Abstract
Pulmonary hypertension is one of the major complications in patients with thalassemia. The prevalence is higher among patients with non - transfusion dependent thalassemia (NTDT) than those patients with thalassemia major. Patients with NTDT have distinct genetic subgroups. Therefore, the effects of different genotype groups on pulmonary hypertension in patients with NTDT were assessed.
A cross-sectional study was conducted in patients with NTDT aged ≥ 10 years old at Srinagarind University Hospital and Udonthani Hospital. Pulmonary hypertension was defined as a tricuspid regurgitation velocity > 2.9 m/s by trans-thoracic echocardiography. All patients gave consent and the protocol was approved by the Ethics committee of Faculty of Medicine, KhonKaen University and Udonthani Hospital. Clinical characteristics and laboratory data that literature indicated as risk factors for pulmonary hypertension were collected. Genotypes were determined by hemoglobin typing and DNA analysis. The effect of genotype group on pulmonary hypertension was evaluated by using multivariate logistic regression analysis.
Two hundred twenty two patients were recruited, 3 patients were excluded (1 patient with congenital heart disease and 2 patients with valvular heart disease). In a total of 219 patients, pulmonary hypertension was found in 24 patients (10.96%). All patients were categorized into 2 groups according to genetic data that included: 1) β-thalassemia (140, 63.93%) 2) α-thalassemia and combined α and β-thalassemia (79, 36.07%).Genotype groups were statistically and significantly associated with pulmonary hypertension based on the adjusted odds ratios after adjustment for other factors. Patients with β-thalassemia had a statistically significant higher risk for pulmonary hypertension compared to patients with α-thalassemia and patients with combined α and β-thalassemia had an odds ratio of 9.47 (p=0.036).
Genotype group is an independent risk factor for pulmonary hypertension in patients with NTDT. Echocardiography should be routinely recommended in patients with β-thalassemia. In patients with α-thalassemia and combined α and β-thalassemia, pulmonary hypertension is uncommon. Therefore, echocardiography should be only performed when these patients have a clinical indication.
Hb CS = Hemoglobin Constant spring, Hb Pakse´= Hemoglobin Pakse´
PHT= pulmonary hypertension, AOR= adjusted odds ratio, 95% CI= 95% confidence interval
No relevant conflicts of interest to declare.
Clinical characteristic data of 219 patients with thalassemia
| Characteristics . | Patients (n=219) . |
|---|---|
| Age, year (at enrollment) | 27.61 ± 13.66 |
| Sex, (%) | |
| Female | 125 (57.01) |
| Male | 94 (42.99) |
| Age of first diagnosis, year | 9.69± 12.72 |
| Age of first blood transfusion, year | 11.31± 13.75 |
| Splenectomy, (%) | |
| No | 134 (61.20) |
| Yes | 85 (38.80) |
| Duration after splenectomy, year | 12.02± 8.89 |
| Transfusion index (ml/kg/ 6 months) | 25.38± 26.37 |
| Genotype group 1)β-thalassemia | |
| β-thalassemia/Hb E | 139(63.47) |
| Homozygous β-thalassemia | 1(0.46) |
| 2)α-thalassemia and combined α and β-thalassemia | |
| Hb H disease | 11(5.02) |
| Hb H disease with Hb CS | 19(8.68) |
| Hb H disease with HbPakse´ | 5(2.28) |
| EA Bart's disease | 6(2.74) |
| EA Bart's diseae with Hb CS | 30(13.70) |
| EF Bart's disease | 3(1.37) |
| EF Bart's disease with Hb CS | 2(0.91) |
| EA Bart's disease with Hb Pakse´ | 3(1.37) |
| Liver size, cm | 3.47±3.19 |
| Spleen size, cm | 5.90±4.52 |
| Hemoglobin (g/dL) | 7.80±1.19 |
| Platelet ( x 106/L) | 391.71±238.74 |
| Nucleated RBC/100 WBC | 143.10±257.60 |
| Serum ferritin (mg/dL) | 1746.40±1670.97 |
| Echocardiographic findings | |
| Tricuspid regurgitation velocity (m/s) | 2.31±0.45 |
| Left ventricular ejection fraction (%) | 67.63±5.70 |
| Characteristics . | Patients (n=219) . |
|---|---|
| Age, year (at enrollment) | 27.61 ± 13.66 |
| Sex, (%) | |
| Female | 125 (57.01) |
| Male | 94 (42.99) |
| Age of first diagnosis, year | 9.69± 12.72 |
| Age of first blood transfusion, year | 11.31± 13.75 |
| Splenectomy, (%) | |
| No | 134 (61.20) |
| Yes | 85 (38.80) |
| Duration after splenectomy, year | 12.02± 8.89 |
| Transfusion index (ml/kg/ 6 months) | 25.38± 26.37 |
| Genotype group 1)β-thalassemia | |
| β-thalassemia/Hb E | 139(63.47) |
| Homozygous β-thalassemia | 1(0.46) |
| 2)α-thalassemia and combined α and β-thalassemia | |
| Hb H disease | 11(5.02) |
| Hb H disease with Hb CS | 19(8.68) |
| Hb H disease with HbPakse´ | 5(2.28) |
| EA Bart's disease | 6(2.74) |
| EA Bart's diseae with Hb CS | 30(13.70) |
| EF Bart's disease | 3(1.37) |
| EF Bart's disease with Hb CS | 2(0.91) |
| EA Bart's disease with Hb Pakse´ | 3(1.37) |
| Liver size, cm | 3.47±3.19 |
| Spleen size, cm | 5.90±4.52 |
| Hemoglobin (g/dL) | 7.80±1.19 |
| Platelet ( x 106/L) | 391.71±238.74 |
| Nucleated RBC/100 WBC | 143.10±257.60 |
| Serum ferritin (mg/dL) | 1746.40±1670.97 |
| Echocardiographic findings | |
| Tricuspid regurgitation velocity (m/s) | 2.31±0.45 |
| Left ventricular ejection fraction (%) | 67.63±5.70 |
Multivariate analysis of the effect of genotype group on pulmonary hypertension in 219 patients with thalassemia
| Variables . | n . | % of PHT . | AOR . | 95% CI of AOR . | p-value . |
|---|---|---|---|---|---|
| Age (every 10 years) | - | - | 2.02 | 1.00-4.08 | 0.05 |
| Age of first blood transfusion (every 1 year) | - | - | 1.04 | 0.97-1.12 | 0.209 |
| Sex, (%) | |||||
| Female | 125 | 37.50 | 0.14 | 0.03-0.53 | 0.004 |
| Male | 94 | 62.50 | 1 | referent | - |
| Splenectomy, (%) | |||||
| No | 134 | 33.33 | 1 | referent | - |
| Yes | 85 | 66.67 | 306.87 | 14.01-6720.66 | <0.001 |
| Genotype group | |||||
| 1) β-thalassemia | 140 | 87.50 | 9.47 | 1.16-77.34 | 0.036 |
| 2) α-thalassemia and combined α and β-thalassemia | 79 | 12.50 | 1 | referent | - - |
| Nucleated RBC/100 WBC (every 100 nucleated RBC) | - | - | 1.08 | 0.83-1.41 | 0.547 |
| Platelet count ( every 100 x 106/L) | - | - | 0.46 | 0.27-0.78 | 0.004 |
| Hemoglobin (every 1 g/dL) | - | - | 0.41 | 0.21-0.79 | 0.008 |
| Variables . | n . | % of PHT . | AOR . | 95% CI of AOR . | p-value . |
|---|---|---|---|---|---|
| Age (every 10 years) | - | - | 2.02 | 1.00-4.08 | 0.05 |
| Age of first blood transfusion (every 1 year) | - | - | 1.04 | 0.97-1.12 | 0.209 |
| Sex, (%) | |||||
| Female | 125 | 37.50 | 0.14 | 0.03-0.53 | 0.004 |
| Male | 94 | 62.50 | 1 | referent | - |
| Splenectomy, (%) | |||||
| No | 134 | 33.33 | 1 | referent | - |
| Yes | 85 | 66.67 | 306.87 | 14.01-6720.66 | <0.001 |
| Genotype group | |||||
| 1) β-thalassemia | 140 | 87.50 | 9.47 | 1.16-77.34 | 0.036 |
| 2) α-thalassemia and combined α and β-thalassemia | 79 | 12.50 | 1 | referent | - - |
| Nucleated RBC/100 WBC (every 100 nucleated RBC) | - | - | 1.08 | 0.83-1.41 | 0.547 |
| Platelet count ( every 100 x 106/L) | - | - | 0.46 | 0.27-0.78 | 0.004 |
| Hemoglobin (every 1 g/dL) | - | - | 0.41 | 0.21-0.79 | 0.008 |
Author notes
Asterisk with author names denotes non-ASH members.
