Consensus of the Brazilian association of hematology, hemotherapy and cellular therapy on patient blood management: History and scenario of patient blood management in the world and in Brazil.

Patient Blood Management (PBM) is a multidimensional approach that seeks to optimize the use of blood and its components in patients. This matter emerged as a response to the need to reduce unnecessary exposure to blood transfusions and their potential risks. In the past, blood transfusion was often overused resulting in complications and high costs. The advent of Patient Blood Management has caused a paradigm shift, highlighting anemia prevention, bleeding control and maximizing the production of blood cells by the organism itself. Patient Blood Management guidelines include the early identification of anemia, strategies to minimize blood loss during surgery, intraoperative blood conservation techniques, preoperative hemoglobin optimization and evidence-based approaches to the rational use of blood transfusions. Aiming to improve clinical outcomes, decrease transfusion-related complications and reduce associated costs, this multidisciplinary approach counts on doctors, nurses, pharmacists and other healthcare professionals. Based on research and clinical evidence, Patient Blood Management continues to evolve thereby promoting safer, more effective patient-centered practices. Its implementation has proven beneficial in various medical contexts thereby contributing to improvements in the quality of care provided to patients. Our goal with this Consensus is to present readers with a broad and diverse view of Patient Blood Management so that they have the building blocks to implement this new technique.

Targeting patient blood management's first pillar: A multicentric retrospective study on preoperative anemia

ABSTRACT Introduction: Anemia is a common issue in surgical patients and has been associated with worse clinical outcomes, such as a higher probability of transfusions and longer hospital stay. Therefore, Patient Blood Management programs are actively aiming to achieve early identification and treatment of anemia, previous to the surgery. Methods and materials: In this study, preoperative hemoglobin within the Blood Order Schedule (BOS) at 16 blood centers in several Brazilian regions were retrospectively evaluated. Data regarding hemoglobin, age, gender and Brazilian regions were further analyzed. Results: From the 20,201 BOSs evaluated, the mean age was 55.65 ± 23.52 years old, with an overall prevalence of preoperative anemia of 60.9%. Women had a lower mean preoperative hemoglobin (11.74 ± 2.84 for women and 12.27 ± 3.06 for men) and higher prevalence of anemia than men (66% of females and 52.2% of males). The individuals over 65 years old and under 18 were the most affected by preoperative anemia. All regions had a high prevalence of preoperative anemia, without any direct association with the Human Development Index. Conclusion: In summary, upon evaluating the BOS, our study showed a high prevalence of preoperative anemia in all Brazilian regions, regardless of the gender and age group, but that women and individuals less than 18 or over 65 years old have an even higher prevalence of preoperative anemia. This information can identify the institutions in which preoperative anemia is a critical issue and in which new strategies, such as preoperative screening clinics, might be helpful.

Chagas disease: Performance analysis of immunodiagnostic tests anti-Trypanosoma cruzi in blood donors with inconclusive screening results

ABSTRACT Background: The screening of Trypanosoma cruzi-infected blood donors using two serological techniques frequently leads to conflicting results. This fact prompted us to evaluate the diagnostic performance of four "in-house" immunodiagnostic tests and two commercially available enzyme-linked immunosorbent assays (ELISAs). Material and Methods: One hundred and seventy-nine blood donors, whose screening for Chagas disease was doubtful, underwent three in-house ELISAs, one in-house immunoblotting test (TESA-blot), and two commercial ELISAs (bioMérieux and Wiener) in an attempt to define the presence or absence of infection. Simultaneously, 29 donors with previous positive results from three conventional serological tests and 30 donors with constant negative results were evaluated. Results: The ELISA-Wiener showed the highest rate in sensitivity (98.92%) and the ELISA-bioMérieux, the highest specificity (99.45%), followed by the TESA-blot, which showed superior performance, with lower false-negative (2.18%) and false-positive (1.12%) rates. In series, the combination composed of the TESA-blot and ELISA-bioMérieux showed slightly superior performance, with trifunctional protein deficiency (TFP) = 0.01%. Conclusion: Our study confirms the high sensitivity and specificity of commercial kits. To confirm the presence or absence of T. cruzi infection, the combination of TESA-blot and ELISA-bioMérieux may be suggested as the best alternative. Individually, the TESA-blot performed the closest to the gold standard; however, it is not commercially available.

Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular Consensus on genetically modified cells. V: Manufacture and quality control.

Chimeric antigen receptor T cells (CAR-T), especially against CD19 marker, present in lymphomas and acute B leukemia, enabled a revolution in the treatment of hematologic neoplastic diseases. The manufacture of CAR-T cells requires the adoption of GMP-compatible methods and it demands the collection of mononuclear cells from the patient (or from the donor), generally through the apheresis procedure, T cell selection, activation, transduction and expansion ex vivo, and finally storage, usually cryopreserved, until the moment of their use. An important aspect is the quality control testing of the final product, for example, the characterization of its identity and purity, tests to detect any contamination by microorganisms (bacteria, fungi, and mycoplasma) and its potency. The product thawing and intravenous infusion do not differ much from what is established for the hematopoietic progenitor cell product. After infusion, it is important to check for the presence and concentration of CAR-T cells in the patient's peripheral blood, as well as to monitor their clinical impact, for instance, the occurrence of short-term, such as cytokine release syndrome and neurological complications, and long-term complications, which require patient follow-up for many years.

Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular Consensus on genetically modified cells. VI: Accreditation process.

The adherence to accreditation programs proves the institutions' voluntary effort to pursue the quality and safety of their products and services by meeting internationally accepted standards audited by experts in the field, external to the service. Meeting such standards often exceeds domestic legal requirements. However, service providers are not released from complying with the legal requirements, both local and international, pertinent to the field. Accreditation programs use the precepts of the quality management system to validate and standardize processes, monitor results through quality control, proficiency testing, and indicators, and perform risk management. For cellular therapy services, the assessing agencies available in our field are the AABB/ABHH (American Association of Blood Banks/Brazilian Association of Hematology, Hemotherapy and Cellular Therapy) and FACT-JACIE (Foundation for the Accreditation of Cellular Therapy-Joint Accreditation Committee, ISCT/EBMT). Both agencies require that the accredited organization meets all the standards defined in each program. Applying services also have to establish and comply with a quality management standard that demonstrates procedural interrelationship to ensure product and service quality. This paper aims to concisely outline the essential features of those two accreditation programs, along with a brief overview of the accreditation process under each of them.

INCIDENCE OF SMALL FOR GESTATIONAL AGE NEONATES, ACCORDING TO THE FENTON AND INTERGROWTH-21ST CURVES IN A LEVEL II MATERNITY.

OBJECTIVE: To compare the incidence of small for gestational age infants among late preterm and term newborns, using the Fenton and Intergrowth-21st curves. METHODS: Observational and retrospective study with newborns in a level II maternity. The study was approved by the Institution's Ethics Committee. Live births from July 2007 to February 2009 with a gestational age from 34 to 41 weeks and seven days were included. Neonates with incomplete data were excluded. Appropriate weight for gestational age was assessed by the Fenton and Intergrowth-21st intrauterine growth curves, considering birth weight <10th percentile as small for gestational age. The degree of agreement between the two curves was assessed by the Kappa coefficient. Numerical variables were compared using the Student t-test or the Mann-Whitney. Categorical variables were compared using the chi-square test. Statistical analyzes were performed using SPSS17® software, considering significant, p<0.05. RESULTS: We included 2849 newborns with a birthweight of 3210±483 g, gestational age of 38.8±1.4 weeks; 51.1% male. The incidence of small for gestational age in the full sample was 13.0 vs. 8.7% (p<0.001, Kappa=0.667) by the Fenton and Intergrowth-21st curves, respectively. Among late preterm, the incidence of small neonates was 11.3 vs. 10.9% (p<0.001; Kappa=0.793) and among full-term infants it was 13.1% vs. 8.5% (p<0.001; Kappa=0.656), respectively for the Fenton and Intergrowth-21st curves. CONCLUSIONS: The incidence of small for gestational age newborns was significantly higher using the Fenton curve, with greater agreement between the Fenton and Intergrowth-21st curves among late preterm, compared to full term neonates.

Chagas disease: Performance analysis of immunodiagnostic tests anti-Trypanosoma cruzi in blood donors with inconclusive screening results.

BACKGROUND: The screening ofTrypanosoma cruzi-infected blood donors using two serological techniques frequently leads to conflicting results. This fact prompted us to evaluate the diagnostic performance of four "in-house" immunodiagnostic tests and two commercially available enzyme-linked immunosorbent assays (ELISAs). MATERIAL AND METHODS: One hundred and seventy-nine blood donors, whose screening for Chagas disease was doubtful, underwent three in-house ELISAs, one in-house immunoblotting test (TESA-blot), and two commercial ELISAs (bioMérieux and Wiener) in an attempt to define the presence or absence of infection. Simultaneously, 29 donors with previous positive results from three conventional serological tests and 30 donors with constant negative results were evaluated. RESULTS: The ELISA-Wiener showed the highest rate in sensitivity (98.92%) and the ELISA-bioMérieux, the highest specificity (99.45%), followed by the TESA-blot, which showed superior performance, with lower false-negative (2.18%) and false-positive (1.12%) rates. In series, the combination composed of the TESA-blot and ELISA-bioMérieux showed slightly superior performance, with trifunctional protein deficiency (TFP)=0.01%. CONCLUSION: Our study confirms the high sensitivity and specificity of commercial kits. To confirm the presence or absence of T. cruzi infection, the combination of TESA-blot and ELISA-bioMérieux may be suggested as the best alternative. Individually, the TESA-blot performed the closest to the gold standard; however, it is not commercially available.

Incidence of small for gestational age neonates, according to the fenton and intergrowth-21st curves in a level ii maternity / Incidência de recém-nascidos pequenos para a idade gestacional segundo curva de fenton e intergrowth-21st em uma maternidade de nível secundário

ABSTRACT Objective: To compare the incidence of small for gestational age infants among late preterm and term newborns, using the Fenton and Intergrowth-21st curves. Methods: Observational and retrospective study with newborns in a level II maternity. The study was approved by the Institution's Ethics Committee. Live births from July 2007 to February 2009 with a gestational age from 34 to 41 weeks and seven days were included. Neonates with incomplete data were excluded. Appropriate weight for gestational age was assessed by the Fenton and Intergrowth-21st intrauterine growth curves, considering birth weight <10th percentile as small for gestational age. The degree of agreement between the two curves was assessed by the Kappa coefficient. Numerical variables were compared using the Student t-test or the Mann-Whitney. Categorical variables were compared using the chi-square test. Statistical analyzes were performed using SPSS17® software, considering significant, p<0.05. Results: We included 2849 newborns with a birthweight of 3210±483 g, gestational age of 38.8±1.4 weeks; 51.1% male. The incidence of small for gestational age in the full sample was 13.0 vs. 8.7% (p<0.001, Kappa=0.667) by the Fenton and Intergrowth-21st curves, respectively. Among late preterm, the incidence of small neonates was 11.3 vs. 10.9% (p<0.001; Kappa=0.793) and among full-term infants it was 13.1% vs. 8.5% (p<0.001; Kappa=0.656), respectively for the Fenton and Intergrowth-21st curves. Conclusions: The incidence of small for gestational age newborns was significantly higher using the Fenton curve, with greater agreement between the Fenton and Intergrowth-21st curves among late preterm, compared to full term neonates.

RESUMO Objetivo: Comparar a incidência de neonatos pequenos para idade gestacional entre nascidos vivos pré-termo tardios e a termo utilizando as curvas de Fenton e Intergrowth-21st. Métodos: Estudo observacional retrospectivo com recém-nascidos de uma maternidade pública de nível secundário. Foram incluídos nascidos vivos de julho/2007 a fevereiro/2009 com idade gestacional de 34 a 41 semanas e seis dias. O estudo foi aprovado pelo Comitê de Ética da instituição. Foram excluídos recém-nascidos com dados incompletos. Para adequação do peso/da idade gestacional, utilizaram-se as curvas de crescimento intrauterino de Fenton e Intergrowth-21st, considerando-se pequeno aquele com peso ao nascer <10º percentil. O grau de concordância entre as duas curvas foi avaliado pelo coeficiente Kappa. As variáveis numéricas foram comparadas pelo teste t de Student ou de Mann-Whitney, conforme distribuição, e as categóricas pelo teste χ2. As análises estatísticas foram realizadas no programa Statistical Package for the Social Sciences (SPSS) 17®, considerando-se significante p<0,05. Resultados: Foram incluídos 2.849 recém-nascidos com peso ao nascer de 3210±483 g, idade gestacional de 38,8±1,4 semanas, sendo 51,1% masculinos. A incidência de recém-nascidos pequenos para a idade gestacional pela curva de Fenton e Intergrowth-21st na amostra total foi, respectivamente, de 13 e 8,7% (p<0,001; Kappa=0,667). Entre os pré-termo tardios, a incidência foi de 11,3 e 10,9% (p<0,001; Kappa=0,793) e entre os nascidos a termo foi de 13,1 e 8,5%, (p<0,001; Kappa=0,656), respectivamente, para as curvas de Fenton e Intergrowth-21st. Conclusões: A incidência de recém-nascidos pequenos para idade gestacional foi significantemente maior pela curva de Fenton, com maior concordância entre as curvas de Fenton e Intergrowth-21st em recém-nascidos pré-termo tardios do que nos nascidos a termo.

Associação brasileira de hematologia, hemoterapia e terapia celular consensus on genetically modified cells. V: manufacture and quality control

Chimeric antigen receptor T cells (CAR-T), especially against CD19 marker, present in lymphomas and acute B leukemia, enabled a revolution in the treatment of hematologic neoplastic diseases. The manufacture of CAR-T cells requires the adoption of GMP-compatible methods and it demands the collection of mononuclear cells from the patient (or from the donor), generally through the apheresis procedure, T cell selection, activation, transduction and expansion ex vivo, and finally storage, usually cryopreserved, until the moment of their use. An important aspect is the quality control testing of the final product, for example, the characterization of its identity and purity, tests to detect any contamination by microorganisms (bacteria, fungi, and mycoplasma) and its potency. The product thawing and intravenous infusion do not differ much from what is established for the hematopoietic progenitor cell product. After infusion, it is important to check for the presence and concentration of CAR-T cells in the patient's peripheral blood, as well as to monitor their clinical impact, for instance, the occurrence of short-term, such as cytokine release syndrome and neurological complications, and long-term complications, which require patient follow-up for many years.

Associação brasileira de hematologia, hemoterapia e terapia celular consensus on genetically modified cells. VI: accreditation process

The adherence to accreditation programs proves the institutions' voluntary effort to pursue the quality and safety of their products and services by meeting internationally accepted standards audited by experts in the field, external to the service. Meeting such standards often exceeds domestic legal requirements. However, service providers are not released from complying with the legal requirements, both local and international, pertinent to the field. Accreditation programs use the precepts of the quality management system to validate and standardize processes, monitor results through quality control, proficiency testing, and indicators, and perform risk management. For cellular therapy services, the assessing agencies available in our field are the AABB/ABHH (American Association of Blood Banks/Brazilian Association of Hematology, Hemotherapy and Cellular Therapy) and FACT-JACIE (Foundation for the Accreditation of Cellular Therapy-Joint Accreditation Committee, ISCT/EBMT). Both agencies require that the accredited organization meets all the standards defined in each program. Applying services also have to establish and comply with a quality management standard that demonstrates procedural interrelationship to ensure product and service quality. This paper aims to concisely outline the essential features of those two accreditation programs, along with a brief overview of the accreditation process under each of them.

BLOOD CELLS PROFILE IN UMBILICAL CORD OF LATE PRETERM AND TERM NEWBORNS.

OBJECTIVE: To describe the hematological profile in cord blood of late preterm and term newborns and compare blood indices according to sex, weight for gestational age and type of delivery. METHODS: Cross-sectional study with late preterm and term newborns in a second-level maternity. Multiple gestation, chorioamnionitis, maternal or fetal hemorrhage, suspected congenital infection, 5-minute Apgar <6, congenital malformations, and Rh hemolytic disease were excluded. Percentiles 3, 5,10, 25, 50, 75, 90, 95 and 97 of blood indices were calculated for both groups. RESULTS: 2,662 newborns were included in the sample, 51.1% males, 7.3% late preterms, 7.8% small for gestational age (SGA) and 81.2% adequate for gestational age (AGA). Mean gestational age was 35.6±1.9 and 39.3±1.0 weeks, respectively, for premature and term neonates. The erythrocytes indices and white blood cells increased from 34-36.9 to 37-41.9 weeks. Basophils and platelets remained constant during gestation. Premature neonates presented lower values ​​of all blood cells, except for lymphocytes and eosinophils. SGA neonates presented higher values ​​of hemoglobin, hematocrit and lower values of leukocytes, neutrophils, bands, segmented, eosinophils, monocytes and platelets. Male neonates presented similar values ​​of erythrocytes and hemoglobin and lower leukocytes, neutrophils, segmented and platelets. Neonates delivered by C-section had lower values ​​of red blood cells and platelets. Chronic or gestational hypertension induced lower number of platelets. CONCLUSIONS: Blood cells increased during gestation, except for platelets and basophils. SGA neonates had higher hemoglobin and hematocrit values and lower leukocytes. Number of platelets was smaller in male SGAs, born by C-section and whose mothers had hypertension.

Blood cells profile in umbilical cord of late preterm and term newborns / Perfil de hemograma em sangue de cordão umbilical de recém-nascidos pré-termo tardio e a termo

ABSTRACT Objective: To describe the hematological profile in cord blood of late preterm and term newborns and compare blood indices according to sex, weight for gestational age and type of delivery. Methods: Cross-sectional study with late preterm and term newborns in a second-level maternity. Multiple gestation, chorioamnionitis, maternal or fetal hemorrhage, suspected congenital infection, 5-minute Apgar <6, congenital malformations, and Rh hemolytic disease were excluded. Percentiles 3, 5,10, 25, 50, 75, 90, 95 and 97 of blood indices were calculated for both groups. Results: 2,662 newborns were included in the sample, 51.1% males, 7.3% late preterms, 7.8% small for gestational age (SGA) and 81.2% adequate for gestational age (AGA). Mean gestational age was 35.6±1.9 and 39.3±1.0 weeks, respectively, for premature and term neonates. The erythrocytes indices and white blood cells increased from 34-36.9 to 37-41.9 weeks. Basophils and platelets remained constant during gestation. Premature neonates presented lower values ​​of all blood cells, except for lymphocytes and eosinophils. SGA neonates presented higher values ​​of hemoglobin, hematocrit and lower values of leukocytes, neutrophils, bands, segmented, eosinophils, monocytes and platelets. Male neonates presented similar values ​​of erythrocytes and hemoglobin and lower leukocytes, neutrophils, segmented and platelets. Neonates delivered by C-section had lower values ​​of red blood cells and platelets. Chronic or gestational hypertension induced lower number of platelets. Conclusions: Blood cells increased during gestation, except for platelets and basophils. SGA neonates had higher hemoglobin and hematocrit values and lower leukocytes. Number of platelets was smaller in male SGAs, born by C-section and whose mothers had hypertension.

RESUMO Objetivo: Descrever o perfil hematológico em sangue de cordão de recém-nascidos pré-termo tardio e a termo e comparar parâmetros hematimétricos segundo sexo, adequação peso idade gestacional e tipo de parto. Métodos: Estudo transversal com recém-nascidos pré-termo tardio e a termo, em maternidade de nível secundário. Excluíram-se gestação múltipla, corioamnionite, hemorragia materna ou fetal, suspeita de infecção congênita, Apgar no 5o minuto <6, malformações congênitas e doença hemolítica Rh. Calcularam-se os percentis 3, 5, 10, 25, 50, 75, 90, 95 e 97 dos parâmetros hematológicos. Resultados: Incluíram-se 2.662 recém-nascidos, 51,1% do sexo masculino, 7,3% prematuros tardios, 7,8% pequenos para a idade gestacional e 81,2% adequados. A idade gestacional foi 35,6±1,9 e 39,3±1,0 semanas, respectivamente, nos prematuros e termos. As séries vermelha e branca aumentaram de 34-36,9 para 37-41,9 semanas, exceto basófilos e plaquetas, que permaneceram constantes. Os prematuros apresentaram menores médias nas séries vermelha, plaquetária e branca, com exceção de linfócitos e eosinófilos. Recém-nascidos pequenos para a idade gestacional apresentaram maiores valores de hemoglobina e hematócrito e menores de leucócitos, neutrófilos, bastonetes segmentados, eosinófilos, monócitos e plaquetas. Recém-nascidos masculinos apresentaram taxas semelhantes de hemoglobina e hematócrito e menores de leucócitos, neutrófilos, segmentados e plaquetas. Na cesárea, as células vermelhas e as plaquetas foram menores que no parto vaginal. O número de plaquetas foi menor na hipertensão crônica ou gestacional. Conclusões: As células sanguíneas aumentaram durante a gestação, exceto plaquetas e basófilos. Recém-nascidos pequenos para a idade gestacional apresentaram maiores taxas de hemoglobina e hematócrito e menores de células brancas. O número de plaquetas foi menor no recém-nascido pequeno para a idade gestacional, masculino, nascido por cesárea e de mãe hipertensa.

Molecular study of Cw /Cx antigens and frequency of Rh phenotypes in southeast Brazilian blood donors.

BACKGROUND: The Cw (RH:8), Cx (RH:9), and MAR (RH:51) antigens are encoded by alleles at the Cc locus of the Rh system, where Cw and Cx are considered low-frequency antigens and antithetical to the high-frequency antigen MAR. The frequency of Cw (RH:8) is approximately 2% in Caucasians, 1% in Black people, 4% in Finns, and 9% in Latvians. The aim of this study was to determine the frequency of RhD+ phenotypes in a population of southeast Brazilian blood donors and to perform a molecular study to distinguish the RHCE*Ce.08.01 and RHCE*Ce.09 alleles, responsible for the Cw and Cx expressions, respectively. METHODS: We investigated 11,536 RhD+ Brazilian blood donors. All samples were phenotyped for D, C, c, E, e, and Cw . In the Cw + samples, a molecular analysis was performed to detect the nucleotide substitutions A122G and G106A, which determine the Cw and Cx antigens, respectively. RESULTS: Cw antigen was found in 110 (0.95%) samples in the following phenotypes: DCw e/dCw e (72/0.62%), DCw e/DCw e (30/0.26%), and DCw e/DCw E (8/0.07%). Among 110 Cw + samples, 108 showed the A122G nucleotide substitution associated with RHCE*Ce.08.01 allele and 2 samples the G106A substitution associated with the RHCE*Ce.09.01 allele. CONCLUSION: This study showed the prevalence of the RhD+ phenotype in the Brazilian population, and that through the molecular study, it was possible to differentiate the RHCE*Ce.08.01 and RHCE*Ce.09.01 alleles. The phenotype frequency was similar from Black people (1%) and different from Caucasians, Finns, and Latvians.

Association between Knops blood group polymorphisms and susceptibility to malaria in an endemic area of the Brazilian Amazon

Complement receptor 1 (CR1) gene polymorphisms that are associated with Knops blood group antigens may influence the binding of Plasmodium parasites to erythrocytes, thereby affecting susceptibility to malaria. The aim of this study was to evaluate the genotype and allele and haplotype frequencies of single-nucleotide polymorphisms (SNPs) of Knops blood group antigens and examine their association with susceptibility to malaria in an endemic area of Brazil. One hundred and twenty-six individuals from the Brazilian Amazon were studied. The CR1-genomic fragment was amplified by PCR and six SNPs and haplotypes were identified after DNA sequence analysis. Allele and haplotype frequencies revealed that the Kn b allele and H8 haplotype were possibly associated with susceptibility to Plasmodium falciparum. The odds ratios were reasonably high, suggesting a potentially important association between two Knops blood antigens (Kn b and KAM+) that confer susceptibility to P. falciparum in individuals from the Brazilian Amazon.

Estudo do sistema de grupo sangüíneo Duffy em habitantes da região endêmica para malária e doadores de sangue / Study of the Duffy blood-group system in malarial endemic region inhabitants and blood donors

Objetivos: O presente estudo teve os seguintes objetivos: 1. Avaliar através de técnicas sorológicas, a freqüência dos fenótipos Fy(a+b+), Fy(a+b-), Fy(a-b+) e Fy(a-b-), do sistema de grupo sangüíneo Duffy, em habitantes de região endêmica para malária e doadores de sangue; 2. Avaliar através de técnicas de biologia molecular, a freqüência dos alelos FYA e FYB, do gene Duffy (FY), em habitantes de região endêmica para malária e doadores de sangue; 3. Avaliar através de técnica de biologia molecular, a freqüência da mutação molecular -33TC no "box" Gata-1 da região promotora do gene FY, caracterizando o alelo FYBes (eritróide silencioso) nos alelos FYB e FYA, em habitantes de região endêmica para malária e doadores de sangue; 4. Avaliar através de técnicas de biologia molecular, a freqüência das mutações moleculares C265T e G298A na região codificadora do FY, no alelo FYB, que caracterizam o ateio FYBfraco, em indivíduos que apresentaram discrepância entre o fenótipo e o genótipo, caracterizada pelo fenótipo Fy(a+b-) e o genótipo FYAIFFYB, em habitantes de região endêmica para malária e doadores de sangue; 5. Correlacionar a freqüência dos fenótipos Fy(a+b+), Fy(a+b-), Fy(a-b+) e Fy(a-b-) com o desenvolvimento de malária por Plasmodium vivax (P. vivax) em habitantes de região endêmica para malária; 6. Correlacionar a freqüência dos genótipos FYA/FFYA, FYA/FFYB e FYB/FFYB, com o desenvolvimento de malária por P. vívax em habitantes de região endêmica para malária; 7. Correlacionar a freqüência da mutação molecular –33TC no “box” Gata-1 da região promotora do gene FY com infecção pelo P. vivax em habitantes da região endêmica para malária; 8. Efetuar análise da seqüência de nucleotídeos dos indivíduos que apresentaram discrepância entre o fenótipo e o genótipo, caracterizada pelo fenótipo Fy(a+b-) e o genótipo FYA/FYB, em habitantes de região endêmica para malária e doadores de sangue…(au)