POSSIBLE RISK FACTORS FOR THROMBOSIS IN CHINESE PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA
(Abstract release date: 05/19/16)
EHA Library. Long Z. 06/09/16; 132557; E1008
Dr. Zhangbiao Long
Contributions
Contributions
Abstract
Abstract: E1008
Type: Eposter Presentation
Background
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease caused by an acquired mutation of the X-linked PIGA gene on the hematopoietic stem cell. The most common cause of morbidity and mortality in PNH is thrombosis, but the exact mechanisms involved in thrombus formation are still unknown, and predisposing factors for thrombosis in PNH patients have yet to be defined.
Aims
To identify high risk factors and susceptibility genes leading to thrombotic formation in PNH.
Methods
Totally, 95 patients with PNH diagnosed between 2009 and 2015 were enrolled in the study. Clinical data like sex, age, hemoglobin level, reticular cell percentage, white blood cell and platelet count, LDH level, CD59- and FLAER-granulocytes percentage, thrombophilia risk factors like level of protein C, protein S, antithrombin III, APC resistance, blood fat, phospholipid antibody were evaluated. Samples from patients were genotyped for the reported 28 alleles in 21 genes including MTHFR, PROC, PROS, F2, F5, prothrombin and other genes which are reported as high risk factors for venous thromboembolism (VTE) by polymerase chain reaction fragment length polymorphism methods (PCR-RFLP).
Results
Of the 95 PNH patients, 19 (20%) patients had at least 1 episode of thrombotic event. Only 3 patients had arterial thrombosis and 16 patients had venous thrombosis. The medium age of patients with thrombosis was 42-year-old, similar to those without (42-year-old, p=0.9947). Male : female ratio was 1.71 in thrombosis group, 1.17 in non-thrombosis group (p=0.6072). Patients with thrombosis had the same disease pattern compared to those without. Although there was no difference in level of hemoglobin (p=0.2512), white blood cell count (p=0.4681), platelet count(p=0.6185), reticular cell count (p=0.6296)and LDH level (p=0.4511) between patients with thrombosis and those without, patients with thrombosis showed higher percentage of CD59- granulocytes ( p=0.038 )and FLAER- granulocytes (p=0.036) compared to those without. The routine thrombophilia screening tests did not show any difference either between PNH patients and normal controls, or between patients with or without thrombosis. Patients with the TC genotype (rs2519093 in the ABO gene) were approximately 18.5 folds prone to thrombus formation than those with the CC genotype ( p<0.0001 ). In addition, the T allele was found to be a significant risk factor for thrombosis (OR 6.447, 95%CI 2.815-14.76, p<0.0001). No association was detected between other SNPs and risk to thrombosis.
Conclusion
Compared with non-thrombotic patients, PNH thrombotic patients have similar clinical features except that they have bigger PNH clone. And for the first time, our results suggested that the rs2519093 in the ABO gene confers risk to thrombosis in PNH. Therefore, rs2519093 polymorphism may represent a potential genetic biomarker in PNH patients for thrombus formation.
Session topic: E-poster
Keyword(s): Gene polymorphism, PNH, Risk factor, Thrombosis
Type: Eposter Presentation
Background
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease caused by an acquired mutation of the X-linked PIGA gene on the hematopoietic stem cell. The most common cause of morbidity and mortality in PNH is thrombosis, but the exact mechanisms involved in thrombus formation are still unknown, and predisposing factors for thrombosis in PNH patients have yet to be defined.
Aims
To identify high risk factors and susceptibility genes leading to thrombotic formation in PNH.
Methods
Totally, 95 patients with PNH diagnosed between 2009 and 2015 were enrolled in the study. Clinical data like sex, age, hemoglobin level, reticular cell percentage, white blood cell and platelet count, LDH level, CD59- and FLAER-granulocytes percentage, thrombophilia risk factors like level of protein C, protein S, antithrombin III, APC resistance, blood fat, phospholipid antibody were evaluated. Samples from patients were genotyped for the reported 28 alleles in 21 genes including MTHFR, PROC, PROS, F2, F5, prothrombin and other genes which are reported as high risk factors for venous thromboembolism (VTE) by polymerase chain reaction fragment length polymorphism methods (PCR-RFLP).
Results
Of the 95 PNH patients, 19 (20%) patients had at least 1 episode of thrombotic event. Only 3 patients had arterial thrombosis and 16 patients had venous thrombosis. The medium age of patients with thrombosis was 42-year-old, similar to those without (42-year-old, p=0.9947). Male : female ratio was 1.71 in thrombosis group, 1.17 in non-thrombosis group (p=0.6072). Patients with thrombosis had the same disease pattern compared to those without. Although there was no difference in level of hemoglobin (p=0.2512), white blood cell count (p=0.4681), platelet count(p=0.6185), reticular cell count (p=0.6296)and LDH level (p=0.4511) between patients with thrombosis and those without, patients with thrombosis showed higher percentage of CD59- granulocytes ( p=0.038 )and FLAER- granulocytes (p=0.036) compared to those without. The routine thrombophilia screening tests did not show any difference either between PNH patients and normal controls, or between patients with or without thrombosis. Patients with the TC genotype (rs2519093 in the ABO gene) were approximately 18.5 folds prone to thrombus formation than those with the CC genotype ( p<0.0001 ). In addition, the T allele was found to be a significant risk factor for thrombosis (OR 6.447, 95%CI 2.815-14.76, p<0.0001). No association was detected between other SNPs and risk to thrombosis.
Conclusion
Compared with non-thrombotic patients, PNH thrombotic patients have similar clinical features except that they have bigger PNH clone. And for the first time, our results suggested that the rs2519093 in the ABO gene confers risk to thrombosis in PNH. Therefore, rs2519093 polymorphism may represent a potential genetic biomarker in PNH patients for thrombus formation.
Session topic: E-poster
Keyword(s): Gene polymorphism, PNH, Risk factor, Thrombosis
Abstract: E1008
Type: Eposter Presentation
Background
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease caused by an acquired mutation of the X-linked PIGA gene on the hematopoietic stem cell. The most common cause of morbidity and mortality in PNH is thrombosis, but the exact mechanisms involved in thrombus formation are still unknown, and predisposing factors for thrombosis in PNH patients have yet to be defined.
Aims
To identify high risk factors and susceptibility genes leading to thrombotic formation in PNH.
Methods
Totally, 95 patients with PNH diagnosed between 2009 and 2015 were enrolled in the study. Clinical data like sex, age, hemoglobin level, reticular cell percentage, white blood cell and platelet count, LDH level, CD59- and FLAER-granulocytes percentage, thrombophilia risk factors like level of protein C, protein S, antithrombin III, APC resistance, blood fat, phospholipid antibody were evaluated. Samples from patients were genotyped for the reported 28 alleles in 21 genes including MTHFR, PROC, PROS, F2, F5, prothrombin and other genes which are reported as high risk factors for venous thromboembolism (VTE) by polymerase chain reaction fragment length polymorphism methods (PCR-RFLP).
Results
Of the 95 PNH patients, 19 (20%) patients had at least 1 episode of thrombotic event. Only 3 patients had arterial thrombosis and 16 patients had venous thrombosis. The medium age of patients with thrombosis was 42-year-old, similar to those without (42-year-old, p=0.9947). Male : female ratio was 1.71 in thrombosis group, 1.17 in non-thrombosis group (p=0.6072). Patients with thrombosis had the same disease pattern compared to those without. Although there was no difference in level of hemoglobin (p=0.2512), white blood cell count (p=0.4681), platelet count(p=0.6185), reticular cell count (p=0.6296)and LDH level (p=0.4511) between patients with thrombosis and those without, patients with thrombosis showed higher percentage of CD59- granulocytes ( p=0.038 )and FLAER- granulocytes (p=0.036) compared to those without. The routine thrombophilia screening tests did not show any difference either between PNH patients and normal controls, or between patients with or without thrombosis. Patients with the TC genotype (rs2519093 in the ABO gene) were approximately 18.5 folds prone to thrombus formation than those with the CC genotype ( p<0.0001 ). In addition, the T allele was found to be a significant risk factor for thrombosis (OR 6.447, 95%CI 2.815-14.76, p<0.0001). No association was detected between other SNPs and risk to thrombosis.
Conclusion
Compared with non-thrombotic patients, PNH thrombotic patients have similar clinical features except that they have bigger PNH clone. And for the first time, our results suggested that the rs2519093 in the ABO gene confers risk to thrombosis in PNH. Therefore, rs2519093 polymorphism may represent a potential genetic biomarker in PNH patients for thrombus formation.
Session topic: E-poster
Keyword(s): Gene polymorphism, PNH, Risk factor, Thrombosis
Type: Eposter Presentation
Background
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease caused by an acquired mutation of the X-linked PIGA gene on the hematopoietic stem cell. The most common cause of morbidity and mortality in PNH is thrombosis, but the exact mechanisms involved in thrombus formation are still unknown, and predisposing factors for thrombosis in PNH patients have yet to be defined.
Aims
To identify high risk factors and susceptibility genes leading to thrombotic formation in PNH.
Methods
Totally, 95 patients with PNH diagnosed between 2009 and 2015 were enrolled in the study. Clinical data like sex, age, hemoglobin level, reticular cell percentage, white blood cell and platelet count, LDH level, CD59- and FLAER-granulocytes percentage, thrombophilia risk factors like level of protein C, protein S, antithrombin III, APC resistance, blood fat, phospholipid antibody were evaluated. Samples from patients were genotyped for the reported 28 alleles in 21 genes including MTHFR, PROC, PROS, F2, F5, prothrombin and other genes which are reported as high risk factors for venous thromboembolism (VTE) by polymerase chain reaction fragment length polymorphism methods (PCR-RFLP).
Results
Of the 95 PNH patients, 19 (20%) patients had at least 1 episode of thrombotic event. Only 3 patients had arterial thrombosis and 16 patients had venous thrombosis. The medium age of patients with thrombosis was 42-year-old, similar to those without (42-year-old, p=0.9947). Male : female ratio was 1.71 in thrombosis group, 1.17 in non-thrombosis group (p=0.6072). Patients with thrombosis had the same disease pattern compared to those without. Although there was no difference in level of hemoglobin (p=0.2512), white blood cell count (p=0.4681), platelet count(p=0.6185), reticular cell count (p=0.6296)and LDH level (p=0.4511) between patients with thrombosis and those without, patients with thrombosis showed higher percentage of CD59- granulocytes ( p=0.038 )and FLAER- granulocytes (p=0.036) compared to those without. The routine thrombophilia screening tests did not show any difference either between PNH patients and normal controls, or between patients with or without thrombosis. Patients with the TC genotype (rs2519093 in the ABO gene) were approximately 18.5 folds prone to thrombus formation than those with the CC genotype ( p<0.0001 ). In addition, the T allele was found to be a significant risk factor for thrombosis (OR 6.447, 95%CI 2.815-14.76, p<0.0001). No association was detected between other SNPs and risk to thrombosis.
Conclusion
Compared with non-thrombotic patients, PNH thrombotic patients have similar clinical features except that they have bigger PNH clone. And for the first time, our results suggested that the rs2519093 in the ABO gene confers risk to thrombosis in PNH. Therefore, rs2519093 polymorphism may represent a potential genetic biomarker in PNH patients for thrombus formation.
Session topic: E-poster
Keyword(s): Gene polymorphism, PNH, Risk factor, Thrombosis
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