Iron overload is a major complication in transfusion-dependent thalassemia (TDT) patients. Chronic oxidative stress from iron overload may lead to cellular damage and viability. This is a cross-sectional study. Transfusion-dependent thalassemia patients aged ⩾18 years old were enrolled. Transfusion-dependent thalassemia patient’s serum and normal volunteer’s serum were separately incubated with healthy peripheral blood mononuclear cells (PBMCs). The cell viability was measured by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay at 24, 48, and 72 hours. Sixty-nine TDT patients and 22 healthy controls were enrolled. The mean of PBMCs viability after incubation with serum from TDT patients was lower than that with the controls (88.65% vs 103.56% at 24 hours, 78.77% vs 112.04%% at 48 hours, and 71.18% vs 132.16%% at 72 hours, respectively). High serum ferritin level (correlation −0.29, P < .05) and white blood cell (WBC) count negatively affected cell viability (correlation −2.86, P = .05). From multivariate analysis, serum ferritin level is the only significant risk factor that is independently associated with cell viability (correlation −11.42, P < .001). Our findings showed that TDT patient’s serum causes decreased cell viability. Serum ferritin level was a significant independent factor influencing cell viability.

BACKGROUND Transfusion dependent thalassemia (TDT) patients is a group of thalassemia patients who require regular blood transfusion. Red blood cell transfusion and increased intestinal iron absorption leads to iron overload. The cellular damage associated with iron overload is mainly mediated by the state of oxidative stress and the effect of free oxygen radicals on various cell components. Telomeres are terminal protein-DNA complexes that stabilize chromosome and prevent DNA from double-stranded breaks. Chronic oxidative stress from iron overload and ineffective erythropoiesis in thalassemia may lead to shortening of telomere length. METHOD We conducted a cross-sectional study in TDT patients aged more than 18 years old who attended the adult hematology clinic at Maharaj Nakorn Chiang Mai hospital, Chiang Mai University, Thailand from 1 January 2016 to 30 April 2016. TDT was defined as thalassemia who requiring a red cell transfusion at least 3 times per year, included both beta-thalassemia and alpha-thalassemia patients. Telomere length was measured by real-time quantitative PCR and compared with matched healthy controls by age and sex. We used Pearson's correlation coefficient to test whether telomere length was associated with any factors. The threshold for statistical significance for all comparisons was chosen as P <0.05. RESULT Thirty TDT patients and 30 matched healthy control were included in this study. For TDT group, there were 19 female patients (63.3%). The median age was 29.2 (18-48) years. Baseline hemoglobin pre-transfusion 6.4 g/dL (5.3-7.4). Of these, there were 18 beta-thalassemia/Hb E disease (60%) who was the majority population. There were 11 beta-thalassemia major patients (36.4%) and 1 HbH with Constant spring patient (3.3%). The median telomeric terminal restriction fragment (TRF) length of TDT thalassemia group was 5.76 (4.94-7.13) kb. The median TRF length of control group was 6.79 (5.52-9.02) kb. TDT patients had significant shorter TRF length compared to control group (age and sex match), (p<0.0001). Telomere shortening in TDT thalassemia is aging-dependent process. The Pearson's coefficient showed the negative correlation between TRF length and age (Pearson's coefficient = 0.176), (p=0.021). There was no correlation of telomere length with other factors such as sex, hemoglobin level, transfusion requirement. CONCLUSION TDT patients had shorter telomere length compared to control group. Telomere shortening in TDT thalassemia is aging-dependent process. Chronic oxidative stress from iron overload and ineffective erythropoiesis in thalassemia may play the significant role in this accelerated telomere shortening process. Table The median telomeric terminal restriction fragment length of TDT patients compared with control group Table. The median telomeric terminal restriction fragment length of TDT patients compared with control group Disclosures No relevant conflicts of interest to declare.