?-THALASSEMIA INTERMEDIA IN CHILDREN AND ADOLESCENTS: ? CHAIN GENOTYPE IN RELATION TO DISEASE PHENOTYPE AND PULMONARY HYPERTENSION
(Abstract release date: 05/19/16)
EHA Library. Ragab I. 06/09/16; 135049; PB2149
Assoc. Prof. Iman Ragab
Contributions
Contributions
Abstract
Abstract: PB2149
Type: Publication Only
Background
Prediction of β-thalassemia intermedia (BTI) phenotype from the genotype remains problematic.
Aims
Our aim is to study the different β-chain mutations in a group of Egyptian patients with BTI, its impact on clinical presentation, laboratory parameters and complications laying stress on pulmonary hypertension.
Methods
A cross-sectional study including 37 patients with BTI was performed in Pediatric Hematology Clinic, Children’s Hospital, Ain Shams University. Revision of hospital records for age of diagnosis, blood transfusion, frequency, transfusion index over the last year and recording of complications as pubertal delay, gall stones, leg ulcers together with splenectomy status and hydroxyurea treatment was performed. Physical examination for weight and height standard deviation scores, liver and spleen size then calculation of clinical score. Laboratory investigations included complete blood picture, initial hemoglobin electrophoresis, total, direct bilirubin, LDH, s.ferritin and β-Chain mutation analysis. 35 patients underwent echocardiography with recording of tricuspid regurgitant jet velocity and estimation of right ventricular systolic pressure.
Results
The studied patients had mean age of 10.3 ± 4.55 years (range 4-18), female/male 20 /1.7, mean age at diagnosis 4.14 ± 1.77 years (range 2-8), 10 (27.0%) had been diagnosed less than the age of 3 years, 19 (51.4%) between 3-6 years, 8 (21.6%) from 6-8 years, with a mean hemoglobin 6.38 ± 1.26 gm/dl (4 – 10). Positive consanguinity was detected in 14 (37.8%) patients and positive family history in 20 (54.1%). 18 (48.6%) became transfusion dependent (TD), 9 (22.5%) patients had never been transfused, 8 (20.0%) receive one or two yearly transfusion, 23 (57.5%) receive more than two transfusions per year. Transfusion index ranged from 38 – 186 cc/kg/year in the TD group. Their mean height SDS -0.81 ± 1.17; 75.7% of them had no obvious thalassemic facies, and5.4% had definite facies. Mild Pubertal delay was present in 16.22% and advanced delay in 5.41%. Splenectomy was performed in 5 (13.5%) patients; 64.86% were on hydroxyurea therapy.As regards β-chain genotype results, 14 (37.84%) have compound heterozygous with IVS1.6/codon6 and IVS1.6/ IVS1.1and IVS1.1/codon2.7 most frequent genotypes, 10(27.03%) had heterozygous with IVS1.1 mutation most common, and 13 (35.14%) have homozygous mutations with IVS1.6 the commonest mutation with no significant difference between the three groups as regards age at diagnosis, hemoglobin at diagnosis. Mean pretransfusion hemoglobin was higher in heterozygous 8.90 ±1.29 gm/dl compared to compound heterozygous 7.29±0.61 gm/dl and homozygous 7.92±0.49 gm/dl.As Regards pulmonary hypertension (PHTN), Patients with PHTN had higher total serum bilirubin 2.15 ± 0.71mg/dl, higher LDH 515.21 ± 190.86IU/L, serum ferritin 1757.00 ng/ml (1082 – 2239), reticulocyte count 3.13 ± 1.05% compared to those with normal pulmonary pressure 1.55 ± 0.56 mg/ml, P=.009, 333.55 ± 96.00 IU/L, P=0.001, 576.00 (296 – 1716) ng/ml, P=0.042; 2.45 ± 0.55%, P=0.019 respectively; while they had lower initial hemoglobin level 6.41 ± 1.43 gm/dl P=0.008. Compound heterozygotes formed 57.1%, heterozygotes 14.3% and homozygote mutations 28.6% of patients with PHTN compared to 30%, 30% and 40% in patients without PHTN, P=0.267.
Conclusion
Compound heterozygous are the most frequent β-chain genotype in patients with β-TI and it presents with more severe hemolysis and more frequent pulmonary hypertension.
Session topic: E-poster
Keyword(s): Pulmonary hypertension, Thalassemia
Type: Publication Only
Background
Prediction of β-thalassemia intermedia (BTI) phenotype from the genotype remains problematic.
Aims
Our aim is to study the different β-chain mutations in a group of Egyptian patients with BTI, its impact on clinical presentation, laboratory parameters and complications laying stress on pulmonary hypertension.
Methods
A cross-sectional study including 37 patients with BTI was performed in Pediatric Hematology Clinic, Children’s Hospital, Ain Shams University. Revision of hospital records for age of diagnosis, blood transfusion, frequency, transfusion index over the last year and recording of complications as pubertal delay, gall stones, leg ulcers together with splenectomy status and hydroxyurea treatment was performed. Physical examination for weight and height standard deviation scores, liver and spleen size then calculation of clinical score. Laboratory investigations included complete blood picture, initial hemoglobin electrophoresis, total, direct bilirubin, LDH, s.ferritin and β-Chain mutation analysis. 35 patients underwent echocardiography with recording of tricuspid regurgitant jet velocity and estimation of right ventricular systolic pressure.
Results
The studied patients had mean age of 10.3 ± 4.55 years (range 4-18), female/male 20 /1.7, mean age at diagnosis 4.14 ± 1.77 years (range 2-8), 10 (27.0%) had been diagnosed less than the age of 3 years, 19 (51.4%) between 3-6 years, 8 (21.6%) from 6-8 years, with a mean hemoglobin 6.38 ± 1.26 gm/dl (4 – 10). Positive consanguinity was detected in 14 (37.8%) patients and positive family history in 20 (54.1%). 18 (48.6%) became transfusion dependent (TD), 9 (22.5%) patients had never been transfused, 8 (20.0%) receive one or two yearly transfusion, 23 (57.5%) receive more than two transfusions per year. Transfusion index ranged from 38 – 186 cc/kg/year in the TD group. Their mean height SDS -0.81 ± 1.17; 75.7% of them had no obvious thalassemic facies, and5.4% had definite facies. Mild Pubertal delay was present in 16.22% and advanced delay in 5.41%. Splenectomy was performed in 5 (13.5%) patients; 64.86% were on hydroxyurea therapy.As regards β-chain genotype results, 14 (37.84%) have compound heterozygous with IVS1.6/codon6 and IVS1.6/ IVS1.1and IVS1.1/codon2.7 most frequent genotypes, 10(27.03%) had heterozygous with IVS1.1 mutation most common, and 13 (35.14%) have homozygous mutations with IVS1.6 the commonest mutation with no significant difference between the three groups as regards age at diagnosis, hemoglobin at diagnosis. Mean pretransfusion hemoglobin was higher in heterozygous 8.90 ±1.29 gm/dl compared to compound heterozygous 7.29±0.61 gm/dl and homozygous 7.92±0.49 gm/dl.As Regards pulmonary hypertension (PHTN), Patients with PHTN had higher total serum bilirubin 2.15 ± 0.71mg/dl, higher LDH 515.21 ± 190.86IU/L, serum ferritin 1757.00 ng/ml (1082 – 2239), reticulocyte count 3.13 ± 1.05% compared to those with normal pulmonary pressure 1.55 ± 0.56 mg/ml, P=.009, 333.55 ± 96.00 IU/L, P=0.001, 576.00 (296 – 1716) ng/ml, P=0.042; 2.45 ± 0.55%, P=0.019 respectively; while they had lower initial hemoglobin level 6.41 ± 1.43 gm/dl P=0.008. Compound heterozygotes formed 57.1%, heterozygotes 14.3% and homozygote mutations 28.6% of patients with PHTN compared to 30%, 30% and 40% in patients without PHTN, P=0.267.
Conclusion
Compound heterozygous are the most frequent β-chain genotype in patients with β-TI and it presents with more severe hemolysis and more frequent pulmonary hypertension.
Session topic: E-poster
Keyword(s): Pulmonary hypertension, Thalassemia
Abstract: PB2149
Type: Publication Only
Background
Prediction of β-thalassemia intermedia (BTI) phenotype from the genotype remains problematic.
Aims
Our aim is to study the different β-chain mutations in a group of Egyptian patients with BTI, its impact on clinical presentation, laboratory parameters and complications laying stress on pulmonary hypertension.
Methods
A cross-sectional study including 37 patients with BTI was performed in Pediatric Hematology Clinic, Children’s Hospital, Ain Shams University. Revision of hospital records for age of diagnosis, blood transfusion, frequency, transfusion index over the last year and recording of complications as pubertal delay, gall stones, leg ulcers together with splenectomy status and hydroxyurea treatment was performed. Physical examination for weight and height standard deviation scores, liver and spleen size then calculation of clinical score. Laboratory investigations included complete blood picture, initial hemoglobin electrophoresis, total, direct bilirubin, LDH, s.ferritin and β-Chain mutation analysis. 35 patients underwent echocardiography with recording of tricuspid regurgitant jet velocity and estimation of right ventricular systolic pressure.
Results
The studied patients had mean age of 10.3 ± 4.55 years (range 4-18), female/male 20 /1.7, mean age at diagnosis 4.14 ± 1.77 years (range 2-8), 10 (27.0%) had been diagnosed less than the age of 3 years, 19 (51.4%) between 3-6 years, 8 (21.6%) from 6-8 years, with a mean hemoglobin 6.38 ± 1.26 gm/dl (4 – 10). Positive consanguinity was detected in 14 (37.8%) patients and positive family history in 20 (54.1%). 18 (48.6%) became transfusion dependent (TD), 9 (22.5%) patients had never been transfused, 8 (20.0%) receive one or two yearly transfusion, 23 (57.5%) receive more than two transfusions per year. Transfusion index ranged from 38 – 186 cc/kg/year in the TD group. Their mean height SDS -0.81 ± 1.17; 75.7% of them had no obvious thalassemic facies, and5.4% had definite facies. Mild Pubertal delay was present in 16.22% and advanced delay in 5.41%. Splenectomy was performed in 5 (13.5%) patients; 64.86% were on hydroxyurea therapy.As regards β-chain genotype results, 14 (37.84%) have compound heterozygous with IVS1.6/codon6 and IVS1.6/ IVS1.1and IVS1.1/codon2.7 most frequent genotypes, 10(27.03%) had heterozygous with IVS1.1 mutation most common, and 13 (35.14%) have homozygous mutations with IVS1.6 the commonest mutation with no significant difference between the three groups as regards age at diagnosis, hemoglobin at diagnosis. Mean pretransfusion hemoglobin was higher in heterozygous 8.90 ±1.29 gm/dl compared to compound heterozygous 7.29±0.61 gm/dl and homozygous 7.92±0.49 gm/dl.As Regards pulmonary hypertension (PHTN), Patients with PHTN had higher total serum bilirubin 2.15 ± 0.71mg/dl, higher LDH 515.21 ± 190.86IU/L, serum ferritin 1757.00 ng/ml (1082 – 2239), reticulocyte count 3.13 ± 1.05% compared to those with normal pulmonary pressure 1.55 ± 0.56 mg/ml, P=.009, 333.55 ± 96.00 IU/L, P=0.001, 576.00 (296 – 1716) ng/ml, P=0.042; 2.45 ± 0.55%, P=0.019 respectively; while they had lower initial hemoglobin level 6.41 ± 1.43 gm/dl P=0.008. Compound heterozygotes formed 57.1%, heterozygotes 14.3% and homozygote mutations 28.6% of patients with PHTN compared to 30%, 30% and 40% in patients without PHTN, P=0.267.
Conclusion
Compound heterozygous are the most frequent β-chain genotype in patients with β-TI and it presents with more severe hemolysis and more frequent pulmonary hypertension.
Session topic: E-poster
Keyword(s): Pulmonary hypertension, Thalassemia
Type: Publication Only
Background
Prediction of β-thalassemia intermedia (BTI) phenotype from the genotype remains problematic.
Aims
Our aim is to study the different β-chain mutations in a group of Egyptian patients with BTI, its impact on clinical presentation, laboratory parameters and complications laying stress on pulmonary hypertension.
Methods
A cross-sectional study including 37 patients with BTI was performed in Pediatric Hematology Clinic, Children’s Hospital, Ain Shams University. Revision of hospital records for age of diagnosis, blood transfusion, frequency, transfusion index over the last year and recording of complications as pubertal delay, gall stones, leg ulcers together with splenectomy status and hydroxyurea treatment was performed. Physical examination for weight and height standard deviation scores, liver and spleen size then calculation of clinical score. Laboratory investigations included complete blood picture, initial hemoglobin electrophoresis, total, direct bilirubin, LDH, s.ferritin and β-Chain mutation analysis. 35 patients underwent echocardiography with recording of tricuspid regurgitant jet velocity and estimation of right ventricular systolic pressure.
Results
The studied patients had mean age of 10.3 ± 4.55 years (range 4-18), female/male 20 /1.7, mean age at diagnosis 4.14 ± 1.77 years (range 2-8), 10 (27.0%) had been diagnosed less than the age of 3 years, 19 (51.4%) between 3-6 years, 8 (21.6%) from 6-8 years, with a mean hemoglobin 6.38 ± 1.26 gm/dl (4 – 10). Positive consanguinity was detected in 14 (37.8%) patients and positive family history in 20 (54.1%). 18 (48.6%) became transfusion dependent (TD), 9 (22.5%) patients had never been transfused, 8 (20.0%) receive one or two yearly transfusion, 23 (57.5%) receive more than two transfusions per year. Transfusion index ranged from 38 – 186 cc/kg/year in the TD group. Their mean height SDS -0.81 ± 1.17; 75.7% of them had no obvious thalassemic facies, and5.4% had definite facies. Mild Pubertal delay was present in 16.22% and advanced delay in 5.41%. Splenectomy was performed in 5 (13.5%) patients; 64.86% were on hydroxyurea therapy.As regards β-chain genotype results, 14 (37.84%) have compound heterozygous with IVS1.6/codon6 and IVS1.6/ IVS1.1and IVS1.1/codon2.7 most frequent genotypes, 10(27.03%) had heterozygous with IVS1.1 mutation most common, and 13 (35.14%) have homozygous mutations with IVS1.6 the commonest mutation with no significant difference between the three groups as regards age at diagnosis, hemoglobin at diagnosis. Mean pretransfusion hemoglobin was higher in heterozygous 8.90 ±1.29 gm/dl compared to compound heterozygous 7.29±0.61 gm/dl and homozygous 7.92±0.49 gm/dl.As Regards pulmonary hypertension (PHTN), Patients with PHTN had higher total serum bilirubin 2.15 ± 0.71mg/dl, higher LDH 515.21 ± 190.86IU/L, serum ferritin 1757.00 ng/ml (1082 – 2239), reticulocyte count 3.13 ± 1.05% compared to those with normal pulmonary pressure 1.55 ± 0.56 mg/ml, P=.009, 333.55 ± 96.00 IU/L, P=0.001, 576.00 (296 – 1716) ng/ml, P=0.042; 2.45 ± 0.55%, P=0.019 respectively; while they had lower initial hemoglobin level 6.41 ± 1.43 gm/dl P=0.008. Compound heterozygotes formed 57.1%, heterozygotes 14.3% and homozygote mutations 28.6% of patients with PHTN compared to 30%, 30% and 40% in patients without PHTN, P=0.267.
Conclusion
Compound heterozygous are the most frequent β-chain genotype in patients with β-TI and it presents with more severe hemolysis and more frequent pulmonary hypertension.
Session topic: E-poster
Keyword(s): Pulmonary hypertension, Thalassemia
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