Resumo em Inglês:

Objective: The aim of this study was to evaluate the effectiveness of mature red cell and reticulocyte parameters to identify three conditions: iron deficiency anemia, anemia of chronic disease, and anemia of chronic disease associated with absolute iron deficiency. Methods: Peripheral blood cells from 117 adult patients with anemia were classified accord- ing to iron status, inflammation, and hemoglobinopathies as: iron deficiency anemia (n = 42), anemia of chronic disease (n = 28), anemia of chronic disease associated with iron deficiency anemia (n = 22), and heterozygous β-thalassemia (n = 25). The percentage of microcytic eryth-rocytes, hypochromic erythrocytes, and the levels of hemoglobin in both reticulocytes and mature red cells were determined. Receiver operating characteristic analysis was used to evaluate the accuracy of the parameters in differentiating anemia. Results: There was no difference between the groups of iron deficiency and anemia of chronic disease associated with absolute iron deficiency for any of the parameters. The percentage of hypochromic erythrocytes was the best parameter to identify absolute iron deficiency in patients with anemia of chronic disease (area under curve = 0.785; 95% confidence interval: 0.661-0.909 with sensitivity of 72.7%, and specificity of 70.4%; cut-off value 1.8%). The formula microcytic erythrocyte count minus hypochromic erythrocyte count was very accurate to differentiate iron deficiency anemia from heterozygous β-thalassemia (area under curve = 0.977; 95% confidence interval: 0.950-1.005 with a sensitivity of 96.2%, and specificity of 92.7%; cut-off value 13.8). Conclusion: The erythrocyte and reticulocyte indices are moderately good to identify absolute iron deficiency in patients with anemia of chronic disease.

Resumo em Inglês:

Objective: To compare the effect of aquatic and land-based physiotherapy in reducing musculoskeletal hip and lower back pain and increasing overall physical capabilities of sickle cell disease patients. Methods: Informed written consent was obtained from all volunteers who were submitted to evaluations using different functional scales: Lequesne's Algofunctional Questionnaire and Oswestry Disability Index, trunk and hip range of motion, goniometry, trunk and hip muscle strength assessment using load cell, and surface electromyography of the iliocostalis, long dorsal (longissimus), gluteus maximus, gluteus medius and tensor fasciae latae muscles. Ten patients were randomized into two groups: aquatic physiotherapy with a mean age of 42 years (range: 25-67) and conventional physiotherapy with a mean age of 49 years (range: 43-59). Both groups were submitted to a twelve-week program of two sessions weekly. Results: After the intervention, significant improvements were observed regarding the Lequesne index (p-value = 0.0217), Oswestry Disability Index (p-value = 0.0112), range of motion of trunk extension (p-value = 0.0320), trunk flexion muscle strength (p-value = 0.0459), hip extension and abduction muscle strength (p-value = 0.0062 and p-value = 0.0257, respec- tively). Range of motion of trunk and hip flexion, extension, adduction and abduction, trunk extensor muscle strength and all surface electromyography variables showed no significant statistical difference. Conclusion: Physical therapy is efficient to treat musculoskeletal dysfunctions in sickle cell disease patients, irrespective of the technique; however, aquatic therapy showed a trend toward improvement in muscle strength. Further studies with a larger patient sample and longer periods of therapy are necessary to confirm these results.

Resumo em Inglês:

Background: Paroxysmal nocturnal hemoglobinuria is an acquired chronic hemolytic ane- mia, which often manifests as peripheral blood cytopenias and thrombosis. Objective: The aim of this study is to describe a Brazilian population of paroxysmal nocturnal hemoglobinuria patients. Methods: One hundred and three paroxysmal nocturnal hemoglobinuria cases were retrospectively reviewed and the clinical presentation, thrombosis, survival, and clone size were assessed. Diagnosis was established by flow cytometry. Results: Fifty-two male and 51 female patients with a median age of 24.1 years (5.5-62 years) were studied. Clinical symptoms included hemoglobinuria (18.4%), infection (46.6%) and thrombosis (16.5%), and 80.6% had pancytopenia. Patients were classified as classic parox- ysmal nocturnal hemoglobinuria (10), paroxysmal nocturnal hemoglobinuria with aplastic anemia (39), and paroxysmal nocturnal hemoglobinuria with subclinical features and aplas- tic anemia (54). There were significant differences in terms of median age, size of clone, clinical symptoms, and peripheral blood cell counts between the three subcategories. The clone size in erythrocytes and granulocytes were respectively 0.04% (range: 0-18%) and 7.3% (range: 0.3-68.7%) in patients with subclinical features and aplastic anemia, 15.8% (range: 0-99.7%) and 63.0% (range: 1.7-99.8%) in patients with aplastic anemia alone, and 82.2% (range: 0-99.85%) and 98.0% (81.3-100.0%) in Classic disease. Statistical differences were identified for platelets (p-value = 0.001), lactate dehydrogenase (p-value = 0.002) and the clone size (p-value < 0.001) in patients who suffered thrombotic events compared to those who did not. Overall survival was 81.7%, with patients with subclinical features and aplastic anemia having lower overall survival (76.5%). Conclusion: This retrospective review of 103 patients over an 11-year period represents the largest collection of paroxysmal nocturnal hemoglobinuria cases from a single center in Brazil. Flow cytometry showed that a larger clone was associated with classical symptoms and increased risk of thrombosis, even in patients with bone marrow failure, whereas a smaller clone was associated with bone marrow aplasia.

Resumo em Inglês:

Studies evaluating circulating endothelial cells by flow cytometry are faced by a lack of con- sensus about the best combination of monoclonal antibodies to be used. The rarity of these cells in peripheral blood, which represent 0.01% of mononuclear cells, drastically increases this challenge. Objective: The aim of this study is to suggest some combinations of markers that would safely and properly identify these cells. Methods: Flow cytometry analysis of circulating endothelial cells was performed applying three different panels composed of different combinations of the CD144, CD146, CD31, CD133, CD45 and anti-Vascular endothelial growth factor receptor-2 antibodies. Results: In spite of the rarity of the events, they were detectable and presented similar interperson numbers of circulating endothelial cells. Conclusion: The combination of markers successfully identified the circulating endothelial cells in healthy individuals, with the use of three different panels confirming the obtained data as reliable.

Resumo em Inglês:

Background: Brazil has a multiethnic population with a high diversity of hemoglobinopathies. While screenings for beta-globin mutations are far more common, alterations affecting alpha-globin genes are usually more silent and less well known. The aim of this study was to describe the results of a screening program for alpha-globin gene mutations in a representative sample of the Southeastern Brazilian population. Methods: A total of 135,000 individuals, including patients with clinical suspicion of hemoglobinopathies and their family members, randomly chosen individuals submitted to blood tests and blood donors who were abnormal hemoglobin carriers were analyzed. The variants were screened by alkaline and acid electrophoreses, isoelectric focusing and cation-exchange high performance liquid chromatography (HPLC) and the abnormal chains were investigated by reverse-phase high performance liquid chromatography (RP-HPLC). Mutations were identified by molecular analyses, and the oxygen affinity, heme-heme cooperativity and Bohr effect of the variants were evaluated by functional tests. Results: Four new and 22 rare variants were detected in 98 families. Some of these variants were found in co-inheritance with other hemoglobinopathies. Of the rare hemoglobins, Hasharon, Stanleyville II and J-Rovigo were the most common, the first two being S-like and associated with alpha-thalassemia. Conclusion: The variability of alpha-globin alterations reflects the high degree of racial miscegenation and an intense internal migratory flow between different Brazilian regions. This diversity highlights the importance of programs for diagnosing hemoglobinopathies and preventing combinations that may lead to important clinical manifestations in multiethnic populations.

Resumo em Inglês:

Objective: Myeloid neoplasms are heterogeneous diseases that are more incident in the elderly. The goals of this study were to aggregate a geriatric approach to the patient assessment, to show the impact of gender, age, hemoglobin concentration and comorbidities on the functionality of elderly with myeloid neoplasms and to better understand how the instruments of functional assessment work according to the aggressiveness of the disease. Methods: Elderly patients (≥60 years old) with myeloid neoplasms were assessed using the Karnofsky scale, Eastern Cooperative Oncologic Group scale, and basic and instru- mental activities of daily living scales. The hematopoietic cell transplantation-comorbidity index assessed the comorbidities. A mixed logistical regression model was fitted to estimate the impact of gender, age, hemoglobin concentration and the hematopoietic cell transplantation-comorbidity index on patients' functionality. Results: Eighty-two patients with a mean age of 72.8 years (range: 60-92 years) were evaluated. Eighty percent had good Karnofsky and Eastern Cooperative Oncologic Group scales and 39% were independent according to the daily living activity scales. All of the patients with poor Karnofsky and Eastern Cooperative Oncologic Group scales were classified as dependent by the daily living activity scales. The mixed logistic regression models showed that age, gender, hemoglobin concentration and the comorbidity index impacted on the daily living activity scales. Karnofsky and Eastern Cooperative Oncologic Group scales were affected by hemoglobin and the comorbidity index. The model hypothesized the hemoglobin concentration at which there was a higher risk of poor Karnofsky and Eastern Cooperative Oncologic Group scales. This hemoglobin concentration depended on comorbidities and on the aggressiveness of the myeloid neoplasm. Conclusion: The geriatric approach improved the sensitivity and specificity of the patients' assessment. Hemoglobin concentration associated to the risk of poor Karnofsky and Eastern Cooperative Oncologic Group scales depended on the comorbidity score and on the disease aggressiveness. The Karnofsky and Eastern Cooperative Oncologic Group scales had higher sensitivity in patients with more aggressive diseases.

Resumo em Inglês:

Objective: To study systemic lupus erythematosus in a Brazilian population using the American College of Rheumatology hematological classification criteria and report associations of the disease with serological and clinical profiles. Methods: This is a retrospective study of 460 systemic lupus erythematosus patients followed in a single rheumatologic center during the last 10 years. Hematological manifestations considered for this study were hemolysis, leukopenia, lymphocytopenia and thrombocytopenia. Results: The cumulative prevalences of leukopenia, thrombocytopenia, lymphocytopenia and hemolytic anemia were 29.8%, 21.08%, 17.7% and 8.4%, respectively. A higher percentage of patients with hemolysis had anticardiolipin IgM (p-value = 0.002). Those with leukopenia had more lymphopenia (p-value = 0.02), psychosis (p-value = 0.01), thrombocy- topenia (p-value <0.0001) and anti-double stranded DNA antibodies (p-value = 0.03). Patients with lymphopenia had more leukopenia (OR = 1.8; 95% CI = 1.01-3.29) and lupus anticoagulant antibodies (OR = 2.2; 95% CI = 1.16-4.39) and those with thrombocytopenia had more leukopenia (OR = 3.1; 95% CI = 1.82-5.44) and antiphospholipid syndrome (OR = 3.1; 95% CI = 1.28-7.87). Conclusion: The most common hematological finding was leukopenia and the least common was hemolysis. Associations of low platelet count and hemolysis were found with antiphospholipid syndrome and anticardiolipin IgM positivity, respectively. Leukopenia and lymphocytopenia are correlated and leukopenia is more common in systemic lupus erythe- matosus patients with psychosis, thrombocytopenia and anti-double stranded DNA.

Resumo em Inglês:

This review discusses hemoglobin D-Punjab, also known as hemoglobin D-Los Angeles, one of the most common hemoglobin variants worldwide. It is derived from a point mutation in the beta-globin gene (HBB: c.364G>C; rs33946267) prevalent in the Punjab region, North-western Indian. Hemoglobin D-Punjab can be inherited in heterozygosis with hemoglobin A causing no clinical or hematological alterations, or in homozygosis, the rarest form of inheritance, a condition that is commonly not related to clinical symptomatology. Moreover, this variant can exist in association with other hemoglobinopathies, such as thalassemias; the most noticeable clinical alterations occur when hemoglobin D-Punjab is associated to hemoglobin S. The clinical manifestations of this association can be similar to homozygosis for hemoglobin S. Although hemoglobin D-Punjab is a common variant globally with clinical importance especially in cases of double heterozygosis, hemoglobin S/D-Punjab is still understudied. In Brazil, for example, hemoglobin D-Punjab is the third most common hemoglobin variant. Thus, this paper summarizes information about the origin, geographic distribution, characterization and occurrence of hemoglobin D-Punjab haplotypes to try to improve our knowledge of this variant. Moreover, a list of the main techniques used in its identification is provided emphasizing the importance of complementary molecular analysis for accurate diagnosis.