Evaluation of the Clinical and Laboratory Characteristics of Previously Followed-up Thalassemia Intermedia Patients to Provide Them Better Care in the Future O ¨ zlem Tu¨fekc¸i, MD,* Berna Atabay, MD,w Meral Tu¨rker, MD,w S¸ebnem Yılmaz Bengoa, MD,* Salih Go¨zmen, MD,* Tuba Karapınar, MD,* Hale O ¨ ren, MD,* and Gu¨lersu I ˙ rken, MD* Summary: The increased awareness about the severity of compli- cations in thalassemia intermedia patients led authorities to develop strategies for better management and follow-up of these patients. In this study, we aimed to define the clinical and labo- ratory characteristics in previously followed-up b-thalassemia intermedia patients and wanted to gain an insight about the follow- up of this patient population in a developing country to provide them better care in the future. The mean age at diagnosis was 4 years, and the mean hemoglobin was 7.13 g/dL. The mean age at the beginning of regular transfusion was 4.8 years. An overall 74% of patients were on a regular transfusion program. The mean fer- ritin values at diagnosis and the last follow-up were 487 and 1225 ng/mL, respectively. The most common mutations detected in patients were IVS-I-110, IVS-I-6, IVS-II-1, and FCS 8/9 in order of frequency. Complications were seen in 48% of patients. The most common complications were osteopenia/osteoporosis (34%), growth retardation (24%), hypogonadism (18%), and cardiomy- opathy (13%). In conclusion, the relatively higher complication rate in our patients who were previously treated highlights once again the need for an increased effort for optimal management and follow-up of this specific group of patients. Key Words: thalassemia intermedia, transfusion, chelation, morbidity (J Pediatr Hematol Oncol 2017;39:440–444) B eta-thalassemia intermedia (b-TI) indicates a very het- erogenous clinical condition ranging in severity between thalassemia minor, the asymptomatic carrier, and tha- lassemia major, the transfusion-dependent severe form. 1 As its definition is relative, it includes a wide range of clinically and genetically heterogenous patients. The spectrum of b-TI includes, at one end, patients who present between the ages of 2 and 6 years, are able to produce approximately 5 to 6 g/dL of hemoglobin (Hb), show growth retardation, have skeletal abnormalities, and occasionally require transfusions. The spectrum at the other end includes asymptomatic individuals with anemia and splenomegaly diagnosed by chance or during family studies. 2 In between there are cases presenting with varying degrees of clinical severity, which makes the clinical management difficult, as there are no established clinical guidelines. b-TI is also very heterogenous at the genotype level. These patients are most commonly homozygous or com- pound heterozygous for b-thalassemia; less frequently, only a single b-globin locus is mutated. The interaction between various alleles of the b-globin gene with those of a-globin along with other variations like hereditary persistence of fetal Hb are known to be responsible for the varying phe- notype of b-TI. 3 Other factors include tertiary modifiers with polymorphisms affecting bone, iron, and bilirubin metabolisms. 4,5 It is still difficult to consistently predict phenotypes from genotypes. 6 The clinical picture of b-TI patients is dominated by the multiple long-term effects of chronic hemolytic anemia, tis- sue hypoxia, and iron overload. 4,6 Relative folic acid defi- ciency and hypersplenism due to spleen enlargement caused by excessive red cell breakdown or red cell pooling and extramedullary hematopoiesis may worsen anemia. Iron overload is frequently recorded even in untransfused b-TI patients because of ineffective erythropoiesis, peripheral red cell breakdown, and increased intestinal iron absorp- tion. 2,7 Complications are caused by both chronic anemia and iron overload and include growth retardation, skeletal changes, osteopenia/osteoporosis, leg ulcers, cardiac prob- lems, and endocrinological problems. Infectious complica- tions result from both blood-borne infections associated with multiple transfusions and coexistent immune deficiency that constitute a major cause of morbidity and mortality. Alloautoimmunization, hypercoagulability, extramedullary hemopoietic masses, and pseudoxanthoma elasticum are the other complications seen in b-TI. 8–12 The increased awareness about the severity of compli- cations in b-TI patients led authors to develop strategies for better management of these patients. The most difficult therapeutic choice that needs to be made when treating a patient with b-TI is whether or not to initiate a chronic transfusion program. However, the physician must be conscious about the complications that are more commonly observed in non–transfusion-dependent thalassemia patients like those with thrombosis, extramedullary hematopoiesis, and pulmonary hypertension. 13–18 In this study we aimed to define the clinical and lab- oratory characteristics and complications in b-TI patients from a developing country. We also wanted to investigate the impact of age at diagnosis on the severity of skeletal changes and transfusion dependency and tried to answer whether there is an association between growth retardation and the timing and frequency of transfusions in our patients. We believed that the relatively longer follow-up period of our patients would allow us to better define the frequency and diversity of complications and their possible association with some factors. Received for publication August 18, 2016; accepted June 7, 2017. From the *Department of Pediatric Hematology, Dokuz Eylu¨l University Hospital; and wDepartment of Pediatric Hematology- Oncology, Tepecik Research Hospital, I ˙ zmir, Turkey. The authors declare no conflict of interest. Reprints: Hale O ¨ ren, MD, Department of Pediatric Hematology, Dokuz Eylu¨l University Faculty of Medicine, Balcova, I ˙ zmir 35340, Turkey (e-mail: ozlemtufekci@hotmail.com). Copyright r 2017 Wolters Kluwer Health, Inc. All rights reserved. ORIGINAL ARTICLE 440 | www.jpho-online.com J Pediatr Hematol Oncol  Volume 39, Number 6, August 2017 Copyright r 2017 Wolters Kluwer Health, Inc. All rights reserved.