β-Thalassemia Major: Thin-Section CT Features and Correlation with Pulmonary Function and Iron Overload

BACKGROUND: Beta Thalassemia is the most common chronic hemolytic anemia in Egypt (85.1%) with an estimated carrier rate of 9-10.2%. Injury to the liver, whether acute or chronic, eventually results in an increase in serum concentrations of Alanine transaminase (ALT) and Aspartate transaminase (AST).AIM: Evaluating the potentiating effect of iron overload & viral hepatitis infection on the liver enzymes.PATIENTS AND METHODS: Eighty (80) thalassemia major patients were studied with respect to liver enzymes, ferritin, transferrin saturation, HBsAg, anti-HCV antibody and HCV-PCR for anti-HCV positive patients.RESULTS: Fifty % of the patients were anti-HCV positive and 55% of them were HCV-PCR positive. Patients with elevated ALT and AST levels had significantly higher mean serum ferritin than those with normal levels. Anti-HCV positive patients had higher mean serum ferritin, serum ALT, AST and GGT levels and higher age and duration of blood transfusion than the negative group. HCV-PCR positive patients had higher mean serum ferritin and serum ALT and also higher age and duration of blood transfusion than the negative group.CONCLUSION: Iron overload is a main leading cause of elevated liver enzymes, and presence of HCV infection is significantly related to the increased iron overload.

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Evaluation of cardiac and hepatic iron overload in thalassemia major patients with T2* magnetic resonance imaging

Hematology ◽

10.1080/10245332.2017.1292614 ◽

2017 ◽

pp. 1-7 ◽

Cited By ~ 6

Author(s):

Pustika Amalia Wahidiyat ◽

Felix Liauw ◽

Damayanti Sekarsari ◽

Siti Ayu Putriasih ◽

Vasili Berdoukas ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Iron Overload ◽

Thalassemia Major ◽

Hepatic Iron ◽

Resonance Imaging ◽

Hepatic Iron Overload

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Endocrine complications

Thalassemia Reports ◽

10.4081/thal.2018.7479 ◽

2018 ◽

Vol 8 (1) ◽

Author(s):

Vincenzo De Sanctis

Keyword(s):

Iron Overload ◽

Chelation Therapy ◽

Membrane Lipids ◽

Survival Rates ◽

Iron Chelation ◽

Thalassemia Major ◽

Cellular Iron ◽

Active Iron ◽

Bone Changes ◽

Endocrine Complications

More than five decades ago, thalassemia major (TM) was fatal in the first decade of life. This poor prognosis changed since the survival rates started to increase progressively thanks to the implementation of continuous and significant improvement of diagnostic and therapeutic methods, consisting mainly of an intensive transfusion program combined with chelation therapy and imaging methods. Regular red blood cell (RBC) transfusions eliminate the complications of anemia, compensatory bone marrow expansion, bone changes and splenomegaly, restore the physiological growth throughout childhood and extend survival. The most serious disadvantage of life-saving transfusions is the inexorable accumulation of iron within tissues. Iron is physiologically stored intracellularly in the form of ferritin, a protein whose synthesis is induced upon the influx of iron. When the storage capacity of ferritin is exceeded, pathological quantities of metabolically active iron are released intracellularly in the form of hemosiderin and free iron within an expanded labile pool. This metabolically active iron catalyzes the formation of free radicals, which damage membrane lipids and other macromolecules, leading to cell death and eventually organ failure. Other factors contributing to the variability of cellular iron overload are: a) the cell surface transferrin receptors and the capacity of the cells to deploy defence mechanisms against inorganic iron; b) individual susceptibility to iron toxic effect; c) the development of organ(s) damage secondary to persisting severe iron overload in the years preceding iron chelation therapy; and d) liver disorders, chronic hypoxia and associated endocrine complications. Multi-transfused thalassemia major (TM) patients frequently develop severe endocrine complications mainly due to iron overload, anemia, and chronic liver disease, which require prompt diagnosis, treatment and close follow-up by specialists.

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Progressive dysfunction of monocytes associated with iron overload and age in patients with thalassemia major

Blood ◽

10.1182/blood.v67.1.105.bloodjournal671105 ◽

1986 ◽

Vol 67 (1) ◽

pp. 105-109

Author(s):

IJ Ballart ◽

ME Estevez ◽

L Sen ◽

RA Diez ◽

J Giuntoli ◽

...

Keyword(s):

Blood Transfusion ◽

Iron Overload ◽

Liver Damage ◽

Thalassemia Major ◽

Lytic Activity ◽

Blood Monocytes ◽

Peripheral Blood Monocytes ◽

Cell Dysfunction ◽

Positive Effect ◽

Increased Susceptibility

We evaluated phagocytic and lytic activities of peripheral blood monocytes (PBMo) from patients with thalassemia major (ThP) using C pseudotropicalis as the target. PBMo from ThP showed decreased lytic activity (P less than .001), whereas the phagocytic activity did not differ from that of the controls. Significant inverse correlations were found between lytic activity of PBMo and age of patients (r2 = .47; P less than .01) and also between lytic activity and serum ferritin levels (r2 = .65; P less than .001). No association was found between lytic activity and other variables (blood transfusion regimens, therapy with desferrioxamine, liver damage, and the presence of sHBAg). Splenectomy showed no positive effect on PBMo functions from ThP. Our results suggest that PBMo from ThP have an intracellular defect in their microbicidal mechanisms associated with iron overload. This cell dysfunction could be responsible, at least in part, for the increased susceptibility to infections reported in ThP.

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Male Gender Increases the Risk of Liver Fibrosis in Patients with Thalassemia Major Independent of Iron Overload

Blood ◽

10.1182/blood.v128.22.3630.3630 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3630-3630

Author(s):

Murtadha K. Al-Khabori ◽

Said Al Busaifi ◽

Al Ghaliya Al Omairi ◽

Moez Hassan ◽

Humoud Al Dhuhli ◽

...

Keyword(s):

Logistic Regression ◽

Liver Fibrosis ◽

Iron Overload ◽

Iron Concentration ◽

Thalassemia Major ◽

Male Gender ◽

Ultrasound Elastography ◽

P Value ◽

Positive Serology ◽

Multivariable Logistic Regression

Abstract Introduction and Objectives: Iron overload in patients with Thalassemia Major (TM) leads to various complications including liver fibrosis. The independent impact of gender on this risk has been previously investigated but not yet confirmed. We, therefore, planned to assess the independent impact of gender in patients with TM on the risk of liver fibrosis. Methods: We included 96 patients with TM followed and transfused in one academic tertiary hospital. Patients underwent assessment of liver fibrosis using ultrasound elastography (FibroScan device) with a cut off value of 7.8 kPa. The mean ferritin in the 5 years prior to elastography assessment was used to represent iron overload. Association was tested using Chi-squared and the independent impact of gender was confirmed in the multivariable logistic regression with a model that included mean ferritin and gender. Results: The median age of the 96 included patients was 26 years (Interquartile range [IQR]: 22-30). Males constituted 45% of patients and 33% of patients were splenectomised. The median alanine transaminase, aspartate transaminase, albumin and total bilirubin were 30 U/L (IQR: 18-64), 30 U/L (IQR: 18-46), 46 g/L (IQR: 44-48) and 21 µmol/L (IQR: 14-32) respectively. The median ferritin and liver iron concentration assessed by MRI T2* were 1293 µg/L (IQR: 753-2715) and 6.7 mg/gdw (IQR: 3.5-16.1) respectively. Thirty seven percent of patients had positive serology for HCV while 1% of patients had positive serology for HBV. The proportion of patients with fibrosis as assessed by elastography was 59%. The proportion of male patients with fibrosis was 70% compared to 51% in female patients with a trend towards statistical significance (odds ratio [OR] of 2.2 with a p value of 0.094). In the multivariable logistic regression model, both gender (OR of 3.0, P value of 0.0188) and ferritin (OR of 1.0004, p value of 0.0036) were statistically significant independent predictors of liver fibrosis. Conclusion: Male gender increases the risk of liver fibrosis independent from iron overload. Our study confirms the previously suspected but unproven association. Follow up and therapy may be tailored to include gender as a decision factor. Larger studies are needed to further confirm these results. Disclosures No relevant conflicts of interest to declare.

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Association between Native Myocardial T1 Mapping and Cardiac Function and Macroscopic Fibrosis in Thalassemia Major

Blood ◽

10.1182/blood-2020-134585 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 26-27

Author(s):

Alessia Pepe ◽

Nicola Martini ◽

Antonio De Luca ◽

Vincenzo Positano ◽

Laura Pistoia ◽

...

Keyword(s):

Iron Overload ◽

Myocardial Fibrosis ◽

T1 Mapping ◽

Thalassemia Major ◽

Left Ventricular ◽

Lv Function ◽

Myocardial Iron ◽

Native T1 ◽

Molli Sequence ◽

Lv Volume

Background.Cardiovascular magnetic resonance (CMR) is the only available technique for the non-invasive quantification of MIO. The native T1 mapping has recently been proposed as an alternative to the universally adopted T2* technique, due to the higher sensitivity for detection of changes associated with mild or early iron overload. Objective.To study the association between T1 values and left ventricular (LV) function in thalassemia major (TM) and to evaluate for the first time if T1 measurements quantifying MIO are influenced by macroscopic myocardial fibrosis. Methods.146 TM patients (87 females, 38.7±11.1 years) consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network underwent CMR. Native T1 values were obtained by Modified Look-Locker Inversion recovery (MOLLI) sequence in all 16 myocardial segments and the global value was the mean. LV function parameters were quantified by cine images. Late gadolinium enhancement (LGE) technique was used to detect macroscopic myocardial fibrosis. Results.No correlation was detected between global heart T1 values and LV volume indexes, LV mass index, or LV ejection fraction. Foourteen (9.6%) patients had an abnormal LV motion (13 hypokinesia and 1 dyskinesia) and they showed significantly lower global heart T1 values than patients without LV motion abnormalities (883.8±139.7 ms vs 959.0±91.3 ms; P=0.049). LGE images were acquired in 88 patients (60.3%) and macroscopic myocardial fibrosis was detected in 36 patients (40.9%). The 72.2% of patients had two or more foci of fibrosis. Patients with macroscopic myocardial fibrosis had significantly lower global heart T1 values (921.3±100.3 ms vs 974.5±72.7 ms; P=0.027) (Figure 1A). Data about the LGE was present for 1408 segments (88 patients x 16 segments) and 105 (7.5%) were positive. Segments with LGE had significantly lower T1 values than segments LGE-negative (905.6±110.6 ms vs 956.9±103.8 ms; P<0.0001) (Figure 1B). Conclusion.No correlation between T1 values and LV function parameters was detected, probably because the majority of the patients had normal or mild abnormal LV parameters. TM patients with macroscopic myocardial fibrosis showed significantly lower T1 values suggesting that T1 measurements for quantifying MIO are not influenced by macroscopic myocardial fibrosis and an association between myocardial iron and macroscopic fibrosis, previously detected only in pediatric TM patients. Figure Disclosures Pepe: Chiesi Farmaceutici S.p.A.:Other: no profit support and speakers' honoraria;Bayer:Other: no profit support;ApoPharma Inc.:Other: no profit support.Pistoia:Chiesi Farmaceutici S.p.A.:Other: speakers' honoraria.Meloni:Chiesi Farmaceutici S.p.A.:Other: speakers' honoraria.

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