T2* MRI in Regularly Transfused Children with Thalassemia Intermedia: Serum Ferritin Does Not Reflect Liver Iron Stores

Nontransfused patients with thalassemia intermedia (TI) accumulate iron due to increased gastrointestinal absorption of iron. Recent studies using T2* MRI revealed that serum ferritin does not reflect the severity of iron overload in nontransfused TI patients. We evaluated the iron overload status in TI children on monthly transfusion. Based on serum ferritin levels, 11 such patients (mean age 13.18 ± 4.09 years), were classified into two groups, group 1 (six patients) and group 2 (five patients) with serum ferritin levels below and above 1000 ng/mL, respectively. T2* MRI assessments were done for evaluation of hepatic and cardiac iron status. Group 1 and group 2 had mean serum ferritin levels of 817.300 ± 244.690 ng/mL and 1983.80 ± 662.862 ng/mL, respectively (P = .003). T2* MRI showed comparable moderate to severe hepatic iron overload status in both. None of the patients had myocardial iron deposition. We conclude that serum ferritin does not reflect the hepatic iron overload status in our patients with TI on regular transfusion.     

Coagulation Contact Phase Factors and Inhibitors in β-Thalassemia Major Children

Selected hemostatic parameters of 23 children affected by β-thalassemia major were studied and compared to an age- and sex-matched group. Plasma prekallikrein level was reduced in all patients, splenectomized or not. In splenectomized patients, platelet count and in vitro platelet aggregability were significantly increased and Protein C was slightly increased. The activated partial thromboplastin time was prolonged and the normotest reduced. Finally, a reduction in the plasma levels of fibrinogen and of vitamin K-dependent proteins, including the antithrom-botic Protein C, was observed in nonsplenectomized patients. Our data indicate that the hemostatic system in patients with thalassemia major may be altered. The relationship between these laboratory changes and clinical manifestations remains to be established.     

Serum ferritin underestimates liver iron concentration in transfusion independent thalassemia patients as compared to regularly transfused thalassemia and sickle cell patients

Serum ferritin (SF) and liver iron concentration (LIC), as measured by SQUID biosusceptometry, were assessed in a convenience sample of transfusion independent thalassemia patients (nTx-Thal, n=26), regularly transfused thalassemia (Tx-Thal, n=89), or sickle cell patients (SCD, n=45) to investigate the severity of iron overload and the relationship between SF and LIC in nTx-Thal compared to SCD and Tx-Thal. SF correlated with LIC (RS=0.53, P<0.001), but was found to be a poor predictor for LIC. SF was significantly lower (P<0.001) in nTx-Thal patients than in other groups, despite similar LIC values. The SF-to-LIC ratio was significantly lower in nTx-Thal compared to Tx-Thal and SCD patients (median of 0.32, 0.87, and 1.2, respectively: P<0.001). Due to underestimation of LIC by ferritin levels, chelation treatment may be delayed or misdirected in patients with thalassemia intermedia.     

Ringed sideroblasts in β‐thalassemia

Symptomatic β‐thalassemia is one of the globally most common inherited disorders. The initial clinical presentation is variable. Although common hematological analyses are typically sufficient to diagnose the disease, sometimes the diagnosis can be more challenging. We describe a series of patients with β‐thalassemia whose diagnosis was delayed, required bone marrow examination in one affected member of each family, and revealed ringed sideroblasts, highlighting the association of this morphological finding with these disorders. Thus, in the absence of characteristic congenital sideroblastic mutations or causes of acquired sideroblastic anemia, the presence of ringed sideroblasts should raise the suspicion of β‐thalassemia.     

Comparative Assessment of Deferiprone and Deferasirox in Thalassemia Major Patients in the First Two Decades-Single Centre Experience

Iron overload is mainly responsible for the morbidity and mortality in patients with beta thalassemia major (TM). Our aim was to compare treatment outcomes with oral iron chelators, deferiprone (DFP), and deferasirox (DFX) in the first two decades on therapy. Seventy patients with TM (mean age ± SD, 7.9 ± 4.2; range 1.5–17 years) attending the pediatric day care unit for regular transfusional support were enrolled in this cross-sectional cohort study. The patients were treated either with DFP at the dose of 75–100 mg/kg/d in three divided doses after food or DFX at the dose of 25–40 mg/kg/d as single dose before food. Mean serum ferritin (±SD) was lower in patients below 10 years (n = 44) at 1283 (±600) ng/mL when compared with patients ≥10 years (n = 19) at 1546 (±589) ng/mL. There was no significant difference in mean serum ferritin (±SD) level in patients receiving DFP (1360 ± 589) versus DFX (1260 ± 641) in this cohort, P > 0.05. 67% of the patients had Vitamin D deficiency (<50 umol/L). Our results show comparable efficacy of DFP and DFX with regards to iron chelation as estimated by serial serum ferritin levels; however, MRI T2* values were higher in the DFP-treated patients compared to DFX treatment.     

Desferoxamine and Urinary Zinc Excretion in β-Thalassemia Major

This study has been undertaken to find out whether urinary zinc excretion, which is already increased in patients with thalassemia, is further increased by usual and high doses of desferrioxamine (DF). A total of 11 β-thalassemia major patients were included. DF infusions have been performed with doses, either 50 mg/kg or 150 mg/kg. Nine age and sex matched normal children were taken as the control group. The mean basal-Zn excretion of the patients was significantly higher than the mean Zn excretion observed in controls. No significant difference is observed between the mean Zn excretion obtained on different doses of DF. However, they are both significantly higher than the mean basal-Zn levels of the controls.     

Neurocognitive function in patients with β‐thalassemia major

Background: Children with β‐thalassemia major (β‐TM) have multiple risk factors for developing cognitive impairment. The aim of the present study was to evaluate cognitive function in patients with β‐TM. Methods: Twenty children with β‐TM were enrolled into the study and were compared with a control group consisting of 21 healthy children. All participants were evaluated with neuropsychological tests and event‐related potentials (ERP). Results: All of the participants had normal IQ scores, but the patient group had significantly lower full‐scale, performance, and verbal IQs compared with the control group (P < 0.05). The number of children with visuomotor dysfunction was higher in the patient group compared with the control group (P < 0.05). In the P300 test, the patient group had significantly prolonged N1, P2 and N2 latencies at the FZ, and a prolonged N1 latency at the Cz compared with the control group (P < 0.05). The patient group also had lower N1 and P3N4 amplitudes at the Fz, and lower N1, N1P2 and P3N4 amplitudes at the Cz when compared with the control group (P < 0.05). Mismatch negativity latency and duration were longer in the patient group (P < 0.05). Conclusions: Neuropsychological tests are safe, and reliable for the diagnosis of cognitive impairment in β‐TM patients, and the use of ERP may facilitate early diagnosis. The number of β‐TM patients in the present study was limited, however, and larger numbers of patients are required in further studies.     

Liver transplantation from a deceased donor with β‐thalassemia intermedia is not contraindicated: A case report

The use of extended criteria donors who might have previously been deemed unsuitable is an option to increase the organ supply for transplantation. This report presents a pediatric case of a successful liver transplantation from a donor with β‐thalassemia intermedia. A patient, 6‐year‐old female, with a diagnosis of cryptogenic liver cirrhosis underwent deceased donor liver transplantation from a thalassemic donor. Extreme hyperferritinemia was detected shortly after transplantation. The most probable cause of hyperferritinemia was iron overload secondary to transplantation of a hemosiderotic liver. Hepatocellular injury due to acute graft rejection might have contributed to elevated ferritin levels by causing release of stored iron from the hemosiderotic liver graft. Iron chelation and phlebotomy therapies were started simultaneously in the early postoperative period to avoid iron‐related organ toxicity and transplant failure. Follow‐up with monthly phlebotomies after discharge yielded a favorable outcome with normal transplant functions. Thalassemia intermedia patients can be candidates of liver donors to decrease pretransplant waitlist mortality. After transplantation of a hemosiderotic liver, it is important to monitor the recipient in terms of iron overload and toxicity. Early attempts to lower iron burden including chelation therapy and/or phlebotomy should be considered to avoid organ toxicity and transplant failure.     

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??To study the status of myocardial T2* and liver T2* in β- thalassemia major??β-TM?? patients with iron overload and its relationship with clinical test data. Methods??In June 2010??on a voluntary basis??out of the 80 β-TM patients over 7 years under regular blood transfusion therapy??51 were chosen to receive myocardial MRI T2* ??myocardial T2*?? and liver MRI T2* ??liver T2*?? tests. The results were compared with age??SF??LVEF??transfusion time??chelation time and Hb. Results??Eleven out of 51 cases ??21.6%?? were myocardial iron overload??including 3 mild cases??3 moderate cases and 5 severe cases. Forty-three out of 51 cases ??84.3%?? were liver iron overload??including 14 mild cases??17 moderate cases and 12 severe cases. There was no correlation between myocardial T2* and SF??LVEF or liver T2*. SF was positively correlated with liver T2*??r = 0.558??P < 0.01??. The transfusion time of myocardial T2* > 20 ms group was less than that of myocardial T2* < 20 ms group ??P < 0.05??. There was no statistical significance between the liver iron overload incidence ratios of the two groups ??P > 0.05?? . Two out of 11 myocardial iron overload cases had lower LVEF??18.2%??. Conclusion??The group of TM patients demonstrates lower myocardial iron overload incidence and higher liver iron overload incidence. As SF increases??liver iron overload becomes more severe??myocardial iron overload can not be predicted or determined by examining SF level. There is no correlation between myocardial iron overload and liver iron overload. LVEF can not be a reliable factor to predict myocardial iron overload.     

Prevalence of low bone mass among adolescents with nontransfusion‐dependent hemoglobin E/β‐thalassemia and its relationship with anemia severity

1 Background

Low bone mass is common among adolescents with transfusion‐dependent β‐thalassemia despite adequate transfusion and iron chelation. However, there are few reports regarding bone mineral density (BMD) among adolescents with nontransfusion‐dependent thalassemia (NTDT). Indeed, only BMD data in patients with nontransfusion‐dependent (NTD) β‐thalassemia intermedia have been reported. No previous study has investigated BMD among adolescents with NTD hemoglobin (Hb) E/β‐thalassemia.

2 Objective

To determine the prevalence of low bone mass among adolescents with NTD Hb E/β‐thalassemia and factors relating to low bone mass.

3 Methods

We investigated BMD of lumbar spine (L2–L4; BMDLS) and total body (BMDTB), as measured by dual‐energy X‐ray absorptiometry, in 22 adolescents (aged 13.2–20 years) with NTD Hb E/β‐thalassemia.

4 Results

Low bone mass was found to be 18.2% and 22.7% at the lumbar spine (BMDLS Z‐score adjusted for bone age and height age) and 13.6% and 9.1% at the total body (BMDTB Z‐score adjusted for bone age and height age). Patients with mean Hb level <8 g/dl were more likely to have low bone mass (BMDLS and BMDTB Z‐scores adjusted for bone age) compared to those with Hb level ≥ 8 g/dl. Mean Hb level correlated with BMDLS and BMDTB Z‐scores adjusted for bone age.

5 Conclusion

We demonstrated that a low Hb level was associated with low bone mass among adolescents with NTD Hb E/β‐thalassemia. A significant proportion of low bone mass among these patients highlights the importance of appropriate management, including red cell transfusion, vitamin D and calcium supplementation for improved long‐term bone health.     

Successful unrelated umbilical cord blood transplantation for class 3 β‐thalassemia major using a reduced‐toxicity regimen

Unrelated umbilical CB transplant for class 3 β‐thalassemia major is associated with an increased risk of mortality and non‐engraftment. We describe two patients who underwent successful unrelated umbilical CB transplant using a novel reduced‐toxicity preparative regimen. This regimen may be sufficiently immunosuppressive and myeloablative to ensure engraftment with reduced risks of toxicity and mortality. Close monitoring of HHV‐6 viral load is advised for patients undergoing transplant with this regimen.     

β-Thalassemia with the IVS-l-1 (G → T) mutation in a Japanese girl

We analyzed the hemoglobins of a Japanese girl with β-thalassemia and those of her immediate family. DNA sequencing of the cloned β-globin gene from this patient revealed a point mutation at the IVS-I position 1 (G → T). This rare point mutation has been found in Asian Indians, but this is the first reported Japanese case.