Myocardial Iron Loading in Patients With Thalassemia Major in Turkey and the Potential Role of Splenectomy in Myocardial Siderosis

Aydınok, Yeşim; Bayraktaroğlu, Selen; Yıldız, Dilek; Alper, Hüdaver

doi:10.1097/mph.0b013e31820c34ef

Cited by 28 publications

(25 citation statements)

References 16 publications

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“…The intact spleen may be a reservoir of excess iron and may have a possible scavenging effect on iron free fractions including non-transferrinbound iron [40]. A role for splenectomy in increased cardiac siderosis has recently been suggested [41]. Nonetheless, splenectomy was also associated with higher rates of endocrinopathy in patients with low serum ferritin levels, suggesting that other contributing factors may be involved.…”

Section: Discussionmentioning

confidence: 97%

Serum ferritin levels and endocrinopathy in medically treated patients with β thalassemia major

et al. 2012

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The association between iron overload indices and pathology of the heart and liver in transfusion-dependent patients with β thalassemia major (TM) has been extensively studied. Nonetheless, data on endocrine disease remains limited. This was a cross-sectional study of 382 TM patients treated with regular transfusions and desferrioxamine at the Thalassemia Center in Dubai, UAE. Retrieved data included demographics, splenectomy status, steady-state serum ferritin levels, and the presence of endocrinopathies (diabetes mellitus, hypothyroidism, hypoparathyroidism, and hypogonadism). Multivariate logistic regression analyses were used to determine which variables were independently associated with the occurrence of each endocrinopathy. The mean age of patients was 15.4 ± 7.6 years, with an equal sex distribution. The mean serum ferritin level was 2597.2 ± 1976.8 μg/l. The frequencies of specific endocrinopathies were diabetes mellitus (10.5%), hypothyroidism (6.3%), hypoparathyroidism (10.5%), and hypogonadism (25.9%). On multivariate logistic regression analysis, patients with a serum ferritin level >2,500 μg/l, but not >1,000-2,500 μg/l, were 3.53 times (95% CI 1.09-11.40) more likely to have diabetes mellitus, 3.25 times (95% CI 1.07-10.90) more likely to have hypothyroidism, 3.27 times (95% CI 1.27-8.39) more likely to have hypoparathyroidism, and 2.75 times (95% CI 1.38-5.49) more likely to have hypogonadism compared to patients with a serum ferritin level ≤1,000 μg/l. However, splenectomized patients with serum ferritin levels ≤2,500 μg/l had comparably high rates of all endocrinopathies as patients with serum ferritin levels >2,500 μg/l. Endocrinopathy is common in TM patients treated with desferrioxamine therapy, especially in patients with serum ferritin levels >2,500 μg/l or those splenectomized.

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Section: Discussionmentioning

confidence: 97%

Serum ferritin levels and endocrinopathy in medically treated patients with β thalassemia major

et al. 2012

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“…The distribution of iron in the body is altered by splenectomy, likely from a decrease in the iron storage capacity in the macrophage compartment (32). NTBI and extrahepatic iron were reported to be higher in splenectomized subjects with iron overload (33–35), which would increase the exposure of blood and BM cells to toxic iron species. Thus, mtDNA damage may be a surrogate marker for NTBI.…”

Section: Discussionmentioning

confidence: 99%

Increased mitochondrial DNA deletions and copy number in transfusion-dependent thalassemia

Lal¹,

Gómez²,

Calloway³

2016

JCI Insight

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BACKGROUND Iron overload is the primary cause of morbidity in transfusion-dependent thalassemia. Increase in iron causes mitochondrial dysfunction under experimental conditions, but the occurrence and significance of mitochondrial damage is not understood in patients with thalassemia. METHODS Mitochondrial DNA (mtDNA) to nuclear DNA copy number (Mt/N) and frequency of the common 4977-bp mitochondrial deletion (ΔmtDNA4977) were quantified using a quantitative PCR assay on whole blood samples from 38 subjects with thalassemia who were receiving regular transfusions. RESULTS Compared with healthy controls, Mt/N and ΔmtDNA4977 frequency were elevated in thalassemia (P = 0.038 and P < 0.001, respectively). ΔmtDNA4977 was increased in the presence of either liver iron concentration > 15 mg/g dry-weight or splenectomy, with the highest levels observed in subjects who had both risk factors (P = 0.003). Myocardial iron (MRI T2* < 20 ms) was present in 0%, 22%, and 46% of subjects with ΔmtDNA4977 frequency < 20, 20–40, and > 40/1 × 107 mtDNA, respectively (P = 0.025). Subjects with Mt/N values below the group median had significantly lower Matsuda insulin sensitivity index (5.76 ± 0.53) compared with the high Mt/N group (9.11 ± 0.95, P = 0.008). CONCLUSION Individuals with transfusion-dependent thalassemia demonstrate age-related increase in mtDNA damage in leukocytes. These changes are markedly amplified by splenectomy and are associated with extrahepatic iron deposition. Elevated mtDNA damage in blood cells may predict the risk of iron-associated organ damage in thalassemia.

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“…It was associated with more blood transfusions, possibly augmented by increased ineffective erythropoiesis [33], and a possible role of the spleen in the iron regulation [40]. Besides being toxic to the heart, liver and endocrine organs, chronic iron overload causes inflammation and oxidative stress to EC [41,42,43], RBCs, platelets and neutrophils [30], which could lead to more hemolysis and hypercoagulability [30].…”

Section: Discussionmentioning

confidence: 99%

Intravascular Hemolysis, Vascular Endothelial Cell Activation and Thrombophilia in Splenectomized Patients with Hemoglobin E/β-Thalassemia Disease

Atichartakarn

Chuncharunee²,

Archararit³

et al. 2014

Acta Haematol

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The relationship between asplenia and thrombophilia in β-thalassemia disease patients is not yet completely understood. One hundred and ten adult hemoglobin (Hb) E/β-thalassemia (E/β-Thal) disease outpatients, dichotomized according to the presence or absence of the spleen, were prospectively studied for evidence of intravascular hemolysis (IVH) and vascular endothelial cell (EC) activation. Biomarkers of IVH (serum cell-free Hb), EC [soluble E-selectin (sE-selectin) and soluble vascular cell adhesion molecule 1 (sVCAM-1)], platelet and EC [soluble P-selectin (sP-selectin)], inflammation [high-sensitivity C-reactive protein (hs-CRP)], and coagulation [thrombin-antithrombin complexes (TAT)] activation, as well as other selected blood tests were determined. The 61 splenectomized patients had a more severe hemolytic disease and higher levels of cell-free Hb and ferritin (p = 0.003), sE-selectin, sP-selectin, hs-CRP, and TAT (p < 0.05). However, serum levels of sVCAM-1 were not different between the two groups. The findings suggested IVH and EC activation. Together with chronic iron overload and chronic low-grade inflammation activation, the findings extend our understanding of the mechanism of thrombophilia in splenectomized E/β-Thal disease patients.

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Myocardial Iron Loading in Patients With Thalassemia Major in Turkey and the Potential Role of Splenectomy in Myocardial Siderosis

Cited by 28 publications

References 16 publications

Serum ferritin levels and endocrinopathy in medically treated patients with β thalassemia major

Serum ferritin levels and endocrinopathy in medically treated patients with β thalassemia major

Increased mitochondrial DNA deletions and copy number in transfusion-dependent thalassemia

Intravascular Hemolysis, Vascular Endothelial Cell Activation and Thrombophilia in Splenectomized Patients with Hemoglobin E/β-Thalassemia Disease

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