ARTIGO ORIGINAL

ORIGINAL ARTICLE


Estado nutricional e indicadores bioquímicos de adultos com anemia falciforme

Nutritional status and biochemical indicators of adults with sickle cell anemia admitted to an emergency service

  • Recebido: 04 de Julho de 2017
  • Aprovado: 23 de Novembro de 2017
  • Publicado: 13 de Julho de 2018
  • Atualidades Médicas - Volume 1 - Edição nº 4 - Ano 2017 - Novembro, Dezembro
  • Páginas: 142-148
  • DOI:

© Copyright MRCOM. Todos os direitos reservados.

Resumo

A anemia falciforme (AF) é um problema de saúde pública mundial. Pouco tem sido descrito sobre o estado nutricional de adultos com AF, principalmente das condições nutricionais dos pacientes que são mais frequentemente hospitalizados. Objetivo: Comparar, em dois períodos distintos, o estado nutricional e os indicadores bioquímicos de adultos com AF, frequentemente admitido em serviço de emergência. Métodos: Estudo descritivo dos adultos com anemia falciforme admitidos (semanal ou mensal) no serviço de emergência de um hospital de hematologia nos anos 2008 e 2010. Foram analisados peso, altura, albumina, globulina, hemoglobina, contagem de reticulócitos, ferritina, sódio, potássio, gamaglutamil-transferase (GGT), fosfatase alcalina (ALP), aspartato aminotransferase (AST), alanina aminotransferase (ALT), ureia, creatinina, ácido úrico, lactato desidrogenase (LDH) e de hemoglobina fetal. Resultados: Foram avaliados 42 adultos (26 homens), com idade média de 28 (21 ± 42) anos para homens e 32 (20 ± 50) anos para as mulheres. Todos foram internados por crises álgicas. Em ambos os sexos, houve predomínio de eutrofia nos dois anos analisados. Os resultados dos testes bioquímicos foram comparados entre 2008 e 2010, mostrando que os homens tiveram mudanças significantes nos valores de LDH, creatinina, ALT e bilirrubina direta; mulheres apresentaram mudança na AST. Conclusão: Em ambos os anos predominou a eutrofia, independentemente do sexo e a desnutrição estava presente apenas nos homens (11,9%). Os homens apresentaram alterações bioquímicas de piora da função renal e hemólise, condições que comprometem o estado nutricional.

Summary

Sickle cell anemia (SCA) is a worldwide public health problem. Little has been described about the nutritional status of adults with SCA and the nutritional conditions of patients that are more often hospitalized remain unknown. Objective: To compare, in two different periods, the nutritional status and biochemical indicators of adults with SCA often admitted in an emergency service. Methods: A descriptive study of adults with sickle cell anemia admitted (weekly or monthly) in the emergency service of a hematology hospital in years 2008 and 2010. Data on weight, height, albumin, globulin, hemoglobin, reticulocyte count, ferritin, sodium, potassium, gammaglutamil transferase (GGT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, creatinine, uric acid, lactate dehydrogenase (LDH) and fetal hemoglobin were collected. Results: We evaluated 42 adults (26 men), with mean age 28 (21 ± 42) years for men and 32 (20 ± 50) years for women. All of them were admitted due to painful crises. In both gender, there was predominance of normal weight in the two years analyzed. Comparison of 2008 and 2010 biochemical tests showed that men had significant changes in LDH, creatinine, ALT, and direct bilirubin values; women had changes in AST. Conclusion: In both years normal weight predominated regardless of sex, and malnutrition was present only in men (11.9%). Men showed biochemical changes of worsening renal function and hemolysis, conditions that compromise the nutritional status.

Unitermos/Uniterms

  • anemia falciforme
  • nutrição
  • estado nutricional
  • índice de massa corporal
  • hemoglobina
  • sickle cell anemia
  • nutrition
  • nutritional status
  • body mass index
  • hemoglobin

Introduction

According to the World Health Organization (WHO), 7% of the world population has hemoglobinopathies and in some regions the frequency of gene carriers reaches is 25%.1 Hemoglobinopathies include sickle cell disease and thalassemia, and sickle cell disease accounts for 70% of cases1. Sickle cell anemia (SCA) is the most common group of genetic disorder in the world.2,3,4

The most common clinical manifestations in patients with SCA are acute painful crises6,7, acute chest syndrome8 and bacterial infections9 which entail numerous hospitalizations, and increased morbidity and mortality10. In Brazil, a study conducted by Loureiro et al11 stated that 78.6% of deaths were due to the disease and occured up to 29 years old, and 37.5% of these were in children under nine years old. The high fatality rate, affecting mainly young people, reflects the severity of the disease8 and explains the concentration of studies on children12.

Vaso-occlusive events result in tissue ischemia leadind to acute and chronic pain as well as organ damage that can affect any organ in the body including the bones, lungs, liver, kidneys, brain, eyes and joints. 32

Frequently, the presence of fever, painful crisis, hypermetabolism and other morbidities, favors the emergence and/or aggravation of malnutrition, a condition recently described as common in these patients14. Studies show the importance of nutritional monitoring of these patients, because of reduced levels of some important micronutrients15,16. The absence of adequate nutritional monitoring and the unawareness of the disease by health professionals contribute to malnutrition, with consequent worse prognosis. The effects of malnutrition on the development of hospitalized patients reported as contributing factors in mortality and morbidity. Few studies that describe the nutritional status and biochemical indicators of adults with sickle cell disease.

This study aims to compare, in two different periods, the nutritional status and biochemical indicators of adults with sickle cell anemia frequently admitted in an emergency service.

Methods

Study design

This is a descriptive retrospective study conducted in adults with sickle cell anemia (SCA) followed at the Emergency Service of Siqueira Cavalcanti Hematology Institute (Hemorio) in 2008 and 2010.

Inclusion criteria

Patients were included if they had SCA; were between the ages of 20 to 50 years; have had weekly or monthly admissions in Hemorio's emergency in 2008 and 2010; agreed to participate in the study and signed the consent form and are lucid and oriented on admission.

Patients

In 2008, 234 SCA patients were treated in Hemorio's emergency. There were sample losses due to misdiagnosis of the SS genotype (10 patients); lack of registration of weight or height on medical records in 2008 (90 patients); not meeting the age criteria (80 patients) and death (12 patients). Thus 42 patients remained. Data from this group were collected from medical records in 2008, and obtained sometime in 2010, during hospitalization.

Clinical diagnosis and nutrition

The assessment of nutritional status utilized anthropometric and biochemical parameters. The body mass index (BMI) was determined according to the WHO (1997).

Biochemical and hematological parameters were assessed including hemoglobin, reticulocytes count, fetal hemoglobin, total serum protein and albumin, ferritin, sodium, potassium, gamma glutamil transferase (GGT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, creatinine, uric acid and lactate dehydrogenase (LDH).

Reading the medical records was also observed whether there was the use of some sort of nutritional supplementation.

Analysis Plan

The data were analyzed using the program Sigma Star®, version 3.5. The results were expressed as mean ± standard deviation or median (minimum value found - maximum value). Applied tests the Fisher exact test and the X2 test to analyze the frequency of cases in different years, while for analyzing the difference between two independent variables, the Student t test or Mann-Whitney. For the correlation analysis was conducted the test of Pearson. The statistic calculation was maker using significance p< 0.05.

Ethical Aspects

This study was conducted in accordance with the ethical standards outlined for research in humans in the Declaration of Helsinki, and approved by the Research Ethics Committee of the Clinical Research Siqueira Cavalcanti Hematology Institute (nº 210/10). All patients who agreed to participate in the study signed an informed consent form.

Results

Forty-two adults with SCA (26 men) with aged 30 ± 6.7 years were the subject of this study. Painful crisis was the reason for hospitalization in the emergence of all patients. Not been consumed by any patient nutritional supplements. BMI classification, in both years, revealed predominance of eutrophic both gender and malnutrition was present in 11.9% of the patients (Table 1). In 2008 there was no statistical difference in BMI between men and women (p=0.16). Women had higher BMI values and men (n=5) had with malnutrition in both years (Table 1). In 2010, the Pearson correlation analysis revealed that the levels of Hb (r= 0.39; p <0.02) tend to increase together BMI.

Table 1. Body mass index (BMI) and BMI classification of men and women with sickle cell anemia admitted to an emergency service in 2008 and 2010.

2008 2010
BMI (kg/m2) 21.29 ± 3.16 21.23 ± 2.73
Men 20.79 ± 2.97 20.56 ± 2.25
Women 22.09 ± 3.38 22.29 ± 3.15
BMI Classification
Mild malnutrition 05 (11.90%) 05 (11.90%)
Eutrophy 33 (78.60%) 35 (83.30%)
Overweight 03 (7.10%) 01 (2.40%)
Obesity grade I 01 (2.40%) 01 (2.40%)

Laboratory tests revealed that serum albumin was normal, hemoglobin levels were low and LDH levels increased in 2008 and 2010 (Table 2). A comparison of results from 2008 and 2010 of men and women was taken separately. In men, there was a significant increase in creatinine (p=0.04), ALT ( (p=0.41) and direct bilirubin (p=0.22). In women we noticed significant increase in AST (P=0.55) (Table 2).

Table 2. Media (DP) of results of biochemical parameters of men and women with sickle cell anemia in 2008 and 2010

Biochemical indicators Men (n=26) p value and Test Women (n=16) p value and Test
2008 2010 2008 2010
Total protein, g/dl 8.26 (0.44) 7.97 (1.06) 0.48* 7.99 (0.68) 8.42 (0.47) 0.11*
Albumin, g/dl 4.30 (0.80) 4.28 (0.37) 0.96 4.30 (0.66) 4.57 (0.34) 0.24*
Globulin, g/dl 3.95 (0.61) 3.68 (1.08) 0.63 3.69 (0.66) 3.84 (0.49) 0.55*
Ferritin, ng/ml 1026.57 (842.55) 866.45 (875.89) 0.72* 3846.00 (4820.13) 2063.40 (1327.35) 0.30*
Hemoglobin,g/dl 9.42 (1.68) 8.80 (1.57) 0.34* 8.08 (1.68) 8.29 (1.91) 0.76*
Reticulocytes, % 354.05 (139.85) 319.96 (134.00) 0.45* 318.98 (124.19) 278.72 (168.18) 0.47*
Urea, mg/dl 25.46 (36.44) 26.65 (28.73) 0.42 18.73 (9.06) 25.44 (20.47) 0.54
Uric acid, mg/dl 5,55 (1.76) 5.19 (2.15) 0.52* 4.54 (1.38) 4.65 (1.45) 0.84*
Creatinin, mg/dl 0.75 (0.51) 0.93 (0.30) 0.001 0.72 (0.32) 0.86 (0.33) 0.24*
Sodium, mEq/L 138.81 (2.97) 139.34 (3.79) 0.57* 138.86 (1.95) 139.37 (2.16) 0.50*
Potassium, mEq/L 4.26 (0.49) 4.11 (0.35) 0.21* 4.27 (0.56) 4.21 ( 0.51) 0.74*
Fetal hemoglobin, % 4.37 (0.04) 4.55 (0.05) 0.70 4.95 (4.75) 2.95 (2.62) 0.29
LDH, UI/L 779.92 (479.75) 1058.46 (659.44) 0.05 760.86 (452.82) 807.68 (491.15) 0.85
AST, U/l 62.46 (30.39) 51.04 (22.62) 0.19 60.66 (28.91) 49.81 (44.43) 0.04
ALT, U/l 45.57 (20.62) 37.88 (43.38) 0.006 36.8 (22.70) 29.94 (27.54) 0.11
GGT, U/l 136.87 (94.74) 104.18 (67.48) 0.22* 130.87 ± 61.81 213.07 (214.30) 0.31*
Direct bilirubin, mg/dl 1.16 (1.78) 2.76 (7.75) 0.04 0.58 ± 0.25 14.89 (55.50) 0.07
Indirect bilirubin, mg/dl 2.52 (1.78) 3.07 (4.72) 0.64 8.42 (27.83) 2.38 (4.80) 0.43
Alkaline phosphatase, U/l 144.25 (91.22) 136.95 (55.56) 0.62 137.1 (68.5)
    1. (159.9
0.42

* T Test; †Mann-Whitney Test.

Discussion

The main results of this study were: (a) eutrophic predominated in 2008 and 2010 in both gender; (b) all patients had painful crises in admission; (c) between the years 2008 and 2010, the group of men showed a significant increase in LDH, creatinine, ALT and direct bilirubin values and in the group of women the increase was in AST.

The choice to study the nutritional status of adults with SCA was due to the severity of their clinical condition, which causes frequent hospitalizations19 and not described in the literature nutritional status of individuals with sickle cell disease that most often admitted in emergency. A retrospective study conducted in England found that HbSS and HbSC types accounted for 84% and 16%, respectively, of admissions to the intensive care unit4. The nutritional status of hospitalized adults with SCA remains unclear.

Historically, the SCA patient have impaired nutritional status, coursing with underweight and stunting12,14. In this study were predominantly eutrophic regardless of sex, with malnutrition occurring only in men. Similar results were found in another study of our group, whose the aim was to identify the nutritional status of outpatients SCD adults and found that 60% were normal and 30.8% were overweight/obese20.

Anglin et al21 assessed the nutritional status in eight adults aged 18 to 69 years, and found mean BMI of 25.92 ± 2.84 kg/m2 in women, experiencing higher waist-to-hip ratio and waist circumference, which increases the risk of chronic diseases associated with obesity.

Iwalokum et al22 investigated the nutritional status of 31 patients with stable SCD, 24 with unstable SCD and 22 normal subjects (control). They found that the BMI observed for stable and unstable men was 19.0 ± 0.3 kg/m2 and 18.4 ± 0.2 kg/m2, respectively, and for women was 19.6 ± 0.8 kg/m2 and 17.9 ± 0.3 kg/m2, respectively. Comparing these results with our study, in 2010, we noticed that our patients had better nutritional status, possibly due to better socio-economic conditions in Brazil, when compared to Nigeria.

Thus, the better nutritional status of adults with sickle cell disease observed in this study may be due the effective clinical treatment implemented by the National Comprehensive Care for People with Sickle Cell Disease in Brazil8. Furthermore, there was a process of nutritional transition in many countries, including Brazil. The economic and social changes occurred in Brazil in recent years promoted a sharp decline in malnutrition and increased cases of overweight/obesity in the population as a whole23. The main determinants of this change are sedentary lifestyle and inadequate diets24. A change in food consumption in Brazil was identified in the Household Budget Survey (2008-2009) conducted by the Brazilian Institute of Geography and Statistics (IBGE), which observed inverse association between lower income and higher consumption of high-calorie and hyperglycemic foods, which favors the development of obesity. It is known that people with sickle cell disease are concentrated in lower social classes25, therefore, where the consumption of high-calorie foods prevailed.

In this study, in 2008, there was no significant difference in BMI between genders. In 2010 with the BMI declining among men, significant differences between gender emerged. The women kept the nutritional status during the evaluation period. Iwaokum et al (2011)22 studying the nutritional status of people with SCD (Hb SS) also noted that BMI among women was higher than in men (19.3 ± 0.3 kg/m2 vs. 18.0 ± 0, 2 kg/m2). This can be explained by the smaller amount of lean mass in women, which implies less energy expenditure, as compared to men. In addition, the nutritional status of men may have occurred because of impaired renal function, caused by the well described association between impairment of nutritional status and renal disease. We also observed that women in this study had higher fetal hemoglobin values, which may have mitigated the disease impact on nutritional status. It is known that the presence of higher amounts of fetal hemoglobin decreases intracellular polymerization, with consequent reduction of red blood cells sickling and less morbidity.

Despite the limitations of BMI in identifying body composition, we chose this method for the easy applicability and reproducibility of the collected data, and because it was available in the medical records. In order to identify the body protein status, we used albumin levels and found that, in 2008, two men (4.8%) had hypoalbuminemia. In 2010, only 20 (47.6%) adults recorded albumin in the medical charts, which limited our analysis, and these values were normal. The concern in the maintenance of body protein status stems from its association with several changes that may worsen the sickle cell patient's clinical condition, highlighting the declining ability of protein synthesis related to liver abnormalities, increased frequency of inflammation, increased hepatic production of acute phase proteins, and increased chance of the emergence of leg ulcers.

The care of these patients in the emergency service was constant, with prolonged length of stay in this site. During the emergency stay, no dietary supplement was prescribed, neither those where nutritional risk were identified.

In this study, all patients had painful crises as cause of admission, confirming this to be the leading cause of hospital admission as claimed by other studies13. Platt et al9 reported that the painful crises occur periodically in people with SCD, with greater frequency in people with HbSS (sickle cell anemia). Tawfic et al27 assessed adults with SCD and found that the three leading causes of hospitalization in intensive care units were: acute chest syndrome, painful crises and multiple organ failure. Martins et al8 described febrile or afebrile painful crisis as the most frequent cause of hospitalization and hospital treatment. Hollins et al13 studied the installation of chronic pain in people with SCD and found that pain is more constant among adults, which is in agreement with this study. We have observed high levels of LDH in all subjects, indicating the presence of haemolysis. Some authors show a directly proportional relationship between hemolysis and morbidity. LDH is a marker of disease severity and possible criterion for beginning the use of hydroxyl-urea28.

It is also noteworthy that men and women had biochemical changes worsening renal function and hemolysis, conditions that directly compromise the nutritional status. Renal changes in sickle cell disease begin in childhood, probably because of the presence of hemolysis and intra-parenchymal vaso-occlusive events leading to proteinuria, progressive renal failure and chronic kidney disease4. Chronic kidney disease affects many young adults with SCD29 Decrease in glomerular filtration rate is associated with aging and disease progress30. The pathophysiology of sickle cell nephropathy is not well defined, but may be the result of focal segmental glomerulosclerosis or membran-proliferative glomerulonephritis, hyper-infiltration, albuminuria and iron deposits that contribute to decreased glomerular filtration leading to chronic kidney disease 29,30.

Microalbuminuria and albuminuria are common among the more severe genotypes of SCD and can occur in up to 80% of patients resulting in a glomerulopathy. Approximately 15% of patients will advance to end stage renal disease by their third decade of life. About 25% of patients with hemoglobin SS disease have renal insufficiency defined as a reduced creatinine clearance of < 90 ml/min. Currently, there are no identified treatments that have been shown to be effective in preventing the development of end stage renal disease in patients with sickle cell disease who show evidence of kidney disease early on. However, treatment with an angiotensin-converting enzyme inhibitor may decrease microalbuminuria and proteinuria (Neville and Panepinto, 2011).

Limitations

The lack of anthropometric data in medical records during the various emergency admissions has numerically limited this study. The assessment of the severity of malnutrition by percentage of weight loss was not employed, due to insufficient data available for this analysis. So a single anthropometric index (BMI) was used to assess the nutritional status as a whole, not allowing further discussion of body compartments.

It was evident the need to implement a specific nutrition screening protocol for people with SCD, using objective and subjective parameters, as a positive clinical outcome is influenced by early nutritional intervention, through improved nutritional status, resistance to pain and healing process.

Conclusion

There was a predominance of normal weight in adults with sickle cell disease most frequently admitted to emergency services, which reflects a change in the nutritional profile of these patients. However, men still present high prevalence of malnutrition (11.9%). These results show the need to deploy nutritional screening in emergency services, in order to early detect individuals at nutritional risk.

Referências Bibliográficas

  1. World Health Organization. World Health Assembly Resolution on Sickle Cell Anaemia. WHA59.20. WHO, Geneva, Switzerland [www.who.int/gb].
  2. Alves Al. Mortality study of sickle cell anemia. Inf Epidemiol SUS 1996; 5 (4):45-53.
  3. Bartolucci P; Galactéros F. Clinical management of adult sickle-cell disease. Curr Opin Hematol 2012, 19: 149–155.
  4. Guasch A, Navarrete J, Nass K, and. Zayas CF. Glomerular involvement in adults with sickle cell hemoglobinopathies: prevalence and clinical correlates of progressive renal failure. J Am Soc Nephrol 2006; 17: 2228–2235, doi: 10.1681/ASN.2002010084.
  5. ANVISA. Manual of Diagnosis and Treatment of Sickle Cell Disease, 2001. Disponível em: <http://www.anvisa.gov.br/htm> . Acesso em: 01/05/10.
  6. Al-Lamki, L. Deaths from sickle cell disease in intensive care units. SQU Med J 2012; 12: 133-136.
  7. U.S. Preventive Services Task Force. Screening for hemoglobinopathies. Guidelines from the guide to clinical preventive services. 2nd edition. Baltimore, MD: Williams and Wilkins; 1996.
  8. Martins PRJ, Moraes-Souza H, Silveira TB. Morbidity and mortality in sickle cell disease. Rev. Bras. Hematol. Hemoter 2010; 32 (5): 378 – 383.
  9. Platt OS, Thorington BD, Brambilla DJ, Milner PF, Rosse WF, Vichinsky E, et al. Pain in sickle cell disease: rates and risk factors. N Engl J Med 1991; 325(1): 11
  10. Platt OS, Brambilla DJ, Rosse WF, Milner PF, Castro O, Steinberg MH, et al. Mortality in sickle cell disease: life expectancy and risk factors for early death. N Engl J Med 1994; 330(23):1639-44.
  11. Loureiro MM, Rozenfeld S. Epidemiology of hospitalizations for sickle cell disease in Brazil. Rev. Saúde Pública 2005; 39(6): 943-9.
  12. Miller R G, Segal J, Ashar BH, Leung S, Ahmed S, Siddique S, Rice T, Lanzkron S. High prevalence and correlates of low bone mineral density in young adults with sickle cell disease. American Journal of Hematology 2006; 81: 236–241.
  13. Hollins M, Stonerock GL, Kisaalita NR, Jones S, Orringer E, Gil KM. Detecting the emergence of chronic pain in sickle cell disease. Journal of Pain and Symptom Management 2012, 1-12, doi: 10.1016.
  14. Prasad A. Malnutrition in sickle cell disease patients. Am J Clin Nutr 1997:66:423-4.
  15. Okochi, V I; Okpuzor, J. Micronutrients as therapeutic tools in the management of sickle cell disease, malaria and diabetes. Afr.J.Biotechnol 2005; 4 (13): 1568-1579.
  16. Muskiet FAJ, Muskiet FD, Meiborg G, Schermer JG. Supplementation of patients with homozygous sickle cell disease with zinc, a-tocopherol, vitamin C, soybean oil, and fish oil. Am J Clin Nutr 1991; 54: 736 – 44.
  17. Hankins J. Toward high quality medical care for sickle cell disease: are we there yet? J. Pediatr. (Rio J.) 2010; 86 (4): 256 – 258.
  18. Modell B, Darlison M. Global epidemiology of haemoglobin disorders and derived service indicators. Bull World Health Organ 2008; 86(6): 480-487.
  19. Pells JJ, Presnell KE, Edwards CL, Wood M, Harrison MO, DeCastro L, Johnson S, Feliu M, Canada S, Jonassaint JC, Barker C, Leach-Beale B, Mathis MJ, Applegate K, Holmes A, Byrd G, Robinson E. Moderate chronic pain, weight and dietary intake in African-american adult patients with sickle cell disease. J.Nat Med Assoc 1997 (12): 1622 - 1628.
  20. Lino DL, Freitas ACT, Iglesias RA, Souza KCM, Mataratzis PR, Rocha FHZ, Damião J, Valle JS, Citelli M, Cople-Rodrigues, C dos S (unpublished results). Anthropometric and socio - economic status of adult patients with sickle cell disease as outpatients Nutrition in Hematology HUPE / UERJ. 11th Week Undergraduate UERJ (2011).
  21. Anglin JC, Adkins JS, Johnson AA. Overweight Black adults with homozygous sickle cell disease. J Nat Soco f Allied Health 2011: 21 – 30
  22. Iwalokun BA, Iwalokun SO, Hodonu SO, Aina AO and Agomo PU. Serum levels of leptin in Nigerian patients with sickle cell anaemia. MC Blood Disorders 2011, 11:2 doi:10.1186/1471-2326-11-2.
  23. Batista Filho M; Rissin A. The nutrition transition in Brazil: regional and temporal trends. Book of Public Health, 2003. Rio de Janeiro, 19 (Sup.1): S181-S191.
  24. Kac G. e Velásquez-Meléndez G. The nutrition transition and the epidemiology of obesity in Latin America. Book of Public Health, 2003, 19 (Sup.1): S4-S5.
  25. Naoum, P. Erythrocytes and environmental interferences in sickle cell anemia. Rev. Brazilian Hematologycal and Hemoterapy 2000, v.22, n.1, p. 5-22.
  26. Kamimura MA Avesani CM, Draibe SA, Cuppari L. Resting energy expenditure in patients with chronic kidney disease. Rev. Nutr, 2008; 21(1): 75-84.
  27. Tawfic QA; Kausalya R; Al-Sajee D; Burad J; Mohammed AK; Narayanan A. Adult sickle cell disease. SQU Med J 2012; 12: 177-183.
  28. Kato G J., McGowan V., Machado R F., Little JA., Taylor VI J., Morris CR., Nichols JS., Wang X., Poljakovic M., Morris Jr SM., and Gladwin MT. Lactate dehydrogenase as a biomarker of hemolysis-associated nitric oxide resistance, priapism, leg ulceration, pulmonary hypertension, and death in patients with sickle cell disease. Blood. 2006; 107 (6): 2279- 2285.
  29. Aygun B, Mortier NA, Smeltzer MP, Hankins JS, Ware R E. Glomerular hyperfiltration and albuminuria in children with sickle cell anemia. Pediatr Nephrol (2011) 26:1285–1290. DOI 10.1007/s00467-011-1857-2.
  30. Silva Junior GB, Libório AB, Vieira APF, Couto Bem AX, Lopes Filho AS, Figueiredo Filho AC, Guedes ALMO, Souza JH, Costa CMBE, Costa R, Daher EF. Evaluation of renal function in sickle cell disease patients in Brazil. Braz. J. Med. Biol Res. 2012 45 (7): 652-655.
  31. Neville KA and Panepinto JA. Pharmacotherapy of Sickle Cell Disease. 18th Expert Committee on the Selection and Use of Essential Medicines, 2011. In http://www.who.int/selection_medicines/committees/expert/18/applications/Sicklecell.pdf
  32. Bender MA; Hobbs W. Sickle cell disease. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014. 2003 Sep 15 [updated 2012 May 17].

Notas

Conflict of Interest

We declare that we have no conflicts of interest in the authorship or publication of this contribution.

Autor correspondente

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