title: Elevated liver iron concentration is a marker of increased morbidity in patients with β thalassemia intermedia.
abstract: BACKGROUND
  Patients 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.
  
  
  METHODS
  This 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  Elevated liver iron concentration in patients with β thalassemia intermedia is a marker of increased vascular, endocrine, and bone disease.
authors.affiliation: Department of Internal Medicine, Division of Hematology & Oncology, American University of Beirut Medical Center, Beirut, Lebanon.
authors.forename: Khaled M
authors.initials: KM
authors.lastname: Musallam
authors.forename: Maria Domenica
authors.initials: MD
authors.lastname: Cappellini
authors.forename: John C
authors.initials: JC
authors.lastname: Wood
authors.forename: Irene
authors.initials: I
authors.lastname: Motta
authors.forename: Giovanna
authors.initials: G
authors.lastname: Graziadei
authors.forename: Hani
authors.initials: H
authors.lastname: Tamim
authors.forename: Ali T
authors.initials: AT
authors.lastname: Taher
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism / Q000473:pathology; D001803:Blood Transfusion; D003430:Cross-Sectional Studies; D004906:Erythrocyte Count; D004913:Erythrocytes, Abnormal / Q000378:metabolism / Q000473:pathology; D005260:Female; D005293:Ferritins / Q000097:blood; D005319:Fetal Hemoglobin / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism*; D019190:Iron Overload / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D013156:Splenectomy; D017086:beta-Thalassemia / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology
chemical_list: D015415:Biomarkers; D005293:Ferritins; D005319:Fetal Hemoglobin; D007501:Iron