Clinical-Pathological Features of Non-Transfusion Dependent Thalassemia in Adults — a Single Center Study in Hong Kong

Abstract

Introduction: Non-transfusion dependent thalassemia (NTDT) includes HbH disease, β-thalassemia intermedia (β-TI) and HbE/β-thalassemia. The transfusion requirements of patients with NTDT are variable and they are all at risk of developing iron overload and other complications. The prevalent genetic changes in thalassemia are different across geographical territories, accounting largely for the diverse clinical outcomes. The complication profile of NTDT in Southern China is less well studied than other areas. Data on age-related complications is sparse. The present study aims to describe the clinical-pathological features of adult NTDT patients in Hong Kong, and to evaluate the risk factors associated with complications.Method: A single-center observational study was performed during Jan 2017 to Jun 2018. Data collection included review of medical records for demographics; globin genotypes; hepatitis B and C status; transfusion requirement; splenectomy; iron chelation therapy; complications including gallstone disease, hypothyroidism or hypogonadism, diabetes mellitus (DM), extramedullary hematopoiesis (EMH), leg ulcer, venous thrombosis and cerebral ischemia. During the study period, steady state hemoglobin (Hb) and serum ferritin levels in the recent year were obtained; organ iron deposition assessed using liver and cardiac T2* at 1.5T MRI; liver stiffness measured by Fibroscan; and presence of pulmonary arterial hypertension (PAH) evaluated by echocardiography. The disease profile and prevalence of complications were described with descriptive statistics. Factors impacting clinical parameters and development of complication were studied with univariate regressions. Age and sex adjusted β-coefficients or odd ratios were then determined with multivariable regression analysis.Results: A total of 96 Chinese patients were recruited (mean age 50±15 years; 31% patients >60 years; females 66%). There were 63 (65%) patients having deletional HbH disease, 20 (21%) with non-deletional HbH disease (ND-HbHD), and 13 (14%) with β-TI. The mean Hb was 8.9±1.1 g/dL. Transfusion requirement was never in 39 (41%), occasional in 50 (52%), and regular in 7 (7%) patients. Ten (10%) patients were splenectomized. Iron chelation was given to 21 (21%) patients and the median duration of therapy was 3 (range 1-21) years. Respectively 4 (4%) and 2 (2%) patients were hepatitis B and C carriers. The median serum ferritin was 473 [IQR 217-1029] ng/mL. The median liver iron concentration (LIC) estimated by MRI T2* was 3.6 [IQR 1.7-7.1] mg Fe/g with 26% of patients having moderate to severe liver iron overload (≥7.1 Fe mg/g). In the study population, the prevalence of liver fibrosis (liver stiffness ≥7.1kPa) was 26%, gallstones 50%, hypo-thyroidism/-gonadism 8%, DM 16%, EMH 5%, leg ulcer 1%, thrombotic events 2%, cardiac iron overload 1%. No patients had PAH (Table 1).In multivariable regression, advanced age (>60 years) was associated with lower Hb (p=0.03), higher risk of liver fibrosis (p=0.04) and DM (p<0.01). β-TI was associated with higher transfusion requirement (p<0.01), higher serum ferritin (p<0.01) and higher risk of hypo-thyroidism/-gonadism(p=0.01). Both ND-HbHD and β-TI were associated with higher LIC (p<0.01). Patients requiring regular transfusions had higher serum ferritin (p<0.01) and LIC (p<0.01). Occasionally transfused (p=0.01) and female patients (p=0.01) had higher risk of developing gallstones. Splenectomy was associated with higher serum ferritin level (p=0.03). Patients with moderate to severe liver iron overload had increased risk of liver fibrosis (p=0.01) (Table 2).Conclusions: The present study including 1/3 of elderly patients illustrates the heterogeneous clinical features of NTDT in Hong Kong in terms of transfusion requirement and body iron store. HbH disease is the most frequent type of NTDT. Liver iron overload, liver fibrosis, gallstones and DM were the most common complications. Advancing age, β-TI, ND-HbHD were associated with higher risk of developing complications. A low prevalence of EMH, cardiac iron overload, PAH, thrombosis and leg ulcer was observed. Larger prospective study is needed to confirm the prevalence of complications in NTDT in Chinese, which may be different from other ethnic groups, and at the same time to provide more insight to the pathophysiology of NTDT and facilitate establishment of future local management strategies. DisclosuresNo relevant conflicts of interest to declare.