GROWTH DIFFERENTIATION FACTOR-15 IS ELEVATED IN PATIENTS WITH COMPOUND HETEROZYGOUS SICKLE CELL AND BETA-THALASSEMIA AND CORRELATES WITH HEMOLYSIS, ENDOTHELIAL DYSFUNCTION AND ANGIOGENESIS
(Abstract release date: 05/19/16)
EHA Library. Voskaridou E. 06/09/16; 133019; E1470
Dr. Ersi Voskaridou
Contributions
Contributions
Abstract
Abstract: E1470
Type: Eposter Presentation
Background
The clinical manifestations of Sickle Cell Disease (SCD) include episodes of vascular occlusion, chronic hemolytic anemia and frequent infections. SCD is also characterized by the presence of a chronic inflammatory state manifested by leukocytosis and monocytosis and increased circulating levels of pro-inflammatory cyto- and chemokines. Growth Differentiation Factor-15 (GDF-15), also known as macrophage inhibitory cytokine 1 (MIC-1) and non-steroidal anti-inflammatory drug-activated gene (NAG-1) is a member of the transforming growth factor- superfamily. Expression of the GDF-15 gene in cardiomyocytes, vascular smooth muscle cells, and endothelial cells is strongly upregulated in response to oxidative stress, inflammation and tissue injury. Increased GDF-15 concentrations have been associated with an adverse prognosis in patients with acute coronary syndromes and chronic heart failure.
Aims
The aim of this study was to evaluate the GDF-15 levels in patients with compound heterozygous SCD and beta-thalassemia (HbS/βthal) and to explore possible associations with disease features, such as hemolysis, inflammation, endothelial dysfunction and angiogenesis.
Methods
Seventy-five adult Caucasian patients with HbS/bthal were included in the study, while 20 healthy individuals served as controls. Patients with HbS/βthal divided in two groups: group A included 36 patients under hydroxycarbamide (HC+) treatment and group B included 39 patients without hydroxycarbamide (HC-) treatment. Along with hematology and blood chemistry parameters determination, measurements of circulating levels of GDF-15, hs-CRP, vWF-antigen, hs-TnT and Placental Growth Factor (PlGF) were measured in patients with HbS/βthal and controls using immunoenzymatic techniques.
Results
The main results of the study showed that: GDF-15 were elevated in patients with HbS/βthal compared to controls (1,980.7±159.8 vs 665.4±50.9 pg/mL, p<0.0001). Regarding hydroxycarbamide treatment, GDF-15 levels were elevated in (HC+) patients compared to (HC-) patients (2,478±222.6 vs 1,520±204.7 pg/mL, p=0.002), or 30/36 vs 21/39 patients with elevated GDF-15 levels (c2=0.002). GDF-15 levels correlated significantly with markers of erythropoiesis, such as Hb, HbF, ferritin and reticulocytes (r=-0.424, p<0.01; r=0.562, p<0.001; r=0.423, p<0.001 and r=0.510, p<0.001, respectively), with markers of hemolysis, such as LDH and uric acid (r=0.412, p<0.001 and r=0.321, p=0.005, respectively), and with markers of endothelial dysfunction and angiogenesis such as vWF-antigen and PlGF (r=0.238, p<0.05 and r=0.461, p<0.001, respectively). Surprisingly, no correlation was found between GDF-15 and hs-CRP levels (p>0.65).
Conclusion
These findings suggest a multifactorial role of GDF-15 in patients with HbS/βthal as it correlates with hemolysis, endothelial dysfunction and angiogenesis. The higher GDF-15 levels measured in patients treated with hydroxycarbamide may reflect a possible drug reaction. More studies are needed to clarify the exact role of GDF-15 in HbS/βthal.
Session topic: E-poster
Type: Eposter Presentation
Background
The clinical manifestations of Sickle Cell Disease (SCD) include episodes of vascular occlusion, chronic hemolytic anemia and frequent infections. SCD is also characterized by the presence of a chronic inflammatory state manifested by leukocytosis and monocytosis and increased circulating levels of pro-inflammatory cyto- and chemokines. Growth Differentiation Factor-15 (GDF-15), also known as macrophage inhibitory cytokine 1 (MIC-1) and non-steroidal anti-inflammatory drug-activated gene (NAG-1) is a member of the transforming growth factor- superfamily. Expression of the GDF-15 gene in cardiomyocytes, vascular smooth muscle cells, and endothelial cells is strongly upregulated in response to oxidative stress, inflammation and tissue injury. Increased GDF-15 concentrations have been associated with an adverse prognosis in patients with acute coronary syndromes and chronic heart failure.
Aims
The aim of this study was to evaluate the GDF-15 levels in patients with compound heterozygous SCD and beta-thalassemia (HbS/βthal) and to explore possible associations with disease features, such as hemolysis, inflammation, endothelial dysfunction and angiogenesis.
Methods
Seventy-five adult Caucasian patients with HbS/bthal were included in the study, while 20 healthy individuals served as controls. Patients with HbS/βthal divided in two groups: group A included 36 patients under hydroxycarbamide (HC+) treatment and group B included 39 patients without hydroxycarbamide (HC-) treatment. Along with hematology and blood chemistry parameters determination, measurements of circulating levels of GDF-15, hs-CRP, vWF-antigen, hs-TnT and Placental Growth Factor (PlGF) were measured in patients with HbS/βthal and controls using immunoenzymatic techniques.
Results
The main results of the study showed that: GDF-15 were elevated in patients with HbS/βthal compared to controls (1,980.7±159.8 vs 665.4±50.9 pg/mL, p<0.0001). Regarding hydroxycarbamide treatment, GDF-15 levels were elevated in (HC+) patients compared to (HC-) patients (2,478±222.6 vs 1,520±204.7 pg/mL, p=0.002), or 30/36 vs 21/39 patients with elevated GDF-15 levels (c2=0.002). GDF-15 levels correlated significantly with markers of erythropoiesis, such as Hb, HbF, ferritin and reticulocytes (r=-0.424, p<0.01; r=0.562, p<0.001; r=0.423, p<0.001 and r=0.510, p<0.001, respectively), with markers of hemolysis, such as LDH and uric acid (r=0.412, p<0.001 and r=0.321, p=0.005, respectively), and with markers of endothelial dysfunction and angiogenesis such as vWF-antigen and PlGF (r=0.238, p<0.05 and r=0.461, p<0.001, respectively). Surprisingly, no correlation was found between GDF-15 and hs-CRP levels (p>0.65).
Conclusion
These findings suggest a multifactorial role of GDF-15 in patients with HbS/βthal as it correlates with hemolysis, endothelial dysfunction and angiogenesis. The higher GDF-15 levels measured in patients treated with hydroxycarbamide may reflect a possible drug reaction. More studies are needed to clarify the exact role of GDF-15 in HbS/βthal.
Session topic: E-poster
Abstract: E1470
Type: Eposter Presentation
Background
The clinical manifestations of Sickle Cell Disease (SCD) include episodes of vascular occlusion, chronic hemolytic anemia and frequent infections. SCD is also characterized by the presence of a chronic inflammatory state manifested by leukocytosis and monocytosis and increased circulating levels of pro-inflammatory cyto- and chemokines. Growth Differentiation Factor-15 (GDF-15), also known as macrophage inhibitory cytokine 1 (MIC-1) and non-steroidal anti-inflammatory drug-activated gene (NAG-1) is a member of the transforming growth factor- superfamily. Expression of the GDF-15 gene in cardiomyocytes, vascular smooth muscle cells, and endothelial cells is strongly upregulated in response to oxidative stress, inflammation and tissue injury. Increased GDF-15 concentrations have been associated with an adverse prognosis in patients with acute coronary syndromes and chronic heart failure.
Aims
The aim of this study was to evaluate the GDF-15 levels in patients with compound heterozygous SCD and beta-thalassemia (HbS/βthal) and to explore possible associations with disease features, such as hemolysis, inflammation, endothelial dysfunction and angiogenesis.
Methods
Seventy-five adult Caucasian patients with HbS/bthal were included in the study, while 20 healthy individuals served as controls. Patients with HbS/βthal divided in two groups: group A included 36 patients under hydroxycarbamide (HC+) treatment and group B included 39 patients without hydroxycarbamide (HC-) treatment. Along with hematology and blood chemistry parameters determination, measurements of circulating levels of GDF-15, hs-CRP, vWF-antigen, hs-TnT and Placental Growth Factor (PlGF) were measured in patients with HbS/βthal and controls using immunoenzymatic techniques.
Results
The main results of the study showed that: GDF-15 were elevated in patients with HbS/βthal compared to controls (1,980.7±159.8 vs 665.4±50.9 pg/mL, p<0.0001). Regarding hydroxycarbamide treatment, GDF-15 levels were elevated in (HC+) patients compared to (HC-) patients (2,478±222.6 vs 1,520±204.7 pg/mL, p=0.002), or 30/36 vs 21/39 patients with elevated GDF-15 levels (c2=0.002). GDF-15 levels correlated significantly with markers of erythropoiesis, such as Hb, HbF, ferritin and reticulocytes (r=-0.424, p<0.01; r=0.562, p<0.001; r=0.423, p<0.001 and r=0.510, p<0.001, respectively), with markers of hemolysis, such as LDH and uric acid (r=0.412, p<0.001 and r=0.321, p=0.005, respectively), and with markers of endothelial dysfunction and angiogenesis such as vWF-antigen and PlGF (r=0.238, p<0.05 and r=0.461, p<0.001, respectively). Surprisingly, no correlation was found between GDF-15 and hs-CRP levels (p>0.65).
Conclusion
These findings suggest a multifactorial role of GDF-15 in patients with HbS/βthal as it correlates with hemolysis, endothelial dysfunction and angiogenesis. The higher GDF-15 levels measured in patients treated with hydroxycarbamide may reflect a possible drug reaction. More studies are needed to clarify the exact role of GDF-15 in HbS/βthal.
Session topic: E-poster
Type: Eposter Presentation
Background
The clinical manifestations of Sickle Cell Disease (SCD) include episodes of vascular occlusion, chronic hemolytic anemia and frequent infections. SCD is also characterized by the presence of a chronic inflammatory state manifested by leukocytosis and monocytosis and increased circulating levels of pro-inflammatory cyto- and chemokines. Growth Differentiation Factor-15 (GDF-15), also known as macrophage inhibitory cytokine 1 (MIC-1) and non-steroidal anti-inflammatory drug-activated gene (NAG-1) is a member of the transforming growth factor- superfamily. Expression of the GDF-15 gene in cardiomyocytes, vascular smooth muscle cells, and endothelial cells is strongly upregulated in response to oxidative stress, inflammation and tissue injury. Increased GDF-15 concentrations have been associated with an adverse prognosis in patients with acute coronary syndromes and chronic heart failure.
Aims
The aim of this study was to evaluate the GDF-15 levels in patients with compound heterozygous SCD and beta-thalassemia (HbS/βthal) and to explore possible associations with disease features, such as hemolysis, inflammation, endothelial dysfunction and angiogenesis.
Methods
Seventy-five adult Caucasian patients with HbS/bthal were included in the study, while 20 healthy individuals served as controls. Patients with HbS/βthal divided in two groups: group A included 36 patients under hydroxycarbamide (HC+) treatment and group B included 39 patients without hydroxycarbamide (HC-) treatment. Along with hematology and blood chemistry parameters determination, measurements of circulating levels of GDF-15, hs-CRP, vWF-antigen, hs-TnT and Placental Growth Factor (PlGF) were measured in patients with HbS/βthal and controls using immunoenzymatic techniques.
Results
The main results of the study showed that: GDF-15 were elevated in patients with HbS/βthal compared to controls (1,980.7±159.8 vs 665.4±50.9 pg/mL, p<0.0001). Regarding hydroxycarbamide treatment, GDF-15 levels were elevated in (HC+) patients compared to (HC-) patients (2,478±222.6 vs 1,520±204.7 pg/mL, p=0.002), or 30/36 vs 21/39 patients with elevated GDF-15 levels (c2=0.002). GDF-15 levels correlated significantly with markers of erythropoiesis, such as Hb, HbF, ferritin and reticulocytes (r=-0.424, p<0.01; r=0.562, p<0.001; r=0.423, p<0.001 and r=0.510, p<0.001, respectively), with markers of hemolysis, such as LDH and uric acid (r=0.412, p<0.001 and r=0.321, p=0.005, respectively), and with markers of endothelial dysfunction and angiogenesis such as vWF-antigen and PlGF (r=0.238, p<0.05 and r=0.461, p<0.001, respectively). Surprisingly, no correlation was found between GDF-15 and hs-CRP levels (p>0.65).
Conclusion
These findings suggest a multifactorial role of GDF-15 in patients with HbS/βthal as it correlates with hemolysis, endothelial dysfunction and angiogenesis. The higher GDF-15 levels measured in patients treated with hydroxycarbamide may reflect a possible drug reaction. More studies are needed to clarify the exact role of GDF-15 in HbS/βthal.
Session topic: E-poster
{{ help_message }}
{{filter}}