Deferoxamine as an Alternative Treatment for Thalassemia - Essay Example

Deferoxamine as an Alternative Treatment for Thalassemia Order# 362605 3/30/2010 Student Deferoxamine as an alternative treatment for Thalassemia 1.0 Introduction Thalassemia Thalassemia is a genetic disease that affects the blood. It is the name accorded to a number of genetically acquired blood disorders which have an effect on the ability of the body to form the red cells in blood. The existence of this condition leads to a reduction in the rate at which globin chains responsible for the formation of haeomoglobin are synthesized. This in turn leads to an abnormal formation of haemoglobin molecules leading to anaemia which is a major symptom of thalassaemia. In the condition of thalassemia, the synthesis of globins is very low while in anaemia on the other hand the synthesized globin does not function correctly( Stanly, 2010). Depending on its severity, thalassemia can be defined as minor, intermedia or major. The symptoms of this condition especially in children include irritability, vomiting, stunted growth, sleepiness and lack of the ability to thrive. These symptoms are related to the anaemia severity. Lack of effective erythropoiesis leads to hyper metabolism in a patient causing fever, severe as well as lack of effective treatment for this disease may be characterized by hepatosplenomegaly. Growth retardation and iron overload are two common problems present even when the patient is receiving treatment (Patricia, et al, 2010). An estimate of about one thousand people in the United States suffers from thalassemia while the number of carriers remains unknown. Thalassemia has been found to have a certain trait that helps in protecting against malaria but to a certain degree, making it to selectively have a survival advantage on a number of carriers (Patricia, et al, 2010).. While patients suffering from thalassemia minor do not need any kind of treatment, those with the major type of thalassemia are treated using transfusion therapy, allogeneic hematopoietic transplantation, splenectomy as well as iron chelation or use of a medical drug called deferoxamine. This essay is intended at determining the veracity of the main argument aimed at efficacy of deferoxamine in preventing complications of iron overload in thalassemia patients (Patricia, et al, 2010). 2.0 Condition/aspect overview The main characteristics of thalasaemia include congenital abnormality during the synthesis of globulin chain, severe anemia and lack of effective erythropoiesis. Treatment of this condition is based on iron chelatin therapy as a result of iron overload and on constant blood transfusions. The use of chelation therapy for the treatment of thalassemia has escalated a lot of debate between different health professionals whereby some highly support its use while other are against some of the effects of its use ( Radak,2010). According to Radak, (2010) iron overload prevention in the thalassemia patients can be obtained through external intervention. It is very likely that patients suffering from thalassemia get accumulations of iron in the pancreases, liver and cardiac muscles. Deferoxamine is a good option to infuse for the prevention of such undesirable deposits in the blood of the thalassemia patients. Investigations have been made into the synthesis and treatment potentials of Deferoxamine In their chemical reviews and noted that this is a bacterial sideirthore which is produced by actino-bacteria of streptomycespilsus. This bacterial deduction is also called DFOB, DFOK and Desferal. There are many medical applications of this agent (Radak, 2010). Gonikbere, E. (2010) argued that the most important one is a chelating agent which is normally used for the removal of excess iron from the body. The commercially available salt of Desferal which is originally Deferoxamine is Meyslate salt (Samavat & Modell, 2005). Historically Deferoxamine has been used in treating the iron poisoning of acute nature in infants and small children. This agent has also been used for the treatment of a disease in which iron excess in the body can be genetic or later acquired. In some of the parents who have acute Anemia and who require many blood transfusions, the author has suggested that iron accumulation in their bodies becomes natural and Deferoxamine has been provided in the form of injections that are given daily after every six hours. It is interesting to know that Doctors in Iran developed the first tablet of Deferoxamine in 2009. The use of tablets and capsules replaced the inject able drugs that were previously used. Deferoxamine also effectively acts in the treatment of patients who have got Aluminum toxicity. The medicine has been approved by FDA. A study on the Deferoxamine which was concluded in 2008 has suggested that the Deferoxamine speedily heals up the fractures in bone structures (Samavat & Modell, 2005). 3.0 Methods Secondary data analysis has been done on the basis of following inter-alia and by using the most recent articles on the subject of thalassemia. The articles are peer reviewed and therefore very reliable. They present information that is both in support and those that oppose the use deferoxamine as a treatment for thalassemia.The following key words have been used: hematology, chelatin agents, thalassemia, iron overload, diabetes and Deferoxamine. 4.0 Discussion Support Iron overload occurs with the increase in absorption. Patients who do not receive any transfusions increase their own absorption of dietary iron by 2 to 5 grams annually. Regular transfusions excessively increase this level of iron to above 10grams in every year (Patricia, Griffith and Farrell, 2010). The presence of this excess iron as iron deposits in the body organs and tissues such as the liver and muscle tissues can lead to endocrinopathy that is accompanied by disorders such as thyroid, diabetes, pituitary and adrenal complication, fibrosis and even organ failure. Treating a patient through the use of deferoxamine therefore allows one to effectively get rid of excess of these deposits and in turn protect him or her from these harmful disorders (Borgana, et al, 2008). The use of deferoxamine has led to a considerable decrease in the levels of morbidity and mortality as a result of iron overload in thalassemia patients. In patients especially children suffering from microcytic-hypochromic anaemia and whose response to iron has failed, deposits and addition of iron will only make the situation worse (Zurlo , Stephano & Pignatti ,2005). According to Kamata, Takahashi and Miyagima (2007) and British National Formulary (2008) Deferoxamine lowers the impact of iron accumulation in the RBCs, liver, cardiac muscles and pancreas. The over accumulation of Deferoxamine changes the color of urine into pinkish red, Since, the RBCs after blood transfusion and iron chelating become over loaded with the heavy element of iron this medicine makes digestible and drainable compounds with the excessive iron and relieves the body and body parts from the excess iron. Lee and Kim, (2007) are also in support of deferoxamine use in the treatment of thalassemia. According to these authors, Thalassemia major patients are vulnerable to Diabetes Mellitus because of less number of RBCs or their distorted position in the blood stream. Therefore, Deferoxamine chemically acts with the excessive iron in the RBCs and pancreas, thus, allowing oxygen and glucose to flow into the tissues in a better manner (Lee, and Kim, 2007). John, et al (2010) experimented with the efficacy of Deferoxamine in preventing complications of iron over load in thalassemia major through an experiment with fifty nine patients. These were from 7 years to thirty one year’s of age. There were 29 males and 30 female patients. These patients were evaluated periodically after every 5 years till their death. The method used was a detailed clinical and laboratory evaluation at each follow up visit that measured iron stores in the liver with a very well calculated and scientific magnetic device. During this study Patricia, Griffith and Farrell (2010) argued that the body iron accumulated burden which was evaluated and assessed by the magnetic device was very closely related to the proportionate ratio of cumulative transfusion iron to the cumulative Deferoxamine used in milli-moles of iron per kg of iron weight. Every increase in one unit of Deferoxamine was associated with the increased rate of glucose tolerance, resulting into Diabetes Mellitus, cardiac diseases and death. Nine people died during the study that used the chelation therapy quite late and did not use the Deferoxamine in proper proportion to the transfusion iron load. In relation to this experiment, Britten, (2010) at the department of medicine Case Western Reserve University Cleveland had said that On the basis above experiment scientifically based upon laboratory and clinical estimations investigation, evaluation and co-relation it was determined that the proper and earlier usage of Deferoxamine in the exact and proportional amount of the transfusion iron load, definitely reduces the body iron burden and naturally protects against the Diabetes mellitus in patients with thalassemia major (Barosi and Tura, 2009). In the clinical trials and observations Dudley, (2010) have further acclaimed the efficacy of another replica of Deferoxamine called Deferasirox for prevention and reduction of cardiac diseases in iron over load Beta thalassemia. They have reported that iron cardiac over load mostly causes death in patients. They had experimented with 192 patients while administering Deferasirox for one year. A magnetic resonance mayo-cordial fraction was used to evaluate the patients. This study showed that Deferasirox was an effective agent in removing and preventing the mayo-cordial iron in the thalassemia major patients. This has been reported in annual review of medicine and pathology. Other than getting rid of excess iron in the body organs and tissues, the use of deferoxamine and other chelation agents reduces the risks associated with constant blood transfusions. Such risks include hepatitis B as well as C. The acquisition of such blood borne ailments occurs despite the fact that blood should be screened for all known infections before transfusion (John et al, 2010). An evaluation done by Olivieri et al. (2007) on a specimen of liver biopsy from thalassemia patients who had received treatment with deferopine concluded that use of the drug resulted to fibrosis in every five of fourteen patients. Inadequacy in chelation therapy prior to taking the drug was found to be a major factor that resulted to the development of the fibrosis in the patients. Cirrhosis and fibrosis are two common conditions in thalassemia patients. This fact is well illustrated by one fact that three out of very eighteen patients suffered from cirrhosis prior their use of deferopine for treatment. 4 of 5 of these patients had hepatitis C virus antibodies, a major cause of thalassemia (Töndury, et al, 2008). The biopsy specimens studied by olivieri were later reviewed by a different histopathologist on behalf of Apotex, the company that manufactures deferopine. The assessment showed that most of the studied specimens were very inadequate thus no firm conclusions could be made (Olivieri et al. 2007). According to West wood, (2006) thalassemia helps in the protection of malaria in the affected patients who mainly live in humid regions where malaria is common. This means that the condition acts as an advantage as it confers selective survival on the carriers as well as well as perpetuating mutations. This fact makes thalassemia similar to sickle cell disease which is a genetic disorder that affects hemoglobin (West wood, 2006). Argument Though the use of deferoxamine has been found to have huge benefits especially in relation to iron over load and its prevention, controversy still arises with some medical personnel being against its use. The use of this drug has been found to cause toxicity. One such toxicity is a severe reaction that occurs at the site where the injection is done. A very high frequency loss of hearing ability has been noted in about thirty to forty percent of patients. Another possible occurrence is the night as well as color blindness. These complications are however reversible (Tesoriere , et al ,2006). In a previously done study by Olivieri et al (2007) the group of studied patients who used deferopine for treatment was either unwilling or unable to use deferoxamine. Under normal conditions, the presence of an iron overload would definitely be inevitable. This however wads not the case as only four of eighteen patients were found to have excess deposits of iron, the levels of iron had not changed in five patients whereas nine of the patients had the levels decrease. This showed that deferopine was also effective in getting rid of excess iron even in continuous transfusions (Olivieri et al, 2007). Stanly, (2010) at the department of hematology school of medicine Stanford University California has argued that Thalassemia patients are highly heterogeneous as far as their clinical severity is concerned. Their pathology and physiology in relation to their symptoms directly matches with the unmatched goblin chains. Therefore, alpha thalassemia patients are quite different from the beta thalassemia patients. However, two things are common with both types of the patients i.e. Red cell membrane is affected by the accumulation of separate goblin chain. A variety of thalassemia therefore exists (Stanly, 2010). 5.0 Conclusion Until the very recent of times, patients who used transfusion of blood to treat thalassemia did not make it past adolescence stage due to complications resulting from iron toxicity. The introduction and use of chelating substances to aid in the removal of excess iron has not only helped in reducing the level of mortality but also helped in increasing the life expectancy of patients (Emilio, et al. 2010). Most of the complications in thalassemia patients arise as a result of the deposition of excessive iron in the body organs and tissue hence requiring a treatment measure that will help in getting rid of this excessive iron to prevent opportunistic conditions such as liver failure and diabetes (Borgana, et al, 2008). Though the use of deferoxamine has been attributed to a number of complications such as blindness, loss of hearing among others, most of this are not only reversible but can also be prevented if all necessary precautions are put in place. These facts make the use of this agent in the treatment of thalassemia very appropriate and a method that should be adopted by all medical personnel (John, et al. 2010). Recommendations have been made to combine different therapies in the treatment of thalassemia in order to have the most successful effects. An example of such a recommendation involves the use of both deferoxamine and deferiprone. Use of these two drugs leads to an increase in the excretion of iron, a decrease in the level of ferritin and an improved glucose tolerance thus leading to reduced as well as reversed damage to the pancreas as a result of excess iron. Sanctus, V. and Zulu, E. (2007)also recommended that timely intervention with proper doses of the medicine Deferoxamine for lowering the iron load on the bodies of thalassemia major patients is necessary in order to prevent the auxiliary complications of thalassemia major. The alpha and beta thalassemia major patients show a variety of severity. The gender and age have also different complications at different stages. Hence it is very necessary that major findings about the symptoms, treatment and interventions should not be generalized in all the patients of thalassemia (Kamata, Takahashi and Miyagima, 2007). Hence, treatment of thalassemia with blood transfusion and iron chelation also needs appropriate, timely and adequate iron load reduction with intervention of Deferoxamine. 6.0 References Barosi, A. and Tura, S. 2009. Italian society of Hematology; practice guidelines for the management of iron overload in thalasemia major and related disorders. Italian institute of Hematology. 46: 9-12. Borgana, H. Pignatti C. Rasekhi, M. Naderifar, M. Bagheri, M.and Shahriari, H.2008. Survival studies in the symptomatic thalasemia. The Department of Pediatrics University of Ferrara Italy. 2: 8-9. British National Formulary. 2008.55:32 Britten, H. 2010. How to remain propionates with Deferoxamine; Scientific Review; The department of medicine Case Western Reserve University Cleveland. 6: 76-84. Dudley, A. and Gilan S. 2010. Efficacy of deferasirox in reducing and preventing cardiac iron overload in b-thalasemia England Journal of Medicine.91: 53-54 Emilio A, Giovanni D, Andrea Bacigalupo, Luca Malcovati, Emanuele Angelucci, Maria Teresa Van Lint, Michele Falda, Onida Fand Pioltelli P.2010. Prognostic impact of pre- transplantation transfusion history and secondary iron overload in patients with myelodysplastic syndrome undergoing allogeneic stem cell transplantation: a GITMO study. Haematological Jounal . 95: 476-484 Gonikbere, E. 2010. Effects of chelating agents: Deseferol. Int Med Journal of Science.3(5) :18. John, H, Nienhuis A, Snider M. and Merkel D. 2010. Efficacy of deferoxamine in preventing complications of iron overload in thalasemia major patients; England Journal of Medicine. 111: 42-67 Kamata, T, Takahashi, Y. and Miyajima, H. 2007.Use of desferrioxamine in the treatment of aceruloplasminemia. Ann. Neurol. 41: 404-407. Lee HJ, Lee SK and Kim. 2007. Differential regulation of iron chelator. Case Western University Cleveland. 188 : 45-56. Olivieri, N. Brittenham ,G. McLaren ,C.2007. Long-term safety and effectiveness of iron- chelation therapy with deferiprone for thalassemia major. N Engl J Med.339:417-423. Patricia M. Griffith, W. and. Farrell,D. 2010.Efficacy of Deferoxamine in Preventing Complications of Iron Overload in Patients with Thalassemia Major. 331 (9):567-573. Patricia, M. Gary M. Brittenham, C. and Griffith, W. 2010. Experimental estimation of iron overload in thalasemia majors .Medical Science lab overviews Journal. 34: 12-18. Radak, M. 2010. Prevention of Iron Overload in Thelassemia .Medline j. 117(16): 87-95) Samavat A, Modell B. 2006. Iranian national thalassaemia screening programme. BMJ. 329: 1134 – 1137. Samavat A, Modell B.2005. "Iranian national thalassaemia screening programme". BMJ (Clinical Research.) 329 (7475): 1134–7. Sanctus, V. and Zulu, E. 2007. 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