Assessing adequacy of blood transfusions and clinical outcomes in children with Thalassemia.

Published: Last Edited:

This essay has been submitted by a student. This is not an example of the work written by our professional essay writers.


1. Title of the Study; Assessing adequacy of blood transfusions and clinical outcomes in children with Thalassemia.

2. A summary of the proposed research in lay/non-technical language;

The Thalassemias are hereditary disorders of haemoglobin, inherited in a mendelian recessive way, resulting in defective systhesis of the globin chains of the molecule. (Weatherall, 2001) TheThalassemiasyndrome is classified according to which of the globin chains is affected. The two main groups are the Alpha (α) and Beta (β) Thalassemias, resulting from an inadequate production of the most abundant globin chains in the haemoglobin molecule, the alpha and beta chains respectively. (Journal of the American Society of Hematology, 2011) Clinically, Thalassemias are classified as Major, Minor and Intermedia. I) Thalassemia Minor includes heterozygous phenotypes of α and β Thalassemias, also known as α and β Thalassemia Traits. These patients, having only one defective globulin gene, are healthy carriers and do not have significant anaemia. But their red blood cells are microcytic and are variable in shape. II) Thalassemia Major is the most severe one. It includes homozygous phenotypes of β Thalassemia, also referred as, β Thalassemia Major, which produces severe anaemia and many serious complications and patients require lifelong regular blood transfusions. III) Thalassemia Intermedia includes mild β mutations and a form of α thalassemia known as Hb H disease. Initially patients are not transfusion-dependent and receive infrequent blood transfusions. But as their age increases, their spleen enlarges or after an acute infection, the transfusions may become regular. (Thalassemia Internation Fereration, 2012) Hence, this study is intended to assess the adequacy of blood transfusions in children having Thalassemia Major or Intermedia. As soon as ethical clearance would be approved by the Ministry Of Health and Quality Of Life, parents of these transfusion-dependent Thalassemia children from the Victoria Hospital and Jawaharlal Nehru Hospital, will be asked for their consent to allow their wards to take part in the study. On receiving their consent, the following variables will be measured for each of the child : -Age, Gender -Type of Transfusion-dependent Thalassemia ( Major or Intermedia ) -Weight, -Height, -Growth and development, -Size of splenomegaly or if the child has undergone splenectomy, -Facial deformities or any structural changes, -clinical status at the time of transfusion, -Pre-Transfusion Haemoglobin and Haematocrit (Hct), -Serum Ferritin, Then, the Blood Volume will be calculated for each patient as regards to the above variables. The ‘Post-Transfusion’ Haemoglobin will also be measured. The interval between blood transfusions and the volume and age of the blood transfused should also be known. An adequate blood transfusion therapy will give a post-transfusion Hb of 13-14 g/dl, and maintain a pre-transfusion Hb at 9-10 g/dl.

3. A clear statement of the justification for the study, its significance in development and in meeting the needs of the country/population in which the research is carried out;

Transfusion is the mainstay of treatment of Thalassemia Major and Intermedia, and it is often a lifelong process. It is important for Transfusion to be adequate for the following reasons: I) To prevent ineffective erythropoiesis and meet the need for oxygen supply, II) To ensure proper growth and development, III)To prevent development of bone deformities of the face and brittle bones, IV)To prevent Splenomegaly and Hepatomegaly, and Heart complications. (Thalassemia International Federation, 2008) As per the Thalassemia Register of Mauritius, there are around 100 Thalassemia patients who are Transfusion-dependent. Since there are no dedicated Thalassemia-centres for the management of these patients, they are currently being managed in regional hospitals and private clinics. A standard protocol for the management of Thalassemia was established by the Ministry Of Health and Quality of life, in collaboration with the Thalassemia Society. Hence, this study will be undertaken to see whether the transfusion requirements of transfusion-dependent thalassemia children are being met in the two hospitals mentioned above, whether they are being transfused adequately to ensure proper growth and development, prevent any complications and undesired clinical outcomes and whether there is adherence to the Protocol as far as transfusion is concerned.

4. Summary of all previous studies on the topic, including unpublished studies known to the investigators and sponsors, and information on all previously published research on the topic.

In Mauritius no such study has been undertaken so far. In 2009, N. Shah et al. studied the ‘Effectiveness of transfusion program in thalassemia major patients receiving multiple blood transfusions at a transfusion centre in Western India’. Data were obtained from 142 beta-thalassemia major patients aged atleast 3 years. Considering having a Pre-transfusion Haemoglobin level of 9-10gm/dl as being adequately transfused, 53.5 % of the patients were found to be under transfused due to large intervals between successive blood transfusions. It was also concluded that the disease worsen with increasing age and thus transfusion requirements increase. (Asian Journal of Transfusion Science, 2010) Modell et al carried out a study on “Total management of Thalassemia Major “ in 1977, which comprised of 196 individuals with thalassaemia major between 1 and 23 years old. Since splenomegaly assiociated with hypersplenism, is common in Thalassemia patients and it considerably increases blood transfusion requirements as a result of a high rate of hemolysis, splenectomy must be done to significantly reduce the blood requirements. It was found that thalassemia patients who did not have their spleen removed, had a blood requirement between 200 and 1200 ml/kg per year, while splenectomisedpatients had a blood requirement between 150 and 350 ml/ kg per year. This concluded that there was a drastic reduction in blood transfusion requirements following splenectomy. (Archives of disease in childhood,1977) R.Gayer et al. studied the ‘Long-term effect of splenectomy on transfusion requirements in 16 patients with thalassemia major for 2–17 years post-splenectomy’ to investigate whether the decrease in transfusion requirements post-surgery was permanent. It was indeed seen that the transfusion requirements remained almost constant, showing that splenectomy had a long-term effect on blood requirements. (American Journal of Haematology, 1989) 5. The objectives of the trial or study, its hypotheses or research questions, its assumptions, and its variables; Reduced oxygen delivery due to defective Haemoglobin synthesis affects growth and development in children suffering from thalassemia. An adequate and sufficient blood transfusion is therefore important to maintain the oxygen delivering capacity of blood and proper growth and development in these children. Hence the main objective of the study is to see whether blood transfusions being given to thalassemia children are adequate and correlate this with their clinical outcomes. The aim is also to identify the variables that need to be measured to ensure adequacy of blood transfusions. 6. A brief description of the design of the trial or study;

This study will be done in children attending Victoria Hospital and Jawarharlal Nehru Hospital following clearance from the ethical committee and will include a retrospective and prospective arm. As soon as ethical clearance will be obtained from the Ministry of Health and Quality of Life, a combination of a prospective and retrospective study will be carried out. Parents of transfusion-dependent thalassemia children, will each be given an information sheet containing a summary of the research project and will be asked for their consent to allow their wards to participate in the study. They will be asked to sign a participation consent form if they do agree to participate. They should know that the participation will be purely voluntary and anonymous, and most importantly, they may withdraw from the project at any time. To maintain anonymity throughout the study, each child will be assigned a reference number. After having the consent of the parents, for each child, his age and gender will be recorded because to compare growth and development, age and sex matched controls are important where the only variable is transfusion dependency. The type of Thalassemia (Major or Intermedia) , their respective weight and height will be recorded. The child’s age, sex, and measurements of weight and length or height will be used to calculate the following growth indicators : - length/height-for-age - weight-for-age -weight-for-length/height -BMI (body mass index)-for-age The pre-transfusion Haemoglobin and Haematocrit, serum ferritin and post-transfusion Haemoglobin of the child will then measured. The blood volume for each patient will then be calculated as per his requirements. If the spleen of the child is enlarged, the size of splenomegaly will also be measured and if the child has already undergone splenectomy, it should be mentioned. The clinical status of the children at the time transfusion should be recorded and any facial deformities or structural changes should be noted. The interval between blood transfusions and the volume and age of the blood transfused should also be known. It is also important to record the Haemoglobin and Haematocrit of the transfused blood. These are all the variables which may affect blood transfusion requirements. For each patient, the above mentioned variables will be measured and recorded to carry out the prospective study. A retrospective analysis will also be carried out by going through the previous records of the child. Then we will investigate whether the blood transfusions that were given to the child were adequate and whether this had affected his growth and development. If the transfusions were found to be inadequate, we would see whether this had any effects on the clinical outcomes of the child, and think about the possible clinical outcomes in the future and ways to avoid them. For a child who has come for the first time or on his appointment for blood transfusion, the prospective study would primarily involve monitoring his pre-transfusion haemoglobin, the volume of blood transfused, post-transfusion haemoglobin, and his growth and development in addition to the other variables mentioned above. The child will then be followed and on his next appointment, his pre-transfusion haemoglobin will again be measured prior to transfusion. The interval between consecutive transfusions is very important. According to our ‘Standard Protocols and Guidelines for Management of Thalassemia’ established by the Ministry of Health and Quality of Life in collaboration with the Thalassemia society, an adequate blood transfusion therapy should give a post-transfusion Haemoglobin of 13-14 g/dl and maintain a pre-transfusion Haemoglobin at 9-10 g/dl. Hence if on the second appointment, the pre transfusion haemoglobin of the patient is less than 9 g/dl, it means that the transfusion is inadequate and we will have to investigate what caused the inadequacy. Necessary adjustments would then be made so that on the third appointment, a pre-transfusion haemoglobin of 9-10 g/dl is maintained. At the end of the study, after 6 months, the growth and development of the child will again be measured to correlate it to adequacy of blood transfusions. 7. The number of research subjects needed to achieve the study objective and how this was statistically determined; After having the approval of their parents, all children will be taken from both hospitals.

8. The criteria for inclusion or exclusion of potential subjects and justification for the exclusion of any groups on the basis of age, sex, social or economic factors, or for other reasons; Only children with transfusion-dependent Thalassemia Major and Intermedia will be included.

Adults and children with other hemoglobinopathies will be excluded from the study.

9. Clinical and laboratory tests and other tests that are to be carried out;

- Full Blood Count (FBC) test on the child before and after transfusion to determine the pre and post transfusion Haemoglobin and Haematocrit. - Blood volume of each child will be calculated. - Growth and development will be measured at the start and at the end of the study. - A serum ferritin test will also be done. - Hb/Hct and blood volume of the transfused unit will be measured. 10. The potential benefits of the research to subjects and to others;

This study will help to identify the variables required to individualise the blood transfusion and improve transfusion management of Thalassemia patients. 11. The expected benefits of the research to the population, including new knowledge that the study might generate;

This research will not only benefit thalassemia patients but also other haemoglobinopathies in the long-run as far as hematological management is concerned. 12. Plans to inform subjects about the results of the study;

Not applicable.

13. A list of references cited in the protocol;

1. COHEN, A., GAYER, R. AND MIZANIN,J., 1989. Long-term effect of splenectomy on transfusion requirements in thalassemia major. American Journal of Haematology [online].30(4), 254-256. Available from: [Accessed 30 July 2013] 2. MODELL, B.,1977. Total Management of Thalassemia Major. Archives of Diseases in Childhood [online]. 52, 489-500. Available from: -0063.pdf [Accessed 24 July 2013]

3. RACHMILEWITZ, E.R. AND GIARDINA,P.J.,2011. How I treat Thalassemia. Blood Journal of the American Society of Haematology [online],118 (13), 3479-3488. Available from: sid=ff15a643-fa8c- 4118-a038-f417df9e1f5d#ref-33 [Accessed 30 July 2013 ] 4. SHAH, N., MISHRA, A., CHAUHAN, D., VORA, C. AND SHAH, N.R.,2010. Study of effectiveness on transfusion program in thalassemia major patients receiving multiple blood transfusions at a transfusion centre in Western India. Asian Journal of Transfusion Science [online], 4(2), 94–98. Available from: [Accessed 27 July 2013] 5. THALASSEMIA INTERNATIONAL FEDERATION, 2008. Guidelines for the Clinical Management of Thalassemia 2nd Revised ed [online]. Cyprus : Thalassemia International Federation. Available from: Guidelines-2nd-edition-revised-ENGLISH-lo.pdf [ Accessed July 2013 ] 6. THALASSEMIA INTERNATIONAL FEDERATION, 2012. Emergency Management of Thalassemia [online]. Cyprus : Thalassemia International Federation. Available from: _%CE%92%CE%9F%CE%9F%CE%9A-_FINAL.pdf [ Accessed June 2013 ] 7. WEATHERALL, D.J., 2001. The Thalassemias. Encyclopedia of life sciences [online].Nature Publishing Group. Available from: classe_(pdf)/revisionsPDF/Thalassaemias.pdf [Accessed 31 July 2013]

14. The time schedule for completion of study;

The time schedule of the study will be from September 2013 up to February 2014.

15. The source and amount of the research. In case of sponsorships, an account of the sponsor’s financial commitments to the research institution, the investigators, the research subjects, and when relevant the community;

The research project will not require any sponsorship.