Dr K K Koul
World Thalassaemia Day is Celebrated annually on the 8 th of May, with the aim of commemorating Thalassaemia patients who died as a result of the disease and encouraging those who are still alive and struggling with it daily. The theme of the event this year is “Empowering Lives, Embracing Progress: Equitable and Accessible Thalassaemia Treatment for All.” With an estimated 100 million (10 crore) people worldwide carrying genes responsible for Thalassaemia, and more than 300,000 Babies born annually with severe forms of the disease, International Thalassaemia Day is a powerful call to raise awareness about this condition and its impact while celebrating the solidarity of the resilient Thalassaemia community worldwide.
Panos Englezos, President and Founder of Thalassaemia International Federation (TIF) created this day in 1994 in the memory of his son George and other Thalassaemia patients who fought the disease bravely. Since then every year World Thalassaemia Day is Celebrated on May 08
George Hoyot Whipple, an American Pathologist (Noble Prize Winner) and W. L. Bradford (Prof. of Paediatrics) coined the term Thalassaemia in 1936 although first described by Thomas Benton Cooley, a Pediatrician in 1925 based on 5 cases of Italian and Greek descent and it was called Mediterranean anaemia / Cooley’s Anamia. It was later confirmed that the cases which Dr. Thomas Cooley had described were of beta Thalassaemia Major.
Thalassaemia is derived from Thalassa (Greek) meaning Sea and emia (latin) meaning blood and was called as Sea Blood / Mediterranean Anaemia as initial cases belonged to areas around Mediterranean Sea. In Greek mythology, Thalassa was the primordial Goddess of the Sea.
Thalassaemia Syndromes are a heterogeneous group of inherited anaemias characterized by defects in the synthesis of one or more of the globin chain subunits of the Hemoglobin (Hb) tetrammer. The clinical syndromes associated with Thalassaemia arise from the combined consequences of inadequate Hb production and imbalanced accumulation of globin subunits. The former causes hypochromia and microcytosis ; the latter leads to ineffective erythropoiesis (defective red blood cell precursors undergo cell death / apoptosis in bone marrow) and haemolytic anaemia (premature destruction of RBCs). Clinical manifestation are diverse, ranging from asymptomatic hypochromia and microcytosis to profound anaemia which can be fatal in utero or in early childhood if untreated. This heterogeneity arises from the variable severities of the primary biosynthetic defects and combined modifying factors. Due to turmoil in the bone marrow (Hyperplastic Marrow) the marrow expands which stretch the bones. With this and along with other disease related issues lead to marked craniofascial and orofacial deformities, protrusion of abdomen, marked liver and spleenic enlargement and other major problems. Palliative treatment of the severe forms by regular blood transfusion is eventually compromised by the concomitant problems of iron overload, alloimmunization and blood borne infections.
According to the Hb polypeptide chain whose synthesis is impaired, The Thalassaemias are called a (alpha), b (beta), y (gamma), (delta), (delta-beta) or (episilon, alfa beta gamma, delta-beta) Thalassaemias. From a clinical point of view the most relevent types are and thalassaemias, resulting from the absent or decrease synthesis of one of the two types of polypeptide chains (or) that form the normal adult human Hb molecule (HbA, a 2 b2). Alpha chains are encoded by globin gene clusters on chromosome 16 (two genes on each chromosome) and chains are encoded by globin gene cluster on chromosome 11 (one gene on each chromosome). Haem group (iron protoporphyrin IX) is same in all types of haemoglobins (HbA, HbF, HbA2 etc). HbA (Adult Hb) is present in RBCs and it transports oxygen from the lungs (alveoli) to all tissues and organs of the body and carries CO2 from the tissues back to lungs where it is exhaled. HbF (foetal Hb) is the predominant Hb of the baby during foetal life and its production automatically stops when the baby is born and instead HbA is produced which gradually becomes the predominant Hb by 6 months or in some cases by 9 months after the birth.
In Thalassaemia due to genetic defect, HbF production continues even after birth and HbA is not produced or is produced in small quantity only and the patients suffer from chronic anaemia with marked decrease in oxygen carrying capacity of the blood and tissues and organs do not get adequate oxygen and thus cannot develop and function normally. Thalassaemias are inherited as autosomal recessive disorders. If both the parents are carriers of the gene then there are 25% chances of baby being born as Thalassaemia Major (severe form of the disease), 50% carriers and 25% will be normal. Carrier persons remain asymptomatic and donot require any treatment but they should not marry a carrier but if already married or both the carrier persons want to marry then they should get genetic counseling before planning their family and should go for pre-natal diagnosis at 10-12 weeks of pregnancy. If the fetus is Thalassaemia Major then the couple has the option of medical termination of the pregnancy. So every boy and girl should undergo a blood test for HbA2 (HPLC) estimation and if it is between 3.5% to 9 % then the person is beta Thalassaemia carrier and should utilize this information at the time of his / her marriage.
Transfusion dependence has recently become an essential factor in classifying various phenotypes of B Thalassaemia. Transfusion dependent Thal. (TDT) are patients requiring lifelong regular blood transfusion therapy for survival such as patients with beta Thalassaemia Major or severe HbE/ B Thalassaemia. Non transfusion dependent (NTDT) patients donot require lifelong transfusion for survival such as beta Thalassaemia intermedia or mild-moderate HbE B Thal. patients. (Transfusion profile of patients in past 6 months — <6 RBC units denoting NTDT)
B Thalassaemia Major usually present after 6 months and by the age of 2 years most patients are diagnosed. Thal. intermedia present by 5-7 years or in some cases even later. Diagnosis is usually made on clinical findings and confirmed by various blood tests like CBC, PBF examination, HPLC (for quantitation of the Hb fractions). The molecular diagnosis is helpful in cases of uncertain diagnosis and for genetic counseling.
Main treatment options are :- a) Regular safe NAT tested Leucodepleted (prestorage filtration), Packed Red Cells (IAT Cross matched) with extend RBC matching and maintaining pre-transfusion Hb level of 10gms/dl and post transfusion Hb below 14 to 15gms/dl. b) Appropriate iron chelation therapy as advised to keep serum ferritin under 1000ng/ml c) MRI T2* for liver and cardiac iron concentration d) Immunization as advised e) Regular follow-up with multi-speciality approach (Cardiology, Endocrinology, Hepatology, Orthopedics, Radiology, Dentist, Gynaecologist for girl patients and Psychologist) with strict compliance.
New Drugs : Drugs that target ineffective erythropoiesis and anaemia so that RBC lifespan is increased, transfusion requirement is reduced, iron overload is reduced and Hb levels also improve : a) Luspatercept (ACE-536) for patients of 18 years or older, 1mg/kg by s/c injection b) Mitapirat (AG-348) 100mg orally twice daily is currently being evaluated in phase two 3 trials in both NTDT and TDT patients. Agents targeting the hepcidin or ferroportin pathways have also been evaluated.
Bone Marrow / Haematopoietic stem cell transplant – It is a curative treatment but has significant risks. In India Thalassaemia free survival (TFS) for lucarelli class I & class II patients was 78% at CMC Vellore. Gene Therapy — It works by putting functional copies of the abnormal gene into patients own blood stem cells. The RBCs are then able to make normal or near normal levels of Hb (FDA approved). Other types of gene therapy are being studied.
JKTWS-J&K Thalassaemia welfare society is doing a great job for the last 28 years for the welfare of these patients. The President JKTWS who works day and night for these patient care activities is the main force behind the society. The activities include regular blood donation camps, medical camps in which internationally renowned hematologist from Delhi come and examine these patients. Society also addresses various issues of the patients by discussing with GMC Jammu and hospital authorities and also with the Government of J&K UT and these efforts have been successful in improving various facilities at day care centre in SMGS Hospital Jammu. The Executive members of the society are equally involved in these activities and are committed to work for the welfare of these patients till there is a permanent cure for each and every patient. In Jammu 330 patients are registered with JKTWS. In Kashmir 27 patients are registered at GMC Srinagar under Paedriatic Haematologist.
(The author is Medical Advisor JKTWS & Former Prof. & Head Pathology Dept, GMC, Jammu)
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