Elevated liver iron concentration is a marker of increased morbidity in patients with   thalassemia intermedia

Abstract

The online version of this article has a Supplementary Appendix. BackgroundPatients with β thalassemia intermedia can have substantial iron overload, irrespectively of their transfusion status, secondary to increased intestinal iron absorption. This study evaluates whether iron overload in patients with β thalassemia intermedia is associated with morbidity. Design and MethodsThis was a cross-sectional study of 168 patients with β thalassemia intermedia treated at two centers in Lebanon and Italy. Data on demographics, splenectomy status, transfusion status, and presence of co-morbidities were retrieved. Laboratory values of serum ferritin, fetal and total hemoglobin levels, as well as platelet and nucleated red blood cell counts were also obtained. Iron burden was determined directly by measuring liver iron concentration using magnetic resonance imaging. Patients were subdivided according to transfusion and splenectomy status into groups with phenotypes of different severity. ResultsThe mean age of the patients was 35.2±12.6 years and 42.9% of them were male. The mean liver iron concentration was 8.4±6.7 mg Fe/g dry weight. On multivariate logistic regression analysis, after adjusting for age, gender, splenectomy status, transfusion status, and laboratory indices, an increase in 1 mg Fe/g dry weight liver iron concentration was independently and significantly associated with higher odds of thrombosis, pulmonary hypertension, hypothyroidism, osteoporosis, and hypogonadism. A liver iron concentration of at least 7 and at least 6 mg Fe/g dry weight were the best thresholds for discriminating the presence and absence of vascular and endocrine/bone morbidities, respectively (area under the receiver-operating characteristic curve: 0.72, P<0.001). Elevated liver iron concentration was associated with an increased rate of morbidity in patients with phenotypes of all severity, with a steeper increase in the rate of vascular morbidity being attributed to aging, and an earlier appearance of endocrine and bone disease. ConclusionsElevated liver iron concentration in patients with β thalassemia intermedia is a marker of increased vascular, endocrine, and bone disease.

Thyroid dysfunction in thalassaemic patients: ferritin as a prognostic marker and combined iron chelators as an ideal therapy

“…It was demonstrated that LIC Ferritin < 1800 (µg/l) Figure 4 Kaplan-Meier survival curves of end-point (thyroid dysfunction incidence during a follow-up period) in patients with serum ferritin levels above and below the optimal receiver operating characteristics cut-off level. was associated with an increased rate of morbidity in patients with bT intermedia, with an increased incidence of vascular morbidity and an earlier appearance of endocrine and bone disease (23). Moreover, the need for iron chelation therapy in these patients who have never been transfused or have received only occasional transfusions has just recently started to emerge after documenting substantially high LIC and non-transferrin-bound iron values in such patients (24,25).…”

Deferiprone versus deferoxamine in thalassemia intermedia: Results from a 5‐year long‐term Italian multicenter randomized clinical trial

“…However, an increased liver iron concentration (LIC) has been shown to be a crucial marker of increased morbidity in TI [2]. Therefore, despite their limited need for transfusions, TI patients may develop clinically relevant iron overload, and guidelines currently recommend initiating iron chelation therapy when either the LIC increases to >7 mg/g dry tissue or the ferritin level is higher than 500 lg/l [3,4].…”

Serum ferritin level and morbidity risk in transfusion-independent patients with -thalassemia intermedia: the ORIENT study

“…Studies that evaluate the risk/benefit of initiating treatment in patients with a less conservative threshold (<800 ng/mL) would also be welcomed. 3 Mehran Karimi, 4 Amal El-Beshlawy, 5 Giovanna Graziadei, 1 Matthew Magestro, 6 Jerome Wulff, 7 Guilhem Pietri, 7 and Ali T. Taher …”

“…2,5,6 This threshold was primarily selected in the light of its established association with morbidity in β-thalassemia intermedia patients, 7,8 as well as recent evidence on the efficacy and safety of iron chelation therapy in non-transfusion-dependent thalassemia (including β-thalassemia intermedia) patients for whom treatment was started at 5 mg Fe/g dw or over (THALASSA trial).…”