical data from index cases were compared with that from 71 control cases of ACS in patients with hemoglobin SS disease. RESULTS: Median length of hospitalization was shorter for hemoglobin SC episodes when compared to hemoglobin SS episodes (3.0 vs. 5.0 days, P < 0.001). In comparison to hemoglobin SS patients, a greater proportion of hemoglobin SC patients had a previous history of asthma or wheezing (50.7 vs. 33.8%, OR = 2.01 [1.02-3.96], P = 0.041) and a respiratory complaint of wheeze (11.3 vs. 2.8%, OR = 4.38 [0.90-21.4], P = 0.049). In our multivariate regression model, time to ACS diagnosis and total number of days of oxygen supplementation were independent predictors of length of hospitalization in both hemoglobin SC and SS episodes of ACS. CONCLUSIONS: ACS appears to be less severe in children with hemoglobin SC disease compared to that in children with SS disease. Asthma and wheezing may represent more significant risk factors for the development of ACS in children with hemoglobin SC disease.

Co–herencia de poliquistosis renal autosómica dominante y hemoglobina con rasgo falciforme en afroamericanos / Co–inheritance of autosomal dominant polycystic kidney disease and sickle cell trait in African Americans

Antecedentes: La hematuria macroscópica derivada de la rotura de quistes renales es una manifestación habitual en la poliquistosis renal autosómica dominante (PQRAD). La enfermedad por células falciformes es una anomalía de la hemoglobina, que se hereda con carácter autosómico recesivo, consistente en la sustitución de la valina por el ácido glutámico en la posición 6 del gen de la 3–globina en el brazo corto del cromosoma 11. La gravedad de la enfermedad es proporcional a la cantidad de hemoglobina S (Hb S) en los hematíes: los heterocigotos con hemoglobina con rasgo falciforme (Hb S <50%) y los homocigotos con enfermedad por células falciformes (Hb S >75%). La presencia de hemoglobina con rasgo falciforme (Hb AS) se acompaña de manifestaciones renales, especialmente hematuria, y la necrosis papilar es la causa más frecuente de hematuria macroscópica en los pacientes heterocigotos portadores de esta hemoglobinopatía. La asociación de estas dos enfermedades hereditarias, PQRAD y hemoglobina con rasgo falciforme, se ha comunicado raramente. Se ha sugerido que los pacientes con PQRAD y hemoglobina con rasgo falciforme podían desarrollar precozmente insuficiencia renal crónica (IRC). Recientemente, se ha comunicado que la hemoglobina con rasgo falciforme es un factor de riesgo predisponente para el desarrollo de enfermedad renal crónica en afroamericanos. Pacientes y métodos: Se estudiaron 2 familias de origen afroamericano (4 pacientes) que co–heredaron la PQRAD y la hemoglobina con rasgo falciforme (heterocigotos). El diagnóstico de hemoglobina falciforme (Hb S) se realizó por electroforesis de la hemoglobina. El volumen renal se midió mediante resonancia magnética (RM). Resultados: La paciente índice, perteneciente a una de las familias, presentó episodios de hematuria macroscópica recidivantes, asociados (..) (AU)

Background: Macroscopic haematuria secondary to renal cyst rupture is a frequent complication in autosomal dominant polycystic kidney disease (ADPKD). Sickle–cell disease is an autosomal recessive haemoglobinopathy that involves a qualitative anomaly of haemoglobin due to substitution of valine for the glutamic acid in the sixth position of 3–globin gene on the short arm of chromosome 11. For the full disease to be manifested, this mutation must be present on both inherited alleles. The severity of the disease is proportional to the quantity of haemoglobin S (Hb S) in the red cells; sickle–cell trait (Hb S <50%) and homozygous sickle–cell disease (Hb S >75%). In sickle–cell disease, the abnormal Hb S loses its rheological characteristics and is responsible of the various systemic manifestations including those of the kidney, such as macroscopic haematuria secondary to papilar necrosis. Despite the generally benign nature of the sickle–cell trait, several potentially serious complications have been described. Metabolic or environmental changes such as hypoxia, acidosis, dehydration, hyperosmolality or hyperthermia may transform silent sickle–cell trait into a syndrome resembling sickle–cell disease with vaso–occlusive crisis due to an accumulation of low deformable red blood cells in the microcirculation originating haematuria from papilar necrosis. On the other hand, it has been demonstrated an earlier onset of end–stage renal disease (ESRD), in blacks with ADPKD and sickle–cell trait when compared with blacks with ADPKD without the trait. Patients and methods: We studied 2 african–american families (4 patients) which presented with both ADPKD and sickle–cell trait (Hb S <50%). The diagnosis of sickle–cell trait was confirmed by haemoglobin electrophoresis. The renal volume was measured by magnetic resonance imaging (..) (AU)

Polysomnographic characteristics of a referred sample of children with sickle cell disease.

STUDY OBJECTIVES: To describe polysomnographic parameters and their clinical correlates in a referred sample of children with sickle cell disease (SCD). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Hearing impairment in persons with the hemoglobin SC genotype.

The hemoglobin (Hb) SC genotype is seen in persons who have inherited the gene for hemoglobin S from one parent and the gene for hemoglobin C from the other. Some people with this genotype develop Hb SC disease, a variant of sickle cell disease. Hb SC disease, a compound heterozygous condition, is the most common of the hemoglobinopathies and the least severe, although it is still serious. One of the documented complications of the presence of the Hb SC genotype is sensorineural hearing loss (SNHL). We conducted a prospective case-control study of 43 subjects, aged 15 to 65 years, who had the Hb SC genotype to determine the incidence of SNHL and to determine if the hearing loss in these subjects was correlated with sex or age. Our control group was made up of 100 generally healthy, sex- and age-matched subjects with the normal Hb AA genotype. SNHL was defined as a loss of more than 25 dB HL at two or more frequencies in the same ear or at one or more frequencies in both ears. We found that SNHL was present in 12 of the 43 subjects (27.9%) in the Hb SC group (17 of 86 ears [19.8%]) and in 17 of the 100 subjects (17.0%) in the Hb AA group (21 of 200 ears [10.5%]; the difference between the two groups was not statistically significant (chi(2) = 1.589; p = 0.105). We found that in the Hb SC group, SNHL was more common among females than males (38.5 vs. 11.8%), although the difference was not quite significant statistically (chi(2) = 2.435; p = 0.056); in the Hb AA group, the incidence was fairly equal-15.4 and 18.8%, respectively (chi(2) = 0.033; p = 0.427). Therefore, we conclude that the hearing loss in the subjects of this study was not correlated with the presence of the Hb SC genotype in either sex. In terms of age, SNHL was significantly more common in subjects aged 41 to 65 years than in those aged 15 to 40 years in both genotype groups. In the Hb SC group, SNHL was present in 4 of the 33 younger subjects (12.1%) and in 8 of the 10 older subjects (80.0%) (chi(2) = 14.354; p < 0.001). In the Hb AA group, the corresponding figures were 7 of 85 (8.2%) and 10 of 15 (66.7%) (chi(2) = 26.840; p < 0.001). Therefore, we conclude that the hearing loss in the subjects of this study was a function of age and was not associated with the presence of the Hb SC genotype.