Introduction

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.

Methods

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.

Results

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).

Conclusion

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.

Abbreviation

Hb CS = Hemoglobin Constant spring, Hb Pakse´= Hemoglobin Pakse´

Abbreviation

PHT= pulmonary hypertension, AOR= adjusted odds ratio, 95% CI= 95% confidence interval

Disclosures:

No relevant conflicts of interest to declare.

Table 1.

Clinical characteristic data of 219 patients with thalassemia

CharacteristicsPatients (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 
CharacteristicsPatients (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 
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Table 2.

Multivariate analysis of the effect of genotype group on pulmonary hypertension in 219 patients with thalassemia

Variablesn% of PHTAOR95% CI of AORp-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 
Variablesn% of PHTAOR95% CI of AORp-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 
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Topics:
genotype, pulmonary hypertension, thalassemia, hemoglobin constant spring, echocardiography, hemoglobin, hartnup disease, splenectomy, blood transfusion, transfusion

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2013 by The American Society of Hematology
2013
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