ABSTRACT

Objective:

To compare reference intervals (RI) of blood counts of Brazilian adults with and without sickle cell trait (SCT).

Methods:

Cross-sectional study, based on the National Health Survey, 2014-2015, composed of 8,952 individuals. The sample of patients with SCT was composed of 234 adults. The RIs of adults with and without SCT were compared in the study “Reference values for laboratory tests of blood count in the Brazilian adult population: National Health Survey”, by Rosenfeld et al. (2019). The parametric method and the Student's t test were used for comparison (p≤0.05).

Results:

There were statistically significant differences between RIs of adults with and without SCT as far as sex is concerned for hemoglobin, MCV, MCH, MCHC, white blood cells, absolute lymphocytes, mean platelet volume and RDW; At all ages, for white blood cells and RDW in men and for MCV, MCH, MCHC, mean platelet volume and RDW in women; Between 18 to 59 years, for MCH, MCV, MCHC, neutrophils, lymphocytes and platelets in men and in women for lymphocytes, red blood cells, white blood cells, neutrophils, eosinophils, monocytes and platelets; From 60 years old on, for hemoglobin and hematocrit in men and in women for hematocrit, white blood cells, neutrophils and platelets; In white, black and brown people for white blood cells, neutrophils and platelets (p<0.05).

Conclusion:

Brazilian adults with SCT had lower counts of hemoglobin, MCV, MCH, MCHC, white blood cells and higher RDW than without SCT. The results show the importance of genetic counseling and further research to support the proper management of this condition in Brazil.

Keywords:
Health surveys; Reference values; Blood cell count; Sickle cell trait; Brazil

INTRODUCTION

Sickle cell trait (SCT) is a condition described as usually asymptomatic¹1 Ashorobi D, Ramsey A, Yarrarapu SNS, Bhatt R. Sickle cell trait. StatPearls [Internet]. Treasure Island: StatPearls Publishing; 2022.,²2 Lervolino LG, Baldin PEA, Picado SM, Calil KB, Viel AA, Campos LAF. Prevalence of sickle cell disease and sickle cell trait in national neonatal screening studies. Rev Bras Hematol Hemoter 2011; 33(1): 49-54. https://doi.org/10.5581/1516-8484.20110015
https://doi.org/10.5581/1516-8484.201100... . Its etiology stems from the presence of sickle cell hemoglobin (HbS), the result of a mutation after the replacement of A by T in codon 6 of the hemoglobin beta chain. As a consequence, glutamic acid changes into the amino acid valine. Valine-type hemoglobin leads to the sickling of red blood cells when exposed to low oxygen threshold¹1 Ashorobi D, Ramsey A, Yarrarapu SNS, Bhatt R. Sickle cell trait. StatPearls [Internet]. Treasure Island: StatPearls Publishing; 2022.. Affected individuals inherit the hemoglobin A (HbA) and HbS genes from their parents. Thus, they are heterozygous with an abnormal allele of the hemoglobin beta gene¹1 Ashorobi D, Ramsey A, Yarrarapu SNS, Bhatt R. Sickle cell trait. StatPearls [Internet]. Treasure Island: StatPearls Publishing; 2022..

The importance of screening³3 El Ariss AB, Younes M, Matar J, Berjaoui Z. Prevalence of sickle cell trait in the southern suburb of Beirut, Lebanon. Mediterr J Hematol Infect Dis 2016; 8(1): e2016015. https://doi.org/10.4084/MJHID.2016.015
https://doi.org/10.4084/MJHID.2016.015... and genetic counseling in people with SCT is highlighted as a means to clarify people about the risk of having children with sickle cell disease (SCD), since it is inherited through an autosomal recessive gene from both parents²2 Lervolino LG, Baldin PEA, Picado SM, Calil KB, Viel AA, Campos LAF. Prevalence of sickle cell disease and sickle cell trait in national neonatal screening studies. Rev Bras Hematol Hemoter 2011; 33(1): 49-54. https://doi.org/10.5581/1516-8484.20110015
https://doi.org/10.5581/1516-8484.201100... . In SCD, individuals have two copies of the beta globin variant and the primary hemoglobin present in their red blood cells (HbS), making them homozygous (HbSS)⁴4 John N. A review of clinical profile in sickle cell traits. Oman Med J 2010; 25(1): 3-8. https://doi.org/10.5001/omj.2010.2
https://doi.org/10.5001/omj.2010.2... . The morbidity and mortality and severity of SCD is associated with microvasculature occlusions with tissue ischemia, leading to pain crises; organic lesions with functional asplenia; cerebral vasculopathy; kidney, lung and heart failure⁴4 John N. A review of clinical profile in sickle cell traits. Oman Med J 2010; 25(1): 3-8. https://doi.org/10.5001/omj.2010.2
https://doi.org/10.5001/omj.2010.2... ,⁵5 Diniz D, Guedes C, Barbosa L, Tauil PL, Magalhães I. Prevalence of sickle cell trait and sickle cell anemia among newborns in the Federal District, Brazil, 2004 to 2006. Cad Saude Publica 2009; 25(1): 188-94. https://doi.org/10.1590/s0102-311x2009000100020
https://doi.org/10.1590/s0102-311x200900... .

Although SCT is commonly asymptomatic, there is evidence of cases of sudden death²2 Lervolino LG, Baldin PEA, Picado SM, Calil KB, Viel AA, Campos LAF. Prevalence of sickle cell disease and sickle cell trait in national neonatal screening studies. Rev Bras Hematol Hemoter 2011; 33(1): 49-54. https://doi.org/10.5581/1516-8484.20110015
https://doi.org/10.5581/1516-8484.201100... in affected people. Such cases happen because of complications from hypoxia, including sudden death⁶6 Tsaras G, Owusu-Ansah A, Boateng FO, Amoateng-Adjepong Y. Complications associated with sickle cell trait: a brief narrative review. Am J Med 2009; 122(6): 507-12. https://doi.org/10.1016/j.amjmed.2008.12.020
https://doi.org/10.1016/j.amjmed.2008.12... , hematuria, hyposthenuria, pulmonary embolism, splenic infarction²2 Lervolino LG, Baldin PEA, Picado SM, Calil KB, Viel AA, Campos LAF. Prevalence of sickle cell disease and sickle cell trait in national neonatal screening studies. Rev Bras Hematol Hemoter 2011; 33(1): 49-54. https://doi.org/10.5581/1516-8484.20110015
https://doi.org/10.5581/1516-8484.201100... ,⁶6 Tsaras G, Owusu-Ansah A, Boateng FO, Amoateng-Adjepong Y. Complications associated with sickle cell trait: a brief narrative review. Am J Med 2009; 122(6): 507-12. https://doi.org/10.1016/j.amjmed.2008.12.020
https://doi.org/10.1016/j.amjmed.2008.12... , urinary tract infection in women, end-stage kidney disease, polycystic kidney disease, heart attack, stroke, eye problems, and lower limb ulcers⁴4 John N. A review of clinical profile in sickle cell traits. Oman Med J 2010; 25(1): 3-8. https://doi.org/10.5001/omj.2010.2
https://doi.org/10.5001/omj.2010.2... .

SCT is widely distributed continental-wise⁷7 Murao M, Ferraz MHC. Traço falciforme: heterozigose para hemoglobina S. Rev Bras Hematol Hemoter 2007; 29(3): 223-5. https://doi.org/10.1590/S1516-84842007000300006
https://doi.org/10.1590/S1516-8484200700... , being more frequent in people of African descent¹1 Ashorobi D, Ramsey A, Yarrarapu SNS, Bhatt R. Sickle cell trait. StatPearls [Internet]. Treasure Island: StatPearls Publishing; 2022.,²2 Lervolino LG, Baldin PEA, Picado SM, Calil KB, Viel AA, Campos LAF. Prevalence of sickle cell disease and sickle cell trait in national neonatal screening studies. Rev Bras Hematol Hemoter 2011; 33(1): 49-54. https://doi.org/10.5581/1516-8484.20110015
https://doi.org/10.5581/1516-8484.201100... ,⁸8 Antwi-Boasiako C, Ekem I, Abdul-Rahman M, Sey F, Doku A, Dzudzor B, et al. Hematological parameters in Ghanaian sickle cell disease patients. J Blood Med 2018; 9: 203-9. https://doi.org/10.2147/JBM.S169872
https://doi.org/10.2147/JBM.S169872... . It is estimated that there are 300 million people with SCT around the world¹1 Ashorobi D, Ramsey A, Yarrarapu SNS, Bhatt R. Sickle cell trait. StatPearls [Internet]. Treasure Island: StatPearls Publishing; 2022.,³3 El Ariss AB, Younes M, Matar J, Berjaoui Z. Prevalence of sickle cell trait in the southern suburb of Beirut, Lebanon. Mediterr J Hematol Infect Dis 2016; 8(1): e2016015. https://doi.org/10.4084/MJHID.2016.015
https://doi.org/10.4084/MJHID.2016.015... , with the highest prevalence in Equatorial Africa, Arabia, India, Israel, Turkey, Greece and Italy, reaching a 50% prevalence in certain regions of these countries⁷7 Murao M, Ferraz MHC. Traço falciforme: heterozigose para hemoglobina S. Rev Bras Hematol Hemoter 2007; 29(3): 223-5. https://doi.org/10.1590/S1516-84842007000300006
https://doi.org/10.1590/S1516-8484200700... . In Brazil, the prevalence varies between 2 and 8%⁷7 Murao M, Ferraz MHC. Traço falciforme: heterozigose para hemoglobina S. Rev Bras Hematol Hemoter 2007; 29(3): 223-5. https://doi.org/10.1590/S1516-84842007000300006
https://doi.org/10.1590/S1516-8484200700... . Studies with data from the National Health Survey (PNS – Pesquisa Nacional de Saúde), between 2014 and 2015, identified a prevalence of 2.49% in adults⁹9 Rosenfeld LG, Bacal NS, Cuder MAM, Silva AG, Machado ÍE, Pereira CA, et al. Prevalence of hemoglobinopathies in the Brazilian adult population: National Health Survey 2014-2015. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190007.SUPL.2. https://doi.org/10.1590/1980-549720190007.supl.2
https://doi.org/10.1590/1980-54972019000... .

SCD, on the other hand, is among the genetic pathologies of greatest epidemiological importance in Brazil and in other nations²2 Lervolino LG, Baldin PEA, Picado SM, Calil KB, Viel AA, Campos LAF. Prevalence of sickle cell disease and sickle cell trait in national neonatal screening studies. Rev Bras Hematol Hemoter 2011; 33(1): 49-54. https://doi.org/10.5581/1516-8484.20110015
https://doi.org/10.5581/1516-8484.201100... , considered as a public health problem by the World Health Organization (WHO)³3 El Ariss AB, Younes M, Matar J, Berjaoui Z. Prevalence of sickle cell trait in the southern suburb of Beirut, Lebanon. Mediterr J Hematol Infect Dis 2016; 8(1): e2016015. https://doi.org/10.4084/MJHID.2016.015
https://doi.org/10.4084/MJHID.2016.015... . Worldwide, in 2010, SCD affected 305,800 newborns, and an increase is expected to 404,200 by 2050¹⁰10 Piel FB, Hay SI, Gupta S, Weatherall DJ, Williams TN. Global burden of sickle cell anaemia in children under five, 2010-2050: modelling based on demographics, excess mortality, and interventions. PLoS Med 2013; 10(7): e1001484. https://doi.org/10.1371/journal.pmed.1001484
https://doi.org/10.1371/journal.pmed.100... . In Brazil, the prevalence ranges from 1.1 to 9.8% and from 0.8 to 60 per 100,000 live births in different regions of the country²2 Lervolino LG, Baldin PEA, Picado SM, Calil KB, Viel AA, Campos LAF. Prevalence of sickle cell disease and sickle cell trait in national neonatal screening studies. Rev Bras Hematol Hemoter 2011; 33(1): 49-54. https://doi.org/10.5581/1516-8484.20110015
https://doi.org/10.5581/1516-8484.201100... .

Changes in hematological parameters have been identified in people with SCD⁸8 Antwi-Boasiako C, Ekem I, Abdul-Rahman M, Sey F, Doku A, Dzudzor B, et al. Hematological parameters in Ghanaian sickle cell disease patients. J Blood Med 2018; 9: 203-9. https://doi.org/10.2147/JBM.S169872
https://doi.org/10.2147/JBM.S169872... ,¹¹11 Lu M, Rab MA, Shevkoplyas SS, Sheehan VA. Blood rheology biomarkers in sickle cell disease. Exp Biol Med (Maywood) 2020; 245(2): 155-65. https://doi.org/10.1177/1535370219900494
https://doi.org/10.1177/1535370219900494... . In people with SCT, although hematological parameters are usually described as normal or without important laboratory alterations⁴4 John N. A review of clinical profile in sickle cell traits. Oman Med J 2010; 25(1): 3-8. https://doi.org/10.5001/omj.2010.2
https://doi.org/10.5001/omj.2010.2... , this condition can lead to vaso-occlusion due to rigid erythrocytes in the face of pathological processes that cause hypoxia, acidosis, dehydration, hyperosmolality or hypothermia¹¹11 Lu M, Rab MA, Shevkoplyas SS, Sheehan VA. Blood rheology biomarkers in sickle cell disease. Exp Biol Med (Maywood) 2020; 245(2): 155-65. https://doi.org/10.1177/1535370219900494
https://doi.org/10.1177/1535370219900494... .

Differences in the hematological parameters of people with SCT were found in populations from other countries, which means that the reference intervals (RI) of blood counts may suffer geographic and ethnic influences³3 El Ariss AB, Younes M, Matar J, Berjaoui Z. Prevalence of sickle cell trait in the southern suburb of Beirut, Lebanon. Mediterr J Hematol Infect Dis 2016; 8(1): e2016015. https://doi.org/10.4084/MJHID.2016.015
https://doi.org/10.4084/MJHID.2016.015... ,⁸8 Antwi-Boasiako C, Ekem I, Abdul-Rahman M, Sey F, Doku A, Dzudzor B, et al. Hematological parameters in Ghanaian sickle cell disease patients. J Blood Med 2018; 9: 203-9. https://doi.org/10.2147/JBM.S169872
https://doi.org/10.2147/JBM.S169872... . However, studies on the hematological profile of patients with SCT in Brazil are scarce. This study steps forward by providing, in an unprecedented way, through PNS exams, the hematological parameters of adults with SCT and the differences found in parameters of adults without SCT in the country. Our findings may contribute to support the handling of SCT in Brazil.

Thus, this study aimed to compare the RI of blood counts of Brazilian adults with and without SCT.

METHODS

Study Design

Cross-sectional study with data from laboratory tests of the PNS carried between 2014 and 2015.

Context and data source

The PNS is a national household-based survey carried out by the Brazilian Institute of Geography and Statistics (IBGE – Instituto Brasileiro de Geografia e Estatística), in partnership with the Ministry of Health¹²12 Szwarcwald CL, Malta DC, Souza Júnior PRB, Almeida WS, Damacena GN, Pereira CA, et al. Laboratory exams of the National Health Survey: methodology of sampling, data collection and analysis. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190004.SUPL.2. https://doi.org/10.1590/1980-549720190004.supl.2
https://doi.org/10.1590/1980-54972019000... .

The PNS 2013 used probabilistic sampling by clusters in three stages, with stratification of the primary sampling units (UPA), being selected in the first, second and third stages, respectively: census tracts; 10 to 14 households in each UPA; and one resident over the age of 18. At all stages, the selection processes were carried out by simple random sampling (SRS). Records of 64,348 households were obtained, of which 60,202 were interviews with adults. Furthermore, the collection of exams was planned in a subsample of 25% of the census sectors, being collected, between 2014 and 2015, from 8,952 adults¹²12 Szwarcwald CL, Malta DC, Souza Júnior PRB, Almeida WS, Damacena GN, Pereira CA, et al. Laboratory exams of the National Health Survey: methodology of sampling, data collection and analysis. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190004.SUPL.2. https://doi.org/10.1590/1980-549720190004.supl.2
https://doi.org/10.1590/1980-54972019000... .

Due to the complex sampling design of the PNS and the unequal selection probabilities, sample weights were used¹²12 Szwarcwald CL, Malta DC, Souza Júnior PRB, Almeida WS, Damacena GN, Pereira CA, et al. Laboratory exams of the National Health Survey: methodology of sampling, data collection and analysis. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190004.SUPL.2. https://doi.org/10.1590/1980-549720190004.supl.2
https://doi.org/10.1590/1980-54972019000... . In order to used the PNS laboratory database, weights were calculated by post-stratification procedures by sex, age range, race/skin color and level of education according to major region, from the total sample of the research¹²12 Szwarcwald CL, Malta DC, Souza Júnior PRB, Almeida WS, Damacena GN, Pereira CA, et al. Laboratory exams of the National Health Survey: methodology of sampling, data collection and analysis. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190004.SUPL.2. https://doi.org/10.1590/1980-549720190004.supl.2
https://doi.org/10.1590/1980-54972019000... .

Laboratory samples were collected at any time of the day and without fasting. For blood count collection and hemoglobin electrophoresis, tubes with ethylenediaminetetraacetic acid (EDTA) were used. The samples were analyzed using an automatic cell analyzer¹²12 Szwarcwald CL, Malta DC, Souza Júnior PRB, Almeida WS, Damacena GN, Pereira CA, et al. Laboratory exams of the National Health Survey: methodology of sampling, data collection and analysis. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190004.SUPL.2. https://doi.org/10.1590/1980-549720190004.supl.2
https://doi.org/10.1590/1980-54972019000... . Hemoglobinopathies were searched by the HPLC method, and the results of individual tests were interpreted, providing normal, homozygous or heterozygous parameters for Hemoglobin S (HbS), Hemoglobin C (HbC), Hemoglobin D (HbD) and other hemoglobinopathies⁹9 Rosenfeld LG, Bacal NS, Cuder MAM, Silva AG, Machado ÍE, Pereira CA, et al. Prevalence of hemoglobinopathies in the Brazilian adult population: National Health Survey 2014-2015. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190007.SUPL.2. https://doi.org/10.1590/1980-549720190007.supl.2
https://doi.org/10.1590/1980-54972019000... . More methodological details are available in other publications¹²12 Szwarcwald CL, Malta DC, Souza Júnior PRB, Almeida WS, Damacena GN, Pereira CA, et al. Laboratory exams of the National Health Survey: methodology of sampling, data collection and analysis. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190004.SUPL.2. https://doi.org/10.1590/1980-549720190004.supl.2
https://doi.org/10.1590/1980-54972019000... ,¹³13 Instituto Brasileiro de Geografia e Estatística. Pesquisa Nacional de Saúde 2013: percepção do estado de saúde, estilos de vida e doenças crônicas: Brasil, Grandes Regiões e Unidades da Federação. Rio de Janeiro: IBGE; 2014..

The PNS database and questionnaires used in this study are available at: www.pns.fiocruz.br.

Participants

Participants were adults aged 18 and over. The PNS database, composed of 8,952 individuals, was used. A total of 330 adults were excluded due to absence of test results, insufficient material, sample loss and hemolysis⁹9 Rosenfeld LG, Bacal NS, Cuder MAM, Silva AG, Machado ÍE, Pereira CA, et al. Prevalence of hemoglobinopathies in the Brazilian adult population: National Health Survey 2014-2015. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190007.SUPL.2. https://doi.org/10.1590/1980-549720190007.supl.2
https://doi.org/10.1590/1980-54972019000... . In this study, data from 234 adults with SCT were analyzed. Data analyzed from adults without SCT were extracted from the study by Rosenfeld et al.¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... .

Reference Intervals

Intervals of adults with sickle cell trait:

The RI of blood count parameters (described below) of adults with SCT were estimated considering the lower limit (LL) as the mean −1.96 SD (standard deviation) and the upper limit (UL), the mean +1.96 SD (standard deviation).

Intervals of adults without sickle cell trait

For adults without SCT, the means and RI (LL and UL) of blood count parameters from the study by Rosenfeld et al.¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... were used.

Variables

The variables were: sociodemographic: sex (male; female); age (age range in years: 18 to 59; 60 or older); race/skin color (white; brown; black). Presence of SCT: (yes; no). Blood count parameters: red series: red blood cells (millions/mm³3 El Ariss AB, Younes M, Matar J, Berjaoui Z. Prevalence of sickle cell trait in the southern suburb of Beirut, Lebanon. Mediterr J Hematol Infect Dis 2016; 8(1): e2016015. https://doi.org/10.4084/MJHID.2016.015
https://doi.org/10.4084/MJHID.2016.015... ); hemoglobin (g/dL); hematocrit (%); mean corpuscular volume (MCV) (fL); mean corpuscular hemoglobin (MCH) (pg); mean corpuscular hemoglobin concentration (MCHC) (g/dL); erythrocyte distribution range (RDW) (%). White series: white blood cells (mm³3 El Ariss AB, Younes M, Matar J, Berjaoui Z. Prevalence of sickle cell trait in the southern suburb of Beirut, Lebanon. Mediterr J Hematol Infect Dis 2016; 8(1): e2016015. https://doi.org/10.4084/MJHID.2016.015
https://doi.org/10.4084/MJHID.2016.015... ); absolute neutrophils (mm³3 El Ariss AB, Younes M, Matar J, Berjaoui Z. Prevalence of sickle cell trait in the southern suburb of Beirut, Lebanon. Mediterr J Hematol Infect Dis 2016; 8(1): e2016015. https://doi.org/10.4084/MJHID.2016.015
https://doi.org/10.4084/MJHID.2016.015... ); absolute eosinophils (mm³3 El Ariss AB, Younes M, Matar J, Berjaoui Z. Prevalence of sickle cell trait in the southern suburb of Beirut, Lebanon. Mediterr J Hematol Infect Dis 2016; 8(1): e2016015. https://doi.org/10.4084/MJHID.2016.015
https://doi.org/10.4084/MJHID.2016.015... ); absolute basophils (mm³3 El Ariss AB, Younes M, Matar J, Berjaoui Z. Prevalence of sickle cell trait in the southern suburb of Beirut, Lebanon. Mediterr J Hematol Infect Dis 2016; 8(1): e2016015. https://doi.org/10.4084/MJHID.2016.015
https://doi.org/10.4084/MJHID.2016.015... ); absolute lymphocytes (mm³); absolute monocytes (mm³); platelets (μl); mean platelet volume (fL).

Statistical analyses

The RIs were estimated by the parametric method. The sample was partitioned according to sex, age and race/skin color. For each partition, the means, SD and RI linked to the LL and UL were calculated (mean ± 1.96 SD) according to sex, age group and race/skin color. As the PNS sample was large enough and close to normal distribution, the Student's t test was used to compare RIs of adults with and without SCT in the study by Rosenfeld et al.¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... . The significance level adopted was 5%.

Data analyses were performed using the Data Analysis and Statistical Software (Stata), version 14, with the set of commands in the survey module, which considers post-stratification weights.

Ethical Aspects

The PNS was approved by the National Research Ethics Committee of the National Health Council (Opinion No. 328,159). Adult's participation was voluntary, and confidentiality of information was guaranteed¹³13 Instituto Brasileiro de Geografia e Estatística. Pesquisa Nacional de Saúde 2013: percepção do estado de saúde, estilos de vida e doenças crônicas: Brasil, Grandes Regiões e Unidades da Federação. Rio de Janeiro: IBGE; 2014..

RESULTS

For the red series, there were statistically significant differences for some blood count parameters when comparing RIs of adults with and without SCT¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... (p≤0.05) (Table 1). Men and women with SCT had lower mean values of hemoglobin, VCM, MCH, MCHC (Table 1) when compared to those without SCT¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... , as one can see from the means and RIs of the study by Rosenfeld et al.¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... displayed in Table S1. For RDW, the means of men and women with SCT were higher than those without SCT¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... . Men with SCT still had lower hematocrit means than those without SCT ¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... (Tables 1 and S1).

Regarding the white series, for both sexes, statistically significant differences were observed in the RIs of some parameters of the blood count of men and women with SCT compared to those without SCT¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... (p≤0.05) (Table 2). The means of white blood cells, neutrophils, lymphocytes and platelet volume were lower in men and women with SCT than in those without SCT¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... . Women with SCT also had higher mean eosinophils and platelets values than those without SCT¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... , and men with SCT had lower mean platelets than those without SCT¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... (Tables 2 and S1).

With regard to age, for the red series, there were statistically significant differences in the RIs of men with SCT compared to those without SCT¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... (p≤0.05) (Table S2). Means were lower between 18- and 59-year-olds for MCH, MCV and MCHC, and from 60 years onwards for hemoglobin, hematocrit and MCH in men with SCT than in those without SCT¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... . RDW means were higher in men aged between 18 and 59 years old with SCT than in those without SCT¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... . The means of hemoglobin, MCV, MCH and MCHC in women aged between 18 and 59 years and 60 years or older were lower in those with SCT than in those without SCT¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... . Women with SCT aged 60 years or older had lower hematocrit means compared to those without SCT¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... . Higher mean red blood cells and RDW were found in women aged 18 to 59 years with SCT compared to those without SCT¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... (Tables S2 and S3).

For the white series, there were statistically significant differences in the RIs of adults with and without SCT¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... when stratified by age (p≤0.05) (Table S4). Mean white blood cell values were lower in men with SCT than in those without SCT¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... aged between 18 and 59 years and 60 and older. Lower means of neutrophils, lymphocytes, platelets and platelet volume were identified in men with SCT when compared to those without SCT¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... in the two age groups. For women with SCT, the mean platelet volumes were lower in both age groups than for those without SCT¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... and aged 60 and older, women with SCT had lower mean white blood cells, neutrophils and platelets compared to those without SCT¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... . Also in women with SCT compared to those without SCT¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... , higher means of white blood cells, neutrophils, eosinophils, monocytes and platelets were found in the age group 18-59 years (p≤0.05) (Table S3 and S4).

There were differences when comparing the RIs of some blood count parameters between men and women with and without SCT¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... of white, brown and black skin for hemoglobin, white blood cells, neutrophils and platelets (p≤0.05) (Table S5). The means were slightly lower for both sexes for hemoglobin in brown adults with SCT than in those without SCT¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... . In white, black and brown men with SCT, the mean white blood cells, neutrophils and platelets were lower than in those without SCT¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... . White women with SCT had lower means of white blood cells and neutrophils than those without SCT¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... , and black women had lower platelet means. In black and brown women with SCT, higher mean values of white blood cells and neutrophils were found, while for white and brown women, mean values of platelets were higher compared to those without SCT¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... (Tables S5 and S6).

DISCUSSION

This study assessed for the first time, using laboratory PNS data, the differences in hematological RI of Brazilian adults with and without SCT¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... . The findings show lower counts for hemoglobin, MCV, MCH, MCHC, white blood cells, lymphocytes and mean platelet volume, and higher counts for RDW in adults with SCT compared to those without SCT¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... , for both sexes. When stratifying according to sex and age, differences were identified in some parameters of white and red series when comparing adults with and without SCT¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... . Furthermore, differences were found in the RI of white, black and brown adults with SCT for white blood cells, neutrophils and platelets, and also in the brown adults for hemoglobin, when compared to those without SCT¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... . Such findings show the relevance of knowing the hematological profile of people with SCT for an adequate management of this condition in the country.

Bearing in mind that hematological parameters of people with SCT usually do not show important laboratory alterations⁴4 John N. A review of clinical profile in sickle cell traits. Oman Med J 2010; 25(1): 3-8. https://doi.org/10.5001/omj.2010.2
https://doi.org/10.5001/omj.2010.2... , the differences found in the RI of some parameters of the blood count of Brazilian adults with and without SCT¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... point to the need for further studies to better understand the clinical implications in people with this condition.

In this study, the results found for the blood count RIs in adults with and without SCT¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... , according to sex, were consistent with a study carried out in Ghana, in which individuals with and without SCD⁸8 Antwi-Boasiako C, Ekem I, Abdul-Rahman M, Sey F, Doku A, Dzudzor B, et al. Hematological parameters in Ghanaian sickle cell disease patients. J Blood Med 2018; 9: 203-9. https://doi.org/10.2147/JBM.S169872
https://doi.org/10.2147/JBM.S169872... were compared. With regard to the red blood count series, in Brazilian adults of both sexes with SCT, the altered values of hemoglobin, MCHC and MCV indicate anemia¹⁵15 Chaparro CM, Suchdev PS. Anemia epidemiology, pathophysiology, and etiology in low- and middle-income countries. Ann N Y Acad Sci 2019; 1450(l): 15-31. https://doi.org/10.1111/nyas.14092
https://doi.org/10.1111/nyas.14092... –¹⁸18 World Health Organization. Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. Vitamin and mineral nutrition information system [Internet]. Genebra: World Health Organization; 2011 [cited on Aug 20, 2018]. Available at: https://apps.who.int/iris/bitstream/handle/10665/85839/WHO_NMH_NHD_MNM_11.1_eng.pdf
https://apps.who.int/iris/bitstream/hand... , microcytosis¹⁷17 Williamson AM, Snyder LM. Wallach: interpretação de exames laboratoriais. 10ᵃ ed. Rio de Janeiro: Guanabara Koogam; 2016.–¹⁹19 Bain BJ. Células sanguíneas: um guia prático. 5ᵃ ed. Porto Alegre: Artmed; 2016. and hypochromia¹⁶16 Machado ÍE, Malta DC, Bacal NS, Rosenfeld LGM. Prevalence of anemia in Brazilian adults and elderly. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190008.SUPL.2. https://doi.org/10.1590/1980-549720190008.supl.2
https://doi.org/10.1590/1980-54972019000... ,¹⁷17 Williamson AM, Snyder LM. Wallach: interpretação de exames laboratoriais. 10ᵃ ed. Rio de Janeiro: Guanabara Koogam; 2016., unlike adults without SCT, whose reference values were unchanged¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... . Furthermore, low MCHC values in adults with SCT may be associated with iron deficiency anemia²⁰20 Koduri PR. Iron in sickle cell disease: a review why less is better. Am J Hematol. 2003;73(1):59-63. https://doi.org/10.1002/ajh.10313
https://doi.org/10.1002/ajh.10313... or thalassemias²¹21 Rachmilewitz EA. The role of intracellular hemoglobin precipitation, low MCHC, and iron overload on red blood cell membrane peroxidation in thalassemia. Birth Defects Orig Artic Ser 1976; 12(8): 123-33.. Other findings in these people with SCT refer to hypochromic microcytic anemia with high RDW, which is also characteristic of lack of iron from nutritional deficit, deficiency in absorption due to gastrointestinal alterations and chronic loss of this micronutrient²²22 Zakai NA, McClure LA, Prineas R, Howard G, McClellan W, Holmes CE, et al. Correlates of anemia in American blacks and whites: the REGARDS Renal Ancillary Study. Am J Epidemiol 2009; 169(3): 355-64. https://doi.org/10.1093/aje/kwn355
https://doi.org/10.1093/aje/kwn355... , as evidenced by the UL of RDW.

This finding is alarming due to the possibility of malnutrition in people with SCT in Brazil, especially when taking into account that chronic hemolysis results in greater availability of iron, and its deficiency is unlikely in SCD²³23 Moreira AS, Silva RAA. Anemia ferropriva em portadores de anemia falciforme: a importância de se avaliar o estado nutricional de ferro. Rev Ciênc Méd Biol 2014; 13(2): 236-41.,²⁴24 Akinbami A, Dosunmu A, Adediran A, Oshinaike O, Adebola P, Arogundade O. Haematological values in homozygous sickle cell disease in steady state and haemoglobin phenotypes AA controls in Lagos, Nigeria. BMC Res Notes 2012; 5: 396. https://doi.org/10.1186/1756-0500-5-396
https://doi.org/10.1186/1756-0500-5-396... . This highlights the need to intensify actions in the field of food security in Brazil, with special attention to the most vulnerable groups¹⁶16 Machado ÍE, Malta DC, Bacal NS, Rosenfeld LGM. Prevalence of anemia in Brazilian adults and elderly. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190008.SUPL.2. https://doi.org/10.1590/1980-549720190008.supl.2
https://doi.org/10.1590/1980-54972019000... . This situation was aggravated by the COVID-19 pandemic, which put Brazil back on the hunger map²⁵25 Alpino TMA, Santos CRB, Barros DC, Freitas CM. COVID-19 and food and nutritional (in)security: action by the Brazilian Federal Government during the pandemic, with budget cuts and institutional dismantlement. Cad Saude Publica 2020; 36(8): e00161320. https://doi.org/10.1590/0102-311X00161320
https://doi.org/10.1590/0102-311X0016132... , and may have contributed to the worsening of this scenario in people with SCT and SCD. In compliance with the national and international pacts made by Brazil to reduce iron deficiency anemia by 2030, this should be one of the priorities in public health¹⁶16 Machado ÍE, Malta DC, Bacal NS, Rosenfeld LGM. Prevalence of anemia in Brazilian adults and elderly. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190008.SUPL.2. https://doi.org/10.1590/1980-549720190008.supl.2
https://doi.org/10.1590/1980-54972019000... .

Blood count analyses by age followed similar patterns of analyses by sex, occurring in men and women with SCT of all ages, when compared to those without SCT¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... , alterations in the RI of MCV, MCH and MCHC. Possible explanations are the conditions of access health and food, as well as health assistance, once the clinical variability of SCD is influenced by social and economic factors²⁶26 Guimarães CTL, Coelho GO. The importance of genetic counseling at sickle cell anemia. Cien Saude Colet 2010; 15 Suppl 1: 1733-40. https://doi.org/10.1590/s1413-81232010000700085
https://doi.org/10.1590/s1413-8123201000... —which may also be happening for SCT. Other possible explanations for the lower values of MCV, MCH and MCHC observed in adults with SCT are the effects of anemia of chronic disease, higher risk of infections and the degree of hemolysis in which such parameters are reduced²⁴24 Akinbami A, Dosunmu A, Adediran A, Oshinaike O, Adebola P, Arogundade O. Haematological values in homozygous sickle cell disease in steady state and haemoglobin phenotypes AA controls in Lagos, Nigeria. BMC Res Notes 2012; 5: 396. https://doi.org/10.1186/1756-0500-5-396
https://doi.org/10.1186/1756-0500-5-396... .

When analyzing the white blood count series according to sex, with regard to white blood cells and neutrophils, what draws attention are the even lower mean values found in Brazilian adults with SCT compared to those without SCT. In the analyses by age, the presence of leukopenia²⁷27 Karazawa EH, Jamra M. Parâmetros hematológicos normais. Rev Saúde Pública 1989; 23(1): 58-66. https://doi.org/10.1590/s0034-89101989000100008
https://doi.org/10.1590/s0034-8910198900... is noted by the LL in all age groups and in both sexes, and the presence of leukocytosis²⁷27 Karazawa EH, Jamra M. Parâmetros hematológicos normais. Rev Saúde Pública 1989; 23(1): 58-66. https://doi.org/10.1590/s0034-89101989000100008
https://doi.org/10.1590/s0034-8910198900... in women aged between 18 and 59 years identified by the UL. The literature describes that the decline in leukocytes is related to aging as a result of immune response to the extent that exposure to pathogens occurs²⁸28 Adeli K, Raizman JE, Chen Y, Higgins V, Nieuwesteeg M, Abdelhaleem M, et al. Complex biological profile of hematologic markers across pediatric, adult, and geriatric ages: establishment of robust pediatric and adult reference intervals on the basis of the Canadian Health Measures Survey. Clin Chem 2015; 61(8): 1075-86. https://doi.org/10.1373/clinchem.2015.240531
https://doi.org/10.1373/clinchem.2015.24... ,²⁹29 Nah EH, Kim S, Cho S, Cho HI. Complete blood count reference intervals and patterns of changes aucross pediatric, adult, and geriatric ages in Korea. Ann Lab Med 2018; 38(6): 503-11. https://doi.org/10.3343/alm.2018.38.6.503
https://doi.org/10.3343/alm.2018.38.6.50... . Leukopenia can also result from viral and bacterial infections and medication use, and it is interchangeable with neutropenia³⁰30 Ing VW. The etiology and management of leukopenia. Can Fam Physician 1984; 30: 1835-9., as one can see by the LL of neutrophil found in Brazilian men and even women with SCT, whose mean values were slightly higher than in those without SCT¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... . Managing these situations requires identification of cause and effective therapy³⁰30 Ing VW. The etiology and management of leukopenia. Can Fam Physician 1984; 30: 1835-9.. This finding possibly denotes greater clinical fragility of Brazilian adults with SCT exposed to malnutrition and infections.

As for the higher white blood cell count in Brazilian women with SCT aged between 18 and 59 years, when compared to those without SCT¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... identified by the UL, similar results were found in Nigeria, but in the SCD.²⁴24 Akinbami A, Dosunmu A, Adediran A, Oshinaike O, Adebola P, Arogundade O. Haematological values in homozygous sickle cell disease in steady state and haemoglobin phenotypes AA controls in Lagos, Nigeria. BMC Res Notes 2012; 5: 396. https://doi.org/10.1186/1756-0500-5-396
https://doi.org/10.1186/1756-0500-5-396... It is also worth mentioning that, in people with SCD, leukocytosis can occur due to autosplenectomy resulting from occlusion of splenic vessels, increasing vulnerability to infections²⁴24 Akinbami A, Dosunmu A, Adediran A, Oshinaike O, Adebola P, Arogundade O. Haematological values in homozygous sickle cell disease in steady state and haemoglobin phenotypes AA controls in Lagos, Nigeria. BMC Res Notes 2012; 5: 396. https://doi.org/10.1186/1756-0500-5-396
https://doi.org/10.1186/1756-0500-5-396... . Leukocytosis in SCD indicates a poor prognosis, being a risk factor for early death, stroke and acute chest syndrome, while a reduction in neutrophil counts is associated with a good prognosis²⁴24 Akinbami A, Dosunmu A, Adediran A, Oshinaike O, Adebola P, Arogundade O. Haematological values in homozygous sickle cell disease in steady state and haemoglobin phenotypes AA controls in Lagos, Nigeria. BMC Res Notes 2012; 5: 396. https://doi.org/10.1186/1756-0500-5-396
https://doi.org/10.1186/1756-0500-5-396... . There is evidence to suggest that the phagocytic function of neutrophils may be reduced in individuals with SCD, implying that their phagocytic competence affects the clinical severity of the disease²⁴24 Akinbami A, Dosunmu A, Adediran A, Oshinaike O, Adebola P, Arogundade O. Haematological values in homozygous sickle cell disease in steady state and haemoglobin phenotypes AA controls in Lagos, Nigeria. BMC Res Notes 2012; 5: 396. https://doi.org/10.1186/1756-0500-5-396
https://doi.org/10.1186/1756-0500-5-396... ,³¹31 Okpala I. The intriguing contribution of white blood cells to sickle cell disease – a red cell disorder. Blood Rev 2004; 18(1): 65-73. https://doi.org/10.1016/s0268-960x(03)00037-7
https://doi.org/10.1016/s0268-960x(03)00... . All explanations lack empirical and theoretical evidence, so they need to be further investigated in adults with SCT.

As for the significant differences found in platelets, when stratified by sex and age, the highest mean values in women with SCT aged between 18 and 59 years compared to those without SCT¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... may stem from thrombocytosis, attributed to hemolytic anemia and autosplenectomy associated with SCD²⁴24 Akinbami A, Dosunmu A, Adediran A, Oshinaike O, Adebola P, Arogundade O. Haematological values in homozygous sickle cell disease in steady state and haemoglobin phenotypes AA controls in Lagos, Nigeria. BMC Res Notes 2012; 5: 396. https://doi.org/10.1186/1756-0500-5-396
https://doi.org/10.1186/1756-0500-5-396... ,³²32 Ahmed SG, Ibrahim UA, Hassan AW. Hematological parameters in sickle cell anemia patients with and without priapism. Ann Saudi Med 2006; 26(6): 439-43. https://doi.org/10.5144/0256-4947.2006.439
https://doi.org/10.5144/0256-4947.2006.4... . It is well established in the literature that thrombocytosis is associated with SCD and several types of anemia²⁴24 Akinbami A, Dosunmu A, Adediran A, Oshinaike O, Adebola P, Arogundade O. Haematological values in homozygous sickle cell disease in steady state and haemoglobin phenotypes AA controls in Lagos, Nigeria. BMC Res Notes 2012; 5: 396. https://doi.org/10.1186/1756-0500-5-396
https://doi.org/10.1186/1756-0500-5-396... ,³²32 Ahmed SG, Ibrahim UA, Hassan AW. Hematological parameters in sickle cell anemia patients with and without priapism. Ann Saudi Med 2006; 26(6): 439-43. https://doi.org/10.5144/0256-4947.2006.439
https://doi.org/10.5144/0256-4947.2006.4... . The lower mean levels of platelets in men with SCT compared to those without SCT¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... and aged between 18 and 59 years may result from alterations in components of hemostasis, including platelet function, procoagulant mechanisms, anticoagulants and the fibrinolytic system in SCD³³33 Stypulkowski JB, Manfredini V. Alterações hemostáticas em pacientes com doença falciforme. Rev Bras Hematol Hemoter 2010; 32(1): 1-7. https://doi.org/10.1590/S1516-84842010005000001
https://doi.org/10.1590/S1516-8484201000... . The hypercoagulable state present in people with HbS is related to qualitative changes in platelets³³33 Stypulkowski JB, Manfredini V. Alterações hemostáticas em pacientes com doença falciforme. Rev Bras Hematol Hemoter 2010; 32(1): 1-7. https://doi.org/10.1590/S1516-84842010005000001
https://doi.org/10.1590/S1516-8484201000... , which would possibly explain these findings.

The other hematological alterations found in adults with SCT compared to those without SCT¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... , in women aged between 18 and 59 years for eosinophils and monocytes, and hematocrit after 60 years old, as well as those found in men aged 18 to 59 years old for lymphocytes and hemoglobin, and hematocrit at 60 years or older, can be attributed to behavioral, genetic, nutritional, socioeconomic factors, as well as exposure to allergens, infections and parasitic loads³⁴34 Abbam G, Tandoh S, Tetteh M, Afrifah DA, Annani-Akollor ME, Owiredu EW, et al. Reference intervals for selected haematological and biochemical parameters among apparently healthy adults in different eco-geographical zones in Ghana. PLoS One 2021; 16(1): e0245585. https://doi.org/10.1371/journal.pone.0245585
https://doi.org/10.1371/journal.pone.024... .

In the present study, there were substantial differences in the hematological RI of Brazilian adults with and without SCT¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... according to skin color. Anemia identified by lower hemoglobin levels in brown adults with SCT compared to those without SCT¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... deserves to be investigated, given that conditions associated with anemia differ by ethnicity³⁵35 Zakai NA, McClure LA, Prineas R, Howard G, McClellan W, Holmes CE, et al. Correlates of anemia in American blacks and whites: the REGARDS Renal Ancillary Study. Am J Epidemiol 2009; 169(3): 355-64. https://doi.org/10.1093/aje/kwn355
https://doi.org/10.1093/aje/kwn355... . Although racial differences in hematological parameters may be due to heredity and chronic diseases, socioeconomic factors differ according to ethnicity as well³⁵35 Zakai NA, McClure LA, Prineas R, Howard G, McClellan W, Holmes CE, et al. Correlates of anemia in American blacks and whites: the REGARDS Renal Ancillary Study. Am J Epidemiol 2009; 169(3): 355-64. https://doi.org/10.1093/aje/kwn355
https://doi.org/10.1093/aje/kwn355... . The literature reports the lack of studies that explore racial differences in hematological parameters³⁵35 Zakai NA, McClure LA, Prineas R, Howard G, McClellan W, Holmes CE, et al. Correlates of anemia in American blacks and whites: the REGARDS Renal Ancillary Study. Am J Epidemiol 2009; 169(3): 355-64. https://doi.org/10.1093/aje/kwn355
https://doi.org/10.1093/aje/kwn355... . Black populations are underrepresented in epidemiological studies on the subject³⁵35 Zakai NA, McClure LA, Prineas R, Howard G, McClellan W, Holmes CE, et al. Correlates of anemia in American blacks and whites: the REGARDS Renal Ancillary Study. Am J Epidemiol 2009; 169(3): 355-64. https://doi.org/10.1093/aje/kwn355
https://doi.org/10.1093/aje/kwn355... , and we also identified the lack of investigations in the brown population. This is an important point of discussion, given that the Brazilian population is characterized by miscegenation, different ethnicities and social/economic segments¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... , which has implications for the epidemiology of SCT and SCD in the country³⁶36 Cavalcanti JM, Maio MC. Entre negros e miscigenados: a anemia e o traço falciforme no Brasil nas décadas de 1930 e 1940. Hist Cienc Saude-Manguinhos 2011; 18(2): 377-406. https://doi.org/10.1590/S0104-59702011000200007
https://doi.org/10.1590/S0104-5970201100... .

This study had limitations inherent to cross-sectional studies, such as the impossibility of establishing a causal relationship; some findings in blood count parameters may reflect lifestyle and treatment. However, the hematological profile of Brazilian patients with SCT has not been studied extensively in recent years, and this is the first study with this purpose. Given the representative sample of the Brazilian population, the generalization of results is relatively safe for national estimates. It was not possible to identify people with SCD due to unavailability in the PNS database; laboratory alterations may lead to underdiagnosis of SCD in the country. Thus, our results must be interpreted with caution. Furthermore, there is controversy in the literature whether SCT is a benign state or an intermediate phenotype of the disease, and at the same time, we lack studies on this condition and its complications, which could be underestimated³⁷37 Key NS, Derebail VK. Sickle-cell trait: novel clinical significance. Hematology Am Soc Hematol Educ Program 2010; 2010: 418-22. https://doi.org/10.1182/asheducation-2010.1.418
https://doi.org/10.1182/asheducation-201... . Evidence suggests that SCT may not be a completely benign state nor a disease, but a risk factor for adverse events resulting from the interaction between genetic and environmental influences³⁸38 Maciaszek JL, Lykotrafitis G. Sickle cell trait human erythrocytes are significantly stiffer than normal. J Biomech 2011; 44(4): 657-61. https://doi.org/10.1016/j.jbiomech.2010.11.008
https://doi.org/10.1016/j.jbiomech.2010.... .

This study showed differences between the RI of Brazilian adults with and without SCT¹⁴14 Rosenfeld LG, Malta DC, Szwarcwald CL, Bacal NS, Cuder MAM, Pereira CA, et al. Reference values for blood count laboratory tests in the Brazilian adult population, National Health Survey. Rev Bras Epidemiol 2019; 22Suppl 02(Suppl 02): E190003.SUPL.2. https://doi.org/10.1590/1980-549720190003.supl.2
https://doi.org/10.1590/1980-54972019000... . These results point out the importance of neonatal screening to identify SCT, genetic counseling and the need for research that characterizes the consequences and risks to health, to support the control and prevention of diseases. The detection of individuals with heterozygous hemoglobinopathies such as SCT is extremely relevant in terms of public health³⁹39 Orlando GM, Naoum PC, Siqueira FAM, Bonini-Domingos CR. Diagnóstico laboratorial de hemoglobinopatias em populações diferenciadas. Rev Bras Hematol Hemoter 2000; 22(2): 111-21. https://doi.org/10.1590/S1516-84842000000200007
https://doi.org/10.1590/S1516-8484200000... for its adequate management in Brazil.

ACKNOWLEDGMENTS:

We would like to acknowledge the National Council for Scientific and Technological Development (CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico) for granting a Junior Postdoctoral scholarship to Sá ACMGN and a productivity scholarship to Malta DC. Also, the Secretariat of Health Surveillance, for the support in TED 147/2018.

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