STATE OF THE ART
Managing thalassaemia- indian experience
Dr. Vanshree Singh, Director, Blood Bank, India Red Cross Society, 1, Red Cross Road, New Delhi 110 001
Thalassaemia is one of the major hereditary disorders involving haemogloblin in the human blood, which accounts for high mortality in childhood the name of a group of genetic blood disorders. It is a major clinical problem and unless supported by transfusion, children suffer from growth retardation and die at an early age from the profound effects of anemia. Currently, bone marrow transplantation from an HLA – identical sibling is the only therapy that offers a cure. Prenatal Diagnosis is possible by molecular analysis of DNA.
Thalassaemia and the haemoglobinopathies are a major health problem, placing an immeasurable emotional, psychological and economic burden on millions of people around the world. In the West, substantial progress has been made towards understanding the pathology of thalassaemia and its treatment. But the fact remains that the treatment of thalassaemia is a costly and painful process. In developing countries, knowledge of the disease remains sparse and treatment is an unaffordable luxury.
Globally, over 500,000 children with Hb disorders born annually 70% in middle and low resource countries. Out of which about 70% sickle cell anaemia and 30% thalassaemia syndromes. Less than 500,000 patients with Hb disorders are registered (living).
Thalassemia in India the prevalence shows the estimated number of thalassemics in India is 1,00,000. On an average 8 to 10 thousand thalassaemia majors born in India every year. Commonly found hemoglobinopathies are Beta thalassaemia major, Sickle cell disease, Hemoglobin E, HbD,Alpha thalassaemia & certain other hemoglobinopathies reported.Gene varies between 1–17% of population and mean prevalence of gene around 3%. Nearly, 30 million carriers live in our country. The prevalence high among Punjabis, Sindhis, Parsis, Bengalis & Gujratis.
Thalassemia is an inherited form of anaemia caused by faulty synthesis of hemoglobin. It is an inherited autosomal recessive blood disease. In thalassemia the genetic defect which could be either mutation or deletion, results in reduced rate of synthesis or no synthesis of one of the globulin chains that make up haemoglobin. This can use the formation of abnormal haemoglobin molecules, thus causing anaemia, the characteristic presenting symptom of the thalassemias. It is the most common form of disease present in the world. Doctors predict that by the end of 2050 this will be the most common health disease in the world and most of the patients will be from countries like India and china.
Role of indian red cross in the managing the thalassaemia cases
Indian Red Cross Society National Headquarters Blood Centre supports the 896 thalassaemics which contributes to 50% thalassaemics in the city. IRCS also support all over the country to prolong and improve the quality of the lives.
There are more than 500 children register in State Red Cross Blood centre (Gujarat, Hyderabad, Maharashtra) and Kelfer-oral iron chelating agent is provided free to all needy. Indian Red Cross Ahmedabad branch celebrating its 25 years of service for thalassemia children, by providing safe and adequate blood & iron chelation, Awareness through lectures in Colleges and Schools and Prevention program at Sanand by testing blood of pregnant women and terminate pregnancy if fetus is found to be thalassemia major.
The programme Started from 2008 up to 2009, 4800 samples (both from women and men) have been tested. Four fetuses found to be thalassemia major, were terminated with the consent of such couples, under Medical supervision. The population of Ahmedabad District, 70 lakhs is proposed to be included in the proposal. This will mean about 2.10,000 pregnant women are to be tested to know thalassemia minor status. In turn, about 10,500 men (spouse of these women) will also be covered under the test program. Cross Thalassemia CAP mission took up testing of 6000 pregnant women of Sanand Taluka in one year. 300 pregnant women were expected to be thalassemia minor and 5% of population being at risk. Out of these 300 couple it is expected that 15 couples may turn out to be thalassemia minor, where the woman is pregnant. One fetus has been terminated after investigations and confirmation that the fetus was found to be thalassemia major within the MTP Act.
Regular blood transfusion on a life long basis until a cure is available Transfusion regimes should aim to keep patients Hb levels at between 9–10.5 g/d1 before transfusion and not more than 15 g/d1 after transfusion. Screened Blood for hepatitis viruses B & C, HIV, Syphilis & Malaria and preferably washed packed red blood cells or leuco reduced packed red cells. Monitoring is most important.
Ideal blood transfusions
A unit of 250 ml packed red cells to be transfused every 3 to 4 weeks and blood transfusion to take place in Thalassemia Centre under proper medical care. No fresh blood or very old blood to be used and use filtered screened blood with regular Chelation
Many children die undiagnosed and even after diagnosis, death often occurs due to anemia, infection, cardiac failure. Not more than 10 to 15% of thalassaemia majors receive adequate treatment. The Cost of maintaining high 1–2 lacs per child per year ($ 2090.00–$ 4180.00). Good health services in metropolitan cities. There is No health Insurance for these patients’ good treating centers in some cities.
Threat is growing as it is estimated that about 60,000–70,000 are born each year world over with B-thalassaemia major. Out of which 8,000–10,000 are born each year in India (approx 20%). By 2020 the figure will reach 2,12,000 from 1,00,000.
Cure of thalassemia-
Stem cell transplantation
Stem Cell transplantation provides a thalassemia patient with healthy stem cells that will produce normal blood cells.
Stem Cells can be transplanted into a patient’s body through different methods, such as Bone Marrow Transplantation (Bmt). In BMT, chemotherapy is used to kill the patient’s stem cells in the bone marrow. They are then replaced with healthy stem cells from a compatible donor.
Cord blood transplantation
Instead of harvesting stem cells from a donors bone marrow or blood, stem cells are taken from the “cord blood” found in the umbilical cord/placenta of a newborn sibling. Unlike regular bone marrow transplantation, the stem cells taken from the cord blood do not have to be a perfect genetic match. There appears to be a lower instance of rejection in cord blood transplantation.
The objective of GENE therapy is to insert a normal beta - globin gene into the patient’s stem cells, thus allowing increased production of beta globin and healthy red blood cells.
Some drugs, including Hydroxyurea, can stimulate production of a third type of protein chain called gamma chains. In the womb, the fetus makes this type of protein instead of beta globin. It is not until after birth, when the fetus no longer produces gamma globin that the beta globin deficiency becomes apparent.
Hydroxyurea has been shown to induce production of fetal hemoglobin. Fetal hemoglobin has a pair of gamma-globin molecules in place of the typical beta-globins of adult hemoglobin. Higher-than-normal levels of fetal hemoglobin can ameliorate some of the symptoms of thalassemia. Effects in patients with -thalassemia major are controversial. We now report a marked elevation of total Hb levels with HU that permitted regular transfusions to be stopped in some children with transfusion-dependent -thalassemia.
It is Safe Blood transfusion, adaptation of National plan, access to free treatment and value of prevention is recognised.
In spite of high prevalence the counseling and health education regarding inherited disorder before marriage is required and needs to avoid the marriage between two traits. It is important that genetic counseling of the new born before birth for thalassaemia traits. Although, there are regular education programme to educate people about thalassaemia but more publication related to prevention, management and other aspects of thalassaemia are needed, as ignorance about thalasaemia is helping it to multiply faster.
Indian Red Society in the country involved in screening camps along with the blood donation camps, especially in Schools, Colleges where the young crowd are screened for thalasaemia trait.
Bone marrow transplantation or gene therapy may totally cure a case of thalassaemia major. But for all practical purposes transfusion with red cell concentrate in the only way to sustain the life of a thalassaemia child at present.