Time between inhibitor detection and start of immune tolerance induction: Association with outcome in the BrazIT study.

BACKGROUND: Immune tolerance induction (ITI) is the treatment of choice for eradication of anti-factor VIII (FVIII) neutralizing alloantibodies (inhibitors) in people with inherited hemophilia A and high-responding inhibitor (PwHA-HRi). The association between ITI outcome and time elapsed between inhibitor detection and start of ITI (∆tinhi-ITI ) is debatable. OBJECTIVE: The aim of this study was to evaluate this association among a large cohort of severe PwHA-HRi. METHODS: Severe (factor VIII activity level <1%) PwHA-HRi on ITI (n = 142) were enrolled in 15 hemophilia treatment centers. PwHA-HRi were treated according to the Brazilian ITI Protocol. ITI outcomes were defined as success (i.e., recovered responsiveness to exogenous FVIII) and failure (i.e., no responsiveness to exogenous FVIII and requirement of bypassing agents to control bleeding). RESULTS: Median ages at inhibitor detection and at ITI start were 3.2 years (interquartile range [IQR], 1.6-8.1) and 6.9 years [IQR, 2.6-20.1), respectively. PwHA-HRi were stratified according to ∆tinhi-ITI quartiles: first (0.0-0.6 year), second (>0.6-1.7 year), third (>1.7-9.2 years), and fourth quartile (>9.2-24.5 years). The overall success rate was 65.5% (93/142), with no difference among first, second, third, and fourth quartiles (62.9%, 69.4%, 58.3%, and 71.4%, respectively) even after adjusting the analyses for potential confounders. CONCLUSION: In conclusion, delayed ITI start is not associated with failure of ITI in PwHA-HRi. Therefore, ITI should be offered for these patients, regardless of the time elapsed between the detection of inhibitor and the ITI start.

Altered left ventricular twist is associated with clinical severity in adults and adolescents with homozygous sickle cell anemia.

BACKGROUND: Sickle cell anemia (SCA) is associated with cardiac abnormalities and premature death. The aims of this study were to identify early markers of cardiac dysfunction through ventricular strain and ventricular twist and determine the relationships between these measures and other markers of cardiovascular risk. METHODS: Forty patients with SCA (mean age, 23.5 ± 9.3 years; 24 male patients) and 40 age- and sex-matched healthy individuals were compared. All subjects participated in structured interviews, and blood samples were collected. Standard echocardiography with subsequent offline evaluations using left ventricular (LV) and right ventricular systolic strain and rotational analyses of the left ventricle using two-dimensional speckle-tracking echocardiography were performed. RESULTS: There were no differences in LV ejection fraction, global LV strain (longitudinal, circumferential, and radial), and global right ventricular longitudinal strain between patients and controls; however, LV twist was significantly lower in the patient group (mean, 7.4 ± 1.2° vs 10.7 ± 1.8°; P < .0001). Several variables were strongly related to LV twist, including the clinical severity index (ρ = -0.97, Z score = -6.05, P < .0001), E/e' ratio (r = 0.78, P < .0001), LV end-diastolic volume index (r = 0.81, P < .0001), and pulmonary artery systolic pressure (r = 0.72, P < .0001). CONCLUSIONS: LV twist is altered in patients with SCA. There were strong correlations between left ventricular twist and clinical severity index, E/e' ratio, LV end-diastolic volume index, and pulmonary artery systolic pressure. These data suggest that decreased LV twist may indicate a subgroup of patients with SCA at greater cardiac risk.

Altered Left Ventricular Twist Is Associatedwith Clinical Severity in Adults and Adolescentswith Homozygous Sickle Cell Anemia

Sickle cell anemia (SCA) is associated with cardiac abnormalities and premature death. The aimsof this study were to identify early markers of cardiac dysfunction through ventricular strain and ventriculartwist and determine the relationships between these measures and other markers of cardiovascular risk.Methods: Forty patients with SCA (mean age, 23.5 6 9.3 years; 24 male patients) and 40 age- and sexmatchedhealthy individuals were compared. All subjects participated in structured interviews, and bloodsamples were collected. Standard echocardiography with subsequent offline evaluations using left ventricular(LV) and right ventricular systolic strain and rotational analyses of the left ventricle using two-dimensionalspeckle-tracking echocardiography were performed.Results: There were no differences in LV ejection fraction, global LV strain (longitudinal, circumferential, andradial), and global right ventricular longitudinal strain between patients and controls; however, LV twist wassignificantly lower in the patient group (mean, 7.4 6 1.2 vs 10.7 6 1.8 ; P < .0001). Several variables werestrongly related to LV twist, including the clinical severity index (r = 0.97, Z score = 6.05, P < .0001), E/e0 ratio(r = 0.78, P < .0001), LV end-diastolic volume index (r = 0.81, P < .0001), and pulmonary artery systolic pressure(r = 0.72, P < .0001).Conclusions: LV twist is altered in patients with SCA. There were strong correlations between left ventriculartwist and clinical severity index, E/e0 ratio, LV end-diastolic volume index, and pulmonary artery systolic pressure.These data suggest that decreased LV twist may indicate a subgroup of patients with SCA at greatercardiac risk.

Echocardiography in thalassemic patients on blood transfusions and chelation without heart failure.

BACKGROUND: Patients with thalassemia major present chronic hemolysis and require regular blood transfusions which may cause iron overload cardiomyopathy and chronic heart failure. Hemochromatosis is characterized by excessive iron accumulation in tissues, and heart involvement is the main cause of death in patients with thalassemia. OBJECTIVE: The aim of this study was to evaluate cardiac structure and function by conventional Doppler echocardiography and tissue Doppler imaging in patients with TM and no clinical evidence of heart failure. METHODS: This is a prospective observational study including 18 patients with thalassemia major (TM) receiving regular blood transfusion. To separately evaluate anemia and blood transfusion effects, two gender, age, weight, and height-matched control groups were included: one with healthy individuals (Healthy, n=18) and one with iron deficient anemia patients (Anemia, n=18). Statistical analysis was performed using ANOVA followed by Tukey's test or Kruskal-Wallis's and Dunn's test. RESULTS: The following echocardiographic variables presented significantly higher values in TM than the Anemia and Healthy groups: left atrium volume index (Healthy: 16.4±6.08; Anemia: 17.9±7.02; TM: 24.1±8.30 cm³/m²); mitral septal E/Em ratio (Healthy: 6.55±1.60; Anemia: 6.74±0.74; TM: 8.10±1.31); and duration of reverse pulmonary vein flow [Healthy: 74.0 (59.0-74.0); Anemia: 70.5 (67.0-74.0); TM: 111 (87.0-120) ms]. The mitral E/A ratio was higher in TM than Anemia (Healthy: 1.80±0.40; Anemia: 1.80±0.24; TM: 2.03±0.34). No differences were found in left ventricular structures and systolic function indexes. CONCLUSION: Conventional Doppler echocardiography and tissue Doppler allow changes in left ventricular diastolic function to be identified in asymptomatic patients with thalassemia major.

Ecocardiografia de pacientes talassêmicos sem insuficiência cardíaca em tratamento com transfusões sanguíneas e quelação / Echocardiography in thalassemic patients on blood transfusions and chelation without heart failure

FUNDAMENTO: Pacientes com talassemia major (TM) apresentam hemólise crônica e necessitam de transfusões sanguíneas egularmente que podem causar cardiomiopatia por sobrecarga de ferro e insuficiência cardíaca crônica. A hemocromatose é caracterizada por acúmulo excessivo de ferro nos tecidos; acometimento do coração é a principal causa de óbito em pacientes com talassemia. OBJETIVO: Avaliar as estruturas e a função cardíaca por meio de ecocardiografia com Doppler convencional e Doppler tecidual em pacientes com TM, sem evidência clínica de insuficiência cardíaca. MÉTODOS: Trata-se de estudo observacional prospectivo de 18 pacientes com TM que recebem transfusão sanguínea regularmente. Para avaliar, separadamente, os efeitos da anemia e da transfusão sanguínea, dois grupos controles pareados por gênero, idade, peso e altura foram incluídos: um com indivíduos saudáveis (Saudável, n = 18) e outro com pacientes com anemia por deficiência de ferro (Anemia, n = 18). Análise estatística foi realizada utilizando ANOVA seguida pelo teste de Tukey ou Kruskal-Wallis e teste de Dunn. RESULTADOS: As seguintes variáveis ecocardiográficas apresentaram valores significativamente mais elevados no grupo TM do que nos grupos Anemia e Saudável: índice de volume do átrio esquerdo (Saudável: 16,4 ± 6,08; Anemia: 17,9 ± 7,02; TM: 24,1 ± 8,30 cm/m); razão E/Em septal mitral (Saudável: 6,55 ± 1,60; Anemia: 6,74 ± 0,74; TM: 8,10 ± 1,31) e duração do fluxo reverso em veias pulmonares [Saudável: 74,0 (59,0-74,0); Anemia: 70,5 (67,0-74,0); TM: 111 (87,0-120) ms]. Arazão E/A mitral foi maior no grupo TM do que no grupo Anemia (Saudável: 1,80 ± 0,40; Anemia: 1,80 ± 0,24; TM: 2,03 ± 0,34). Não foram encontradas diferenças entre os grupos em variáveis estruturais do ventrículo esquerdo e em índices de função sistólica. CONCLUSÃO: A ecocardiografia com Doppler convencional e o Doppler tecidual permite que alterações na função diastólica do ventrículo esquerdo sejam identificadas em pacientes assintomáticos com talassemia major.

BACKGROUND: Patients with thalassemia major present chronic hemolysis and require regular blood transfusions which may cause iron overload cardiomyopathy and chronic heart failure. Hemochromatosis is characterized by excessive iron accumulation in tissues, and heart involvement is the main cause of death in patients with thalassemia. OBJECTIVE: The aim of this study was to evaluate cardiac structure and function by conventional Doppler echocardiography and tissue Doppler imaging in patients with TM and no clinical evidence of heart failure. METHODS: This is a prospective observational study including 18 patients with thalassemia major (TM) receiving regular blood transfusion. To separately evaluate anemia and blood transfusion effects, two gender, age, weight, and height-matched control groups were included: one with healthy individuals (Healthy, n=18) and one with iron deficient anemia patients (Anemia, n=18). Statistical analysis was performed using ANOVA followed by Tukey's test or Kruskal-Wallis's and Dunn's test. RESULTS: The following echocardiographic variables presented significantly higher values in TM than the Anemia and Healthy groups: left atrium volume index (Healthy: 16.4±6.08; Anemia: 17.9±7.02; TM: 24.1±8.30 cm³/m²); mitral septal E/Em ratio (Healthy: 6.55±1.60; Anemia: 6.74±0.74; TM: 8.10±1.31); and duration of reverse pulmonary vein flow [Healthy: 74.0 (59.0-74.0); Anemia: 70.5 (67.0-74.0); TM: 111 (87.0-120) ms]. The mitral E/A ratio was higher in TM than Anemia (Healthy: 1.80±0.40; Anemia: 1.80±0.24; TM: 2.03±0.34). No differences were found in left ventricular structures and systolic function indexes. CONCLUSION: Conventional Doppler echocardiography and tissue Doppler allow changes in left ventricular diastolic function to be identified in asymptomatic patients with thalassemia major.

Purpura trombocitopenica apos vacina de hepatite B: relato de caso / Thrombocytopenic purpura after hepatitis B: case report

Descrever um caso de purpura trombocitopenica apos vacinacao de hepatite B recombinante...