Pulmonary Hypertension in Patients with β Thalassemia Intermedia and its Correlation with the β Chain Genotype

Abstract

SUMMARY P atients with β thalassemia intermedia (TI) have a milder anemia compared to patients with β thalassemia major, and usually present to medical attention later in childhood and remain largely transfusion independent. Pulmonary hypertension (PHT) was found to occur at a relatively high frequency compared to patients with thalassemia major with significant long-term morbidity. This study aimed at detecting the frequency of pulmonary hypertension among patients with β-thalassemia intermedia, its risk factors and its association with the associated β-chain genotypes. A cross-sectional study included 34 patients with β-TI was performed in Ain Shams University, Pediatric Hospital, Hematology Unit, in the period from February to December 2015. Included patients underwent revision of hospital records, history taking (forage, age of diagnosis, age of first blood transfusion, number of blood transfusions/ year, history of splenectomy, chelation therapy, hydroxy-urea treatment, hospital admission and history of complication), clinical examination, laboratory investigations, genotyping by chain strip analysis and echocardiography (M-Mode, 2D echo and Doppler echo) after providing a verbal consent. Patients were considered to have pulmonary hypertension when right ventricular systolic pressure (RVSP) > 30 mm Hg. The studied Patients hada mean age of 10.22 ± 4.75years (ranged from 4 to 20 years) a.Twenty four patients (70.6%) were transfusion dependent with a median transfusion index over the last year 94.3 ranging 39.7 – 281.1 ml/kg/year. 13 (38.2%) patients were on HU, 22 patients (64.7%) patients were on iron chelators, 3 patients (8.8%) were splenectomized within maximum period of 2 years. According to our results of molecular testing, 14 patients (41.2%) were compound heterozygotes for a β-globin mutation, 12 patients (35.3%) were homozygotes and 8 patients (23.5%) were heterozygotes. The commonly encountered mutations were IVS 1.6 [T>C] for which 10 patients (29.4%) were homozygotes and 9 patients were heterozygotes (26.47) then IVS 1.110 [G>A] for which 3 patients (8.8%) were homozygotes and 3 patients (8.8%) were heterozygotes with IVS 1.6 [T>C]. These mutations followed by IVS 2.1 [G>A], IVS 2.848 [C>A] and IVS 2.745 [C>G] mutations. The frequency of PHT in this study was 41.2% of which 57.1% were compound heterozygotes, 28.6% homozygotes and 14.3% heterozygotes. There was no statistically significant difference between the studied βTI patients with and without PHT as regard blood transfusion, HU and iron chelators intake. Patients with PHT had significant higher total serum bilirubin 1.55 ± 0.56 mg/dl, higher LDH 515.21 ± 190.86 U/L, serum ferritin 1757.00 µg/L (1082 – 2239), reticulocyte count 3.13 ± 1.05% compared to those with normal pulmonary pressure 1.55 ± 0.56 mg/dl, p= 0.009, 333.55 ± 96.00 U/L, p= 0.001, 576.00 (296 – 1716) µg/L, p= 0.042 and 2.45 ± 0.55%, p= 0.019 respectively. On the other hand, patients with PHT had significant lower levels of the initial RBCs 3.12 ± 0.67, initial HB 6.41 ± 1.43 g/dl and initial HCT 19.86 ± 4.15% compared to those without PHT 3.72 ± 0.55, p= 0.007, 7.64 ± 1.09 g/dl, p= 0.008 and 23.71 ± 3.39, p= 0.006 respectively. There was a positive correlation between the genotype of the patients and LDH (p= 0.046, r= 3.402), mean HB (p= 0.003, r= 16.235) and intial HB (p= 0.020, r= 4.448). Compound heterozygote patients had higher LDH (468.50 ± 173.80) and lower HB (6.48 ± 1.27) compared to other patients. Also, there was statistically significant Correlation between the genotypes of the patients and transfusion dependency, p= 0.001, splenomegaly, p= 0.029 and intake of iron chelators, p=0.027.