Chronic Hemolysis May Adversely Affect Skeletal Health. A Cross-Sectional Study of a Pediatric Population.

Hereditary hemolytic disorders cause ineffective erythropoiesis and bone marrow hyperplasia. Little is known about their effect on growth and skeletal health. The aim of this study was to evaluate growth, bone and body composition of non transfusion-dependent (NTD) pediatric patients with chronic hemolysis. A detailed history and clinical examination, dual-energy X-ray absorptiometry (DXA) of the lumbar spine (LS) and total body less head (TBLH) and bone turnover markers were performed. Thirty-nine patients (22 males and 17 females, 20 prepubertal), aged 11.4 ± 3.6 years [14 had ß-thalassemia intermedia (ß-TI), 17 α-thalassemia (α-thal) and eight hereditary spherocytosis (HS)] were evaluated. Fifty-seven previously studied controls were used for statistical analysis. The patients had lower weight and body mass index (BMI) (Z-scores -0.2 and -0.3, respectively, p < 0.05). Post-traumatic fractures were reported by 28.0% of the patients. Compared to controls, they had lower lumbar and subcranial bone mineral density (BMD), as well as reduced fat mass (FM), whereas muscle mass was not affected. One in three patients had low vitamin D and there was increased bone resorption and reduced bone formation. Correlations between different parameters revealed a potential role of osteocalcin, hemoglobin (Hb) and lactate dehydrogenase (LDH) as prognostic markers for bone health, in the setting of chronic hemolysis. Hereditary spherocytosis (HS) patients were the least affected in terms of growth and bone profile. Chronic hemolysis may lead to impaired growth and bone health, even in young, NTD patients. The degree of hemolysis determines bone health risk. Regular surveillance of bone health is justifiable.

Bone health evaluation of children and adolescents with homozygous ß-thalassemia: implications for practice.

OBJECTIVE: Bone tissue is adversely affected in patients with homozygous ß-thalassemia. The aim of this study was to find warning signs of bone loss in young patients with ß-thalassemia and allow prompt therapeutic interventions. METHODS: Thirty-eight patients were studied, 20 boys and 18 girls, aged 5 to 18 years (median = 14.13 y), on regular transfusions and chelation treatments. Their bone mineral density (BMD) was measured with dual x-ray absorptiometry. The recorded parameters were weight, height, bone age (BA), transfusion adequacy (mean fetal hemoglobin value), and chelation efficacy (mean ferritin value, compliance). Tanner stage was also evaluated: 8 prepubertal subjects (stage 1), 18 peripubertal subjects (stages 2 and 3), and 12 postpubertal patients (stages 4 and 5). Blood and urine samples were collected for biochemical analysis. RESULTS: Mean BMD z score was -1.56 ± 1.25. Thirteen patients had normal BMD (z score >-1), 17 patients had low BMD (z score: -1 up to -2.4), and 8 patients had very low BMD (z score <-2.5). Low BMD was observed in patients older than 12 years and was associated with short stature (r = 0.33, P = 0.04), delayed BA (r = 0.61, P = 0.01), and increased bone formation markers. There was no correlation of BMD z score with sex, fetal hemoglobin value, ferritin, and compliance. Regarding Tanner stage, it was associated strongly with short stature (r = 0.57, P = 0.01), ferritin (r = -0.38, P = 0.02), and compliance (r = 0.58, P = 0.01). CONCLUSIONS: [corrected] The decline in BMD may start early, even in the well-transfused patients. This study targets the young patients who are mostly at the risk for bone loss, that is short adolescents with delayed BA. Their prompt recognition in everyday practice is important, as they will need close monitoring of their BMD and metabolic bone profile. In addition, therapeutic interventions, such as adequate calcium intake and sunlight exposure, weight-bearing exercise and, in cases of vitamin D insufficiency, proper supplementation could be suggested.

Impact of magnetic resonance imaging on cardiac mortality in thalassemia major.

PURPOSE: To evaluate whether the introduction of magnetic resonance imaging (MRI) in the management of thalassemia major (TM) patients has affected the risk of cardiac death. MATERIALS AND METHODS: In all, 804 TM patients from two large reference units were included and the risk of dying of cardiac causes, before and after their first MRI, was assessed by a Cox proportional hazards model with time-dependent covariates. RESULTS: Adding information from MRI reduced the risk of cardiac death from 6.0 deaths/1000 patient-years to 3.9 deaths/1000 patient-years (P = 0.22). The risk of cardiac death before having an MRI study was 82% higher compared to the risk observed after the first MRI. CONCLUSION: MRI has become a vital component of ongoing management and seems to have a beneficial effect on cardiac mortality in TM.

Survival in a large cohort of Greek patients with transfusion-dependent beta thalassaemia and mortality ratios compared to the general population.

BACKGROUND: With transfusions and chelation therapy, the prognosis for transfusion-dependent beta thalassaemia has changed from being fatal in early childhood to a chronic disorder with prolonged survival. DESIGN AND METHODS: In this historical prospective study, we present survival, causes of death and mortality ratios compared to the general population in 1044 Greek patients with transfusion-dependent beta thalassaemia. RESULTS: At the age of 50years, the overall survival was 65.0%, while the cardiac death-free survival was 77%. Birth cohort had a significant effect on survival (P<0.001) with a negative trend towards past decades. The standardised mortality ratio (standardised for sex and ages 20-40years) compared to the general population improved significantly from 28.9 in 1990-1999 to 13.5 in 2000-2008, while the standardised cardiac mortality ratio reduced from 322.9 to 106.6, respectively. CONCLUSIONS: Survival in thalassaemia has dramatically improved over the last twenty years but mortality remains significantly increased, compared to the general population.

Correlation of echocardiography parameters with cardiac magnetic resonance imaging in transfusion-dependent thalassaemia major.

BACKGROUND AND OBJECTIVE: Heart iron load (cardiac Fe) can be indirectly quantified by cardiac magnetic resonance (CMR) T2*. CMR accessibility is limited, whereas echocardiography (Echo) is relatively inexpensive and readily available. The objective was to find Echo parameters that may be useful for predicting cardiac Fe. DESIGN AND METHODS: We compared a number of parameters derived from Echo to cardiac Fe in 142 thalassaemia major patients who had undergone a CMR study. RESULTS: All patients with decreased left ventricular (LV) function had cardiac Fe. After removing those patients from the analysis, the total diameter index (Tdi) >5.57 cms/m2, left atrial diameter index >2.41 cm/m2, and the diastolic parameter E/A > 1.96 were highly specific (91.4%, 97.1% and 96.9% respectively) but had low sensitivity (31.8%, 20.45% and 21.8%) in predicting iron load. A right ventricular index >1.47 cm/m2, LV systolic index >2.26 cm/m2 or Tdi >6.26 cm/m2 discriminated between patients with no, or mild to moderate cardiac Fe from those with heavy load, with specificity of 91%, 98.5%, and 98.5%, respectively, but with low sensitivity. INTERPRETATION AND CONCLUSIONS: Echo parameters for cardiac Fe prediction have restricted value, whereas CMR is essential to assess cardiac Fe. However, patients with decreased LV systolic function should be considered a priori as having cardiac Fe, and chelation therapy should be intensified. This also applies to patients who have the above-described Echo criterion values, even if CMR is not available. Once a patient is found by CMR to have cardiac Fe, then the above Echo criterion values may be useful for ongoing monitoring.

Cardiac status in well-treated patients with thalassemia major.

OBJECTIVE: To assess cardiac status in a large group of patients with thalassemia major who had been treated in a standard way since their early infancy with intensive transfusions and deferoxamine chelation therapy and who had good compliance with this regimen. METHODS AND RESULTS: We assessed clinically and echocardiographically 202 thalassemia major patients aged 27.3 +/- 6.3 yr and 75 age and sex-matched healthy controls. Overt cardiac disease was encountered in 14 patients (6.9%), including 5 (2.5%) with congestive heart failure, aged 26-37 yr, and 9 with systolic left ventricular (LV) dysfunction, aged 23-37 yr. Ten patients (5.0%) had a history of pericarditis. Left atrial and LV diameters, LV mass and cardiac output were significantly higher in patients than in controls, while peripheral resistance and LV afterload were significantly lower. Relative LV wall thickness did not differ between patients and controls, but it was significantly lower in patients with overt cardiac disease compared to those without (P < 0.05). Restrictive LV filling was observed in 37.6% of patients and was significantly more frequent in cases with overt cardiac disease (P < 0.01). Pulmonary hypertension was practically absent. Hematological parameters and pulmonary artery pressure levels were not independently associated with the presence of overt cardiac disease. CONCLUSION: Strict lifelong adherence to the standard transfusion and deferoxamine therapy reduces considerably the occurrence of heart failure, LV dysfunction and pericarditis, prevents early heart failure and pulmonary hypertension, but does not eliminate completely cardiac disease in patients with thalassemia major.