BACKGROUND:Immune thrombocytopenia is an immune disease characterized by thrombocytopenia and bleeding due to platelet antibodies against platelet membrane glycoproteins. Human platelet antigens are derived from polymorphisms of these glycoproteins. The aim of this study was to investigate human platelet antigen frequencies in immune thrombocytopenia patients from the state of Amazonas, Brazil and investigate the potential association between specific antigens and risk for immune thrombocytopenia.METHOD:Human platelet antigen typing was performed by BeadChip technology to determine allelic variants of 11 systems (HPA-1 to HPA-9, HPA-11 and HPA-15). Thirty-six patients (8 male and 28 female) with a median age of 34 years (range: 9-69 years) were evaluated and compared with data from Amazonas blood donors.RESULTS:Platelet counts varied from 3 to 98×109/L. The allele frequencies were 0.944 for HPA-1a, 0.056 for HPA-1b, 0.847 for HPA-2a, 0.153 for HPA-2b, 0.555 for HPA-3a, 0.444 for HPA-3b, 0.805 for HPA-5a, 0.222 for HPA-5b, 0.9975 for HPA-9a, 0.025 for HPA-9b, 0.486 for HPA-15a and 0.513 for HPA-15b. Among immune thrombocytopenia individuals, no b allele of the HPA-4, -6, -7, -8 and -11 were found.CONCLUSIONS:The results suggest HPA-1a, HPA-3b and HPA-5b are immune thrombocytopenia-specific autoepitopes.
OBJECTIVE:To review published data on oral manifestations of multiple myeloma. METHODS:An electronic database search was performed of articles published from 1971 to November 2016 in order to identify studies that reported oral manifestations of patients with multiple myeloma. Case reports and case series with oral manifestations of multiple myeloma in English were included in the study. An additional search was performed of the references of the selected articles. RESULTS:Thirty-seven articles that reported 81 patients with oral manifestations of multiple myeloma were selected: 30 case reports (82%) and seven case series (18%). The most common clinical features in the dental cavity were swelling (65.4%), bone pain (33.3%), paresthesia (27.1%) and amyloidosis lesions (11.1%). Osteolytic lesions detected on imaging exams were reported in the majority of the patients (90.1%) as plasmacytomas or 'punched-out' lesions. CONCLUSIONS:Swelling and osteolytic lesions represent the most common clinical and radiographic signs of the jaws relating to multiple myeloma, respectively.
BACKGROUND:Individuals with sickle cell anemia may suffer symptomatic or silent cerebral infarcts leading to neurocognitive complications. This study investigated the cognitive and intellectual performance of children and adolescents with sickle cell anemia.METHODS:The socioeconomic status, clinical aspects and behavioral profile of 15 young individuals with sickle cell anemia were evaluated. The Wechsler Intelligence Scale for Children, the Developmental Neuropsychological Assessment Test, and the Child Behavior Checklist were applied.RESULTS:Participants with a history of stroke had lower intelligence quotient (IQ) scores. Alterations were found in attention and executive functioning, language, verbal and visual memory, visuospatial processing and sensorimotor skills. These alterations were found both in the children and adolescents who had had a cerebral infarction and in those who apparently had not. In the majority of cases, there were learning difficulties, a history of repeating school years and a need for specialist educational support. The most common additional diagnoses in accordance with the Diagnostic and Statistical Manual of Mental Disorders IV were depressive disorder, anxiety disorder and somatic disorder, as well as conditions associated with physical and psychosocial repercussions of sickle cell anemia.CONCLUSION:As sickle cell anemia is considered a progressive cerebral vasculopathy, it is a potential risk factor for neurocognitive and psychosocial development. Therefore, periodic neuropsychological and behavioral evaluations of children and adolescents with sickle cell anemia may represent a useful measure to reduce long-term biopsychosocial repercussions.
Introduction: Pre-transfusion tests, essential for the release of blood components, may be affected by drugs. Monoclonal antibodies represent a class of medications increasingly used in the clinical practice, with anti-CD38 monoclonal antibodies (daratumumab) being a promising resource in the treatment of refractory myeloma. This monoclonal antibody recognizes CD38 in myeloma cells and interferes with pre-transfusion tests by causing panreactivity in indirect antiglobulin tests thereby clinically masking alloantibodies. Dithiothreitol is a reagent that breaks disulfide bonds and effectively destroys antigenic sites for CD38 on red blood cells. This study reports the immunohematological findings of pre-transfusion tests of patients with multiple myeloma receiving daratumumab and on solutions to prevent the interference of this monoclonal antibody. Methods: Serum samples from five patients on anti-CD38 monoclonal antibody treatment were evaluated. Tests performed included ABO/RhD typing, indirect antiglobulin test, direct antiglobulin test and eluate test. A daily evaluation was performed to determine the shelf life of dithiothreitol-treated red blood cells when stored in Alsever's solution. Results: No interference in the ABO/RhD typing results was noted but in all samples, a panreactivity was observed in indirect antiglobulin tests. Regarding the direct antiglobulin test, two samples presented positive results but negative eluates. In all samples, treatment of reagent red blood cells with 0.2 M dithiothreitol offset interference by anti-CD38 monoclonal antibodies. Dithiothreitol-treated red blood cells stored in Alsever's solution were stable for up to 15 days. Conclusion: Treatment of reagent red blood cells with dithiothreitol can be efficient and accessible to offset the interference of the anti-CD38 drug in pre-transfusion tests. The number of costly serological workups can be reduced by having stored dithiothreitol red blood cells with this proving to be a useful reagent for investigating anti-CD38. (C) 2017 Associacao Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda.
BACKGROUND:Due to laboratory logistic issues, our center has traditionally scheduled peripheral blood stem cell harvests based on timing from the start of mobilization. This has proved to be useful in some cases, but also resulted in many fruitless harvests due to poor mobilization. In order to improve the efficiency of collections and compare the effectiveness of peripheral blood CD34+ cells as a predictor with data from other reports, this study analyzed the implementation of this routine. METHODS:Peripheral blood and leukapheresis samples were quantified by flow cytometry and the association between these parameters was assessed. RESULTS:Sixty-six consecutive leukapheresis samples were collected from 34 patients after the collection of peripheral blood samples for CD34+ quantification. A moderate positive correlation was observed between peripheral blood CD34+ cell count and total CD34+ cell count/kg (r = 0.596; p-value < 0.001). A multivariable regression model also confirmed this association and allowed the estimation that for every increase in five CD34+ cells/μL in the peripheral blood, a mean increase of 0.38 × 106 CD34+ cells/kg could be predicted. Demographic characteristics, baseline comorbidities and mobilization regimen did not influence final CD34+ cell count in this sample. CONCLUSIONS:As observed in other centers, quantification of peripheral blood CD34+ progenitor cells is a strong predictor of effectiveness to guide stem cell harvesting. Due to the results of this study, a modification in the peripheral blood stem cell harvesting logistics was implemented at our center in order to incorporate this routine.
BACKGROUND:The aim of this study was to evaluate the prevalence of pre-sarcopenia and bone mineral density after hematopoietic stem cell transplantation.METHODS:The study group consisted of over 18-year-old patients who had been submitted to allogeneic transplantation at least one year previously. Patients and healthy controls were matched by sex, ethnic background, age, and body mass index. Body composition and bone mineral density were measured by dual-energy X-ray absorptiometry. A 24-h food recall and food frequency survey were performed. The biochemical evaluation included calcium, parathormone and vitamin D. Eighty-seven patients (52 men; age: 37.2±12.7 years; body mass index: 25±4.5kg/m2) were compared to 68 controls [31 men; age 35.4±15.5 years (p=0.467); body mass index 25.05±3.7kg/m2 (p=0.927)].RESULTS:There was no significant difference in the dietary intake between patients and controls. The mean levels of vitamin D were 23.5±10.3ng/mL; 29 patients (41.0%) had insufficient and 26 (37.14%) deficient levels. A higher prevalence of reduced bone mineral density was observed in 24 patients (25%) compared to 12 controls (19.1% - p<0.001). Pre-sarcopenia was diagnosed in 14 (14.4%) patients and none of the controls (p=0.05). There was a higher prevalence of pre-sarcopenia (66%) in patients with grades III and IV compared to those with grades 0-II graft-versus-host disease (10.9%) (p=0.004).CONCLUSION:patients submitted to transplantation had a higher prevalence of pre-sarcopenia and greater changes in bone mineral density compared to controls; the severity of graft-versus-host disease had an impact on the prevalence of pre-sarcopenia.
OBJECTIVE:To determine the mortality rate of children, adolescents and adults with sickle cell anemia in Rio de Janeiro, Brazil. METHODS:The number of deaths, the mortality rate and the causes of deaths in patients with sickle cell anemia who were treated and followed up at our institution for 15 years were determined and compared to data available for the Brazilian population. RESULTS:The overall number of deaths was 281 patients with a mortality rate of 16.77%. Survival probability was significantly higher in females. The number of deaths and the mortality rate were age-specific with a significant increase in the 19- to 29-year-old age group. The remaining life expectancy of the patients with sickle cell anemia was less than that of Brazilians at large. The gap between the two was about 20 years for ages between one and five years with this gap decreasing to ten years after the age of 65 years. The most common causes of death were infection, acute chest syndrome, overt stroke, organ damage and sudden death during painful crises. CONCLUSION:To the best of our knowledge, this is the first Brazilian study in a single institution in Rio de Janeiro; the mortality rate was 18.87% among adult patients with sickle cell anemia. The mortality rates in children and adults are higher than those reported in developed countries of the northern hemisphere.
Introduction: Prophylaxis is the treatment of choice for patients with severe hemophilia. Low adherence may limit the effectiveness of the prophylactic regimen, thereby compromising outcomes. Objective: The objective of this study was to validate the Brazilian version of the VERITAS-Pro prophylaxis adherence scale, originally an American questionnaire that can be answered by the individual responsible for prophylaxis as well as by an observer. Methods: The scale has 24 questions divided into six subscales: Routine, Dosage, Plan, Remember, Skip and Communicate. Participants were recruited at a blood center in southeastern Brazil for validation and reliability analyses. Validation measures included the results obtained using analog visual scales of adherence, interval between medication dispensed by the treatment center pharmacy and the percentage of recommended doses administered and infusions registered in the patients' logs. Results: The study included 32 individuals responsible for prophylaxis and five observers. The internal consistency was very good for the VERITAS-Pro total score, excellent for the Remember, Skip and Communicate subscales, good for the Dosage subscale, and acceptable for the Routine and Plan subscales. Twelve participants answered the questionnaire on more than one occasion to evaluate reproducibility. The intraclass correlation coefficient was excellent. Regarding convergent validity, the VERITAS-Pro scores were moderately correlated with the global adherence scale and with infusion log records, but showed a weak correlation with pharmacy dispensation records. Conclusion: The Brazilian version of VERITAS-Pro is a valid and reliable instrument, enabling the understanding of specific factors related to non-adherence and allowing targeted interventions for proper treatment. (C) 2017 Published by Elsevier Editora Ltda. on behalf of Associacao Brasileira de Hematologia, Hemoterapia e Terapia Celular.
Background: Pyruvate kinase deficiency is a hereditary disease that affects the glycolytic pathway of the red blood cell, causing nonspherocytic hemolytic anemia. The disease is transmitted as an autosomal recessive trait and shows a marked variability in clinical expression. This study reports on the molecular characterization of ten Brazilian pyruvate kinase- deficient patients and the genotype-phenotype correlations. Method: Sanger sequencing and in silico analysis were carried out to identify and characterize the genetic mutations. A non-affected group of Brazilian individuals were also screened for the most commonly reported variants (c.1456C>T and c.1529G>A). Results: Ten different variants were identified in the PKLR gene, of which three are reported here for the first time: p.Leu61Gln, p.Ala137Val and p.Ala428Thr. All the three missense variants involve conserved amino acids, providing a rationale for the observed enzyme deficiency. The allelic frequency of c.1456C>T was 0.1% and the 1529G>A variant was not found. Conclusion: This is the first comprehensive report on molecular characterization of pyruvate kinase deficiency from South America. The results allowed us to correlate the severity of the clinical phenotype with the identified variants. (C) 2017 Associacao Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda.
OBJECTIVE:To evaluate factors predictive for relapse in a cohort of adult patients with acute promyelocytic leukemia monitored by molecular methods during consolidation and during at least one month of maintenance therapy.METHODS:The charts and laboratory data of 65 adult patients with acute promyelocytic leukemia treated according to the International Consortium on Acute Promyelocytic Leukemia 2006 protocol were reviewed. The identification of the promyelocytic leukemia-retinoic acid receptor-alpha gene rearrangement at diagnosis, post-induction, post-consolidation and during maintenance treatment was performed by qualitative and quantitative reverse transcription polymerase chain reaction.RESULTS:Eighty-nine patients were diagnosed with acute promyelocytic leukemia over a seven-year period and of these 65 were eligible for treatment with the protocol. Among the 45 patients who received consolidation and maintenance treatment, six (13%) relapsed, three of whom presented hematologic and three presented molecular relapse. The first relapses occurred at a median of 39 months. Relapsed patients were from all risk groups (low, intermediate and high) and both morphological types (M3 and M3variant) were found. Three of these patients are alive and in molecular remission after salvage treatment. There were no statistically significant differences regarding gender, age, risk group, morphology, promyelocytic leukemia breakpoint cluster region, use of all-trans retinoic acid, development of differentiation syndrome and number of days to complete remission between the patients who relapsed and those who did not.CONCLUSION:Our results reinforce the importance of prolonged monitoring of acute promyelocytic leukemia patients using molecular methods to detect relapse early.
