TRANSIENT ELASTOGRAPHY (TE) IS A USEFUL TOOL FOR ASSESSING THE RESPONSE OF LIVER IRON CHELATION IN SICKLE CELL DISEASE PATIENTS
Main Article Content
Keywords
sickle cell disease, iron overload, chelation, Transient Elastography
Abstract
Sickle cell disease patients often need regular blood transfusions to improve both the quality of life and survival from the veno-occlusive complications of the disease. Deferasirox, a convenient long acting oral agent, has recently been introduced in clinical practice with promising efficacy.
This study aims to evaluate the association of liver stiffness and possible fibrosis with iron deposition and confirm the use of elastography as a validated test of responding to chelation with low cost and easy access.
15 patients with sickle cell disease and systemic or occasional transfusionswere evaluated with MRI,transient elastography and biochemistry, for liver iron(LIC) and liver stiffness(LSM) before onset and one year after taking Deferasirox.All patients completed the study.
Our results showed improvement in hepatic iron and hepatic stiffness after chelation therapy; Furthermore ALT, AST, LDH and ferritin levels have improved after 12 months of therapy with deferasirox.During the study no serious adverse events were encountered indicating the safety of the drug.
Transient liver elastography findings correlate with serum ferritin and LIC in patients with sickle cell disease and it is a useful tool for assessing the response of liver iron chelation therapy.
Keywords: Sickle cell disease, iron chelation, transient elastography, transfusion, iron overload
Downloads
Download data is not yet available.
Abstract 1119
PDF Downloads 555
HTML Downloads 122
References
1.Tanaka, Chiaki. "Clinical pharmacology of deferasirox." Clinical pharmacokinetics 53.8 (2014): 679-694.
---------------------------------------------------------------------------------
2.Marsella, Maria, and Caterina Borgna-Pignatti. "Transfusional iron overload and iron chelation therapy in thalassemia major and sickle cell disease." Hematology/Oncology Clinics 28.4 (2014): 703-727.
----------------------------------------------------------------------------------
3. Porter, John, and Maciej Garbowski. "Consequences and management of iron overload in sickle cell disease." ASH Education Program Book 2013.1 (2013): 447-456.
----------------------------------------------------------------------------------
4. Banerjee, Subhas, Charles Owen, and Sanjiv Chopra. "Sickle cell hepatopathy." Hepatology 33.5 (2001): 1021-1028.
----------------------------------------------------------------------------------
5. Telfer, P. T., et al. "Hepatic iron concentration combined with long?term monitoring of serum ferritin to predict complications of iron overload in thalassaemia major." British journal of haematology 110.4 (2000): 971-977.
----------------------------------------------------------------------------------
6. De LéDinghen, Victor, and Julien Vergniol. "Transient elastography for the diagnosis of liver fibrosis." Expert review of medical devices 7.6 (2010): 811-823.
----------------------------------------------------------------------------------
7. Fraquelli, Mirella, et al. "Transient elastography in the assessment of liver fibrosis in adult thalassemia patients." American journal of hematology 85.8 (2010): 564-568.
----------------------------------------------------------------------------------
8. Mirault, Tristan, et al. "Non?invasive assessment of liver fibrosis by transient elastography in post transfusional iron overload." European journal of haematology 80.4 (2008): 337-340.
----------------------------------------------------------------------------------
9. Miyazawa, Keisuke, et al. "A safety, pharmacokinetic and pharmacodynamic investigation of deferasirox (Exjade®, ICL670) in patients with transfusion-dependent anemias and iron-overload: a Phase I study in Japan." International journal of hematology 88.1 (2008): 73.
----------------------------------------------------------------------------------
10. Cappellini, M. D., et al. "Long-Term Safety and Tolerability of the Once-Daily, Oral Iron Chelator Deferasirox (Exjade®, ICL670) in Patients with Transfusional Iron Overload." (2006): 1768-1768.
----------------------------------------------------------------------------------
11. Wanko, Sam O., and Marilyn J. Telen. "Transfusion management in sickle cell disease." Hematology/oncology clinics of North America 19.5 (2005): 803-826.
----------------------------------------------------------------------------------
12. Kozanoglu, Ilknur, et al. "Automated red cell exchange procedures in patients with sickle cell disease." Transfusion and apheresis science 36.3 (2007): 305-312.
---------------------------------------------------------------------------------
13. Miller, Scott T., et al. "Impact of chronic transfusion on incidence of pain and acute chest syndrome during the Stroke Prevention Trial (STOP) in sickle-cell anemia." The Journal of pediatrics 139.6 (2001): 785-789.
---------------------------------------------------------------------------------
14. Hankins, Jane, et al. "Chronic transfusion therapy for children with sickle cell disease and recurrent acute chest syndrome." Journal of pediatric hematology/oncology 27.3 (2005): 158-161.
----------------------------------------------------------------------------------
15. Park, Dongyoun Deborah, et al. "Sickle Cell Disease and the Adherence to Guidelines for Use of Blood Transfusions." (2017): 4652-4652.
---------------------------------------------------------------------------------
16. Harmatz, Paul, et al. "Severity of iron overload in patients with sickle cell disease receiving chronic red blood cell transfusion therapy." Blood 96.1 (2000): 76-79.
----------------------------------------------------------------------------------
17. Wahl, Shannon, and Keith C. Quirolo. "Current issues in blood transfusion for sickle cell disease." Current opinion in pediatrics 21.1 (2009): 15-21.
----------------------------------------------------------------------------------
18. Olivieri, Nancy F. "Progression of iron overload in sickle cell disease." Seminars in hematology. Vol. 38. WB Saunders, 2001.
----------------------------------------------------------------------------------
19. Wood, John C., et al. "Myocardial iron loading in transfusion-dependent thalassemia and sickle cell disease." Blood 103.5 (2004): 1934-1936.
----------------------------------------------------------------------------------
20. Raghupathy, Radha, Deepa Manwani, and Jane A. Little. "Iron overload in sickle cell disease." Advances in hematology 2010 (2010).
---------------------------------------------------------------------------------
21. Allard, S., et al. "Monday 20th April 2015 Free Communication Transfusion Medicine and Nursing." transfusion 14.18 (2015): 18.
-------------------------------------------------------------------------------
22. Porter, John B. "Pathophysiology of transfusional iron overload: contrasting patterns in thalassemia major and sickle cell disease." Hemoglobin 33.sup1 (2009): S37-S45.
--------------------------------------------------------------------------------
23. Adamkiewicz, Thomas V., et al. "Serum ferritin level changes in children with sickle cell disease on chronic blood transfusion are nonlinear and are associated with iron load and liver injury." Blood 114.21 (2009): 4632-4638.
---------------------------------------------------------------------------------
24. Wood, John C., and Nilesh Ghugre. "Magnetic resonance imaging assessment of excess iron in thalassemia, sickle cell disease and other iron overload diseases." Hemoglobin 32.1-2 (2008): 85-96.
---------------------------------------------------------------------------------
25. Adamkiewicz, Thomas V., et al. "Serum ferritin level changes in children with sickle cell disease on chronic blood transfusion are nonlinear and are associated with iron load and liver injury." Blood 114.21 (2009): 4632-4638.
----------------------------------------------------------------------------------
26. Musallam, Khaled M., et al. "Cross-talk between available guidelines for the management of patients with beta-thalassemia major." Acta haematologica 130.2 (2013): 64-73.
---------------------------------------------------------------------------------
27. Fung, Ellen B., et al. "Disparity in the management of iron overload between patients with sickle cell disease and thalassemia who received transfusions." Transfusion 48.9 (2008): 1971-1980.
---------------------------------------------------------------------------------
28. Vichinsky, Elliott, et al. "Efficacy and safety of deferasirox compared with deferoxamine in sickle cell disease: Two?year results including pharmacokinetics and concomitant hydroxyurea." American journal of hematology 88.12 (2013): 1068-1073.
----------------------------------------------------------------------------------
29. El Alfy, Moshen, et al. "The safety, tolerability, and efficacy of a liquid formulation of deferiprone in young children with transfusional iron overload." Journal of pediatric hematology/oncology 32.8 (2010): 601-605.
----------------------------------------------------------------------------------
30. Vichinsky, Elliott, et al. "Long?term safety and efficacy of deferasirox (Exjade®) for up to 5 years in transfusional iron?overloaded patients with sickle cell disease." British journal of haematology 154.3 (2011): 387-397.
---------------------------------------------------------------------------------
31. Cappellini, Maria Domenica, et al. "Tailoring iron chelation by iron intake and serum ferritin: the prospective EPIC study of deferasirox in 1744 patients with transfusion-dependent anemias." haematologica 95.4 (2010): 557-566.
---------------------------------------------------------------------------------
32. Brittenham, Gary M., et al. "Noninvasive methods for quantitative assessment of transfusional iron overload in sickle cell disease." Seminars in hematology. Vol. 38. WB Saunders, 2001.
---------------------------------------------------------------------------------
33. Ballas, Samir K., et al. "Beyond the definitions of the phenotypic complications of sickle cell disease: an update on management." The Scientific World Journal 2012 (2012).
---------------------------------------------------------------------------------
34. Sinakos, Emmanouil, et al. "Is liver stiffness really unrelated to liver iron concentration?." British journal of haematology 150.2 (2010): 247-248.
----------------------------------------------------------------------------------
35. Ou, George, et al. "Utility of Transient Elastography in Estimating Hepatic Iron Concentration in Comparison to Magnetic Resonance Imaging in Patients Who are Transfusion-Dependent: A Canadian Center Experience." Hemoglobin 41.1 (2017): 21-25.
---------------------------------------------------------------------------------
36. Voskaridou, Ersi, et al. "Liver transient elastography (FibroScan) correlates with liver iron concentration and reflects liver fibrosis in patients with sickle cell disease." (2010): 1646-1646.
---------------------------------------------------------------------------------
37. Berry, Philip A., et al. "Hepatic dysfunction in sickle cell disease: a new system of classification based on global assessment." Clinical Gastroenterology and Hepatology 5.12 (2007): 1469-1476.
----------------------------------------------------------------------------------
38. Koh, Christopher, et al. "Liver stiffness increases acutely during sickle cell vaso?occlusive crisis." American journal of hematology 88.11 (2013).
----------------------------------------------------------------------------------
---------------------------------------------------------------------------------
2.Marsella, Maria, and Caterina Borgna-Pignatti. "Transfusional iron overload and iron chelation therapy in thalassemia major and sickle cell disease." Hematology/Oncology Clinics 28.4 (2014): 703-727.
----------------------------------------------------------------------------------
3. Porter, John, and Maciej Garbowski. "Consequences and management of iron overload in sickle cell disease." ASH Education Program Book 2013.1 (2013): 447-456.
----------------------------------------------------------------------------------
4. Banerjee, Subhas, Charles Owen, and Sanjiv Chopra. "Sickle cell hepatopathy." Hepatology 33.5 (2001): 1021-1028.
----------------------------------------------------------------------------------
5. Telfer, P. T., et al. "Hepatic iron concentration combined with long?term monitoring of serum ferritin to predict complications of iron overload in thalassaemia major." British journal of haematology 110.4 (2000): 971-977.
----------------------------------------------------------------------------------
6. De LéDinghen, Victor, and Julien Vergniol. "Transient elastography for the diagnosis of liver fibrosis." Expert review of medical devices 7.6 (2010): 811-823.
----------------------------------------------------------------------------------
7. Fraquelli, Mirella, et al. "Transient elastography in the assessment of liver fibrosis in adult thalassemia patients." American journal of hematology 85.8 (2010): 564-568.
----------------------------------------------------------------------------------
8. Mirault, Tristan, et al. "Non?invasive assessment of liver fibrosis by transient elastography in post transfusional iron overload." European journal of haematology 80.4 (2008): 337-340.
----------------------------------------------------------------------------------
9. Miyazawa, Keisuke, et al. "A safety, pharmacokinetic and pharmacodynamic investigation of deferasirox (Exjade®, ICL670) in patients with transfusion-dependent anemias and iron-overload: a Phase I study in Japan." International journal of hematology 88.1 (2008): 73.
----------------------------------------------------------------------------------
10. Cappellini, M. D., et al. "Long-Term Safety and Tolerability of the Once-Daily, Oral Iron Chelator Deferasirox (Exjade®, ICL670) in Patients with Transfusional Iron Overload." (2006): 1768-1768.
----------------------------------------------------------------------------------
11. Wanko, Sam O., and Marilyn J. Telen. "Transfusion management in sickle cell disease." Hematology/oncology clinics of North America 19.5 (2005): 803-826.
----------------------------------------------------------------------------------
12. Kozanoglu, Ilknur, et al. "Automated red cell exchange procedures in patients with sickle cell disease." Transfusion and apheresis science 36.3 (2007): 305-312.
---------------------------------------------------------------------------------
13. Miller, Scott T., et al. "Impact of chronic transfusion on incidence of pain and acute chest syndrome during the Stroke Prevention Trial (STOP) in sickle-cell anemia." The Journal of pediatrics 139.6 (2001): 785-789.
---------------------------------------------------------------------------------
14. Hankins, Jane, et al. "Chronic transfusion therapy for children with sickle cell disease and recurrent acute chest syndrome." Journal of pediatric hematology/oncology 27.3 (2005): 158-161.
----------------------------------------------------------------------------------
15. Park, Dongyoun Deborah, et al. "Sickle Cell Disease and the Adherence to Guidelines for Use of Blood Transfusions." (2017): 4652-4652.
---------------------------------------------------------------------------------
16. Harmatz, Paul, et al. "Severity of iron overload in patients with sickle cell disease receiving chronic red blood cell transfusion therapy." Blood 96.1 (2000): 76-79.
----------------------------------------------------------------------------------
17. Wahl, Shannon, and Keith C. Quirolo. "Current issues in blood transfusion for sickle cell disease." Current opinion in pediatrics 21.1 (2009): 15-21.
----------------------------------------------------------------------------------
18. Olivieri, Nancy F. "Progression of iron overload in sickle cell disease." Seminars in hematology. Vol. 38. WB Saunders, 2001.
----------------------------------------------------------------------------------
19. Wood, John C., et al. "Myocardial iron loading in transfusion-dependent thalassemia and sickle cell disease." Blood 103.5 (2004): 1934-1936.
----------------------------------------------------------------------------------
20. Raghupathy, Radha, Deepa Manwani, and Jane A. Little. "Iron overload in sickle cell disease." Advances in hematology 2010 (2010).
---------------------------------------------------------------------------------
21. Allard, S., et al. "Monday 20th April 2015 Free Communication Transfusion Medicine and Nursing." transfusion 14.18 (2015): 18.
-------------------------------------------------------------------------------
22. Porter, John B. "Pathophysiology of transfusional iron overload: contrasting patterns in thalassemia major and sickle cell disease." Hemoglobin 33.sup1 (2009): S37-S45.
--------------------------------------------------------------------------------
23. Adamkiewicz, Thomas V., et al. "Serum ferritin level changes in children with sickle cell disease on chronic blood transfusion are nonlinear and are associated with iron load and liver injury." Blood 114.21 (2009): 4632-4638.
---------------------------------------------------------------------------------
24. Wood, John C., and Nilesh Ghugre. "Magnetic resonance imaging assessment of excess iron in thalassemia, sickle cell disease and other iron overload diseases." Hemoglobin 32.1-2 (2008): 85-96.
---------------------------------------------------------------------------------
25. Adamkiewicz, Thomas V., et al. "Serum ferritin level changes in children with sickle cell disease on chronic blood transfusion are nonlinear and are associated with iron load and liver injury." Blood 114.21 (2009): 4632-4638.
----------------------------------------------------------------------------------
26. Musallam, Khaled M., et al. "Cross-talk between available guidelines for the management of patients with beta-thalassemia major." Acta haematologica 130.2 (2013): 64-73.
---------------------------------------------------------------------------------
27. Fung, Ellen B., et al. "Disparity in the management of iron overload between patients with sickle cell disease and thalassemia who received transfusions." Transfusion 48.9 (2008): 1971-1980.
---------------------------------------------------------------------------------
28. Vichinsky, Elliott, et al. "Efficacy and safety of deferasirox compared with deferoxamine in sickle cell disease: Two?year results including pharmacokinetics and concomitant hydroxyurea." American journal of hematology 88.12 (2013): 1068-1073.
----------------------------------------------------------------------------------
29. El Alfy, Moshen, et al. "The safety, tolerability, and efficacy of a liquid formulation of deferiprone in young children with transfusional iron overload." Journal of pediatric hematology/oncology 32.8 (2010): 601-605.
----------------------------------------------------------------------------------
30. Vichinsky, Elliott, et al. "Long?term safety and efficacy of deferasirox (Exjade®) for up to 5 years in transfusional iron?overloaded patients with sickle cell disease." British journal of haematology 154.3 (2011): 387-397.
---------------------------------------------------------------------------------
31. Cappellini, Maria Domenica, et al. "Tailoring iron chelation by iron intake and serum ferritin: the prospective EPIC study of deferasirox in 1744 patients with transfusion-dependent anemias." haematologica 95.4 (2010): 557-566.
---------------------------------------------------------------------------------
32. Brittenham, Gary M., et al. "Noninvasive methods for quantitative assessment of transfusional iron overload in sickle cell disease." Seminars in hematology. Vol. 38. WB Saunders, 2001.
---------------------------------------------------------------------------------
33. Ballas, Samir K., et al. "Beyond the definitions of the phenotypic complications of sickle cell disease: an update on management." The Scientific World Journal 2012 (2012).
---------------------------------------------------------------------------------
34. Sinakos, Emmanouil, et al. "Is liver stiffness really unrelated to liver iron concentration?." British journal of haematology 150.2 (2010): 247-248.
----------------------------------------------------------------------------------
35. Ou, George, et al. "Utility of Transient Elastography in Estimating Hepatic Iron Concentration in Comparison to Magnetic Resonance Imaging in Patients Who are Transfusion-Dependent: A Canadian Center Experience." Hemoglobin 41.1 (2017): 21-25.
---------------------------------------------------------------------------------
36. Voskaridou, Ersi, et al. "Liver transient elastography (FibroScan) correlates with liver iron concentration and reflects liver fibrosis in patients with sickle cell disease." (2010): 1646-1646.
---------------------------------------------------------------------------------
37. Berry, Philip A., et al. "Hepatic dysfunction in sickle cell disease: a new system of classification based on global assessment." Clinical Gastroenterology and Hepatology 5.12 (2007): 1469-1476.
----------------------------------------------------------------------------------
38. Koh, Christopher, et al. "Liver stiffness increases acutely during sickle cell vaso?occlusive crisis." American journal of hematology 88.11 (2013).
----------------------------------------------------------------------------------