Managment of Thalassemia

Management of Thalassemia

DR SYED MUHAMMAD ALIMS (TRAINEE DEPARTMENT OF

FACIOMAXILLARY KMDC)Under supervision of

Prof DR SYED MAHMOOD HAIDERHead OMFS DEPARTMENT

KARACHI MEDICAL AND DENTAL COLLEGE KARCHI [email protected]

THALASSEMIA

Word Thalassemia is derived from the Greek word Thalass ("sea") and -emia ("blood").

The Disease is very common in peoples living in Mediterranean geographical region, but found all over the world including Pakistan.

It is a autosomal, single gene recessive blood disease It is characterized by reduced or absent amounts of

hemoglobin (Cooley & Lee 1925; Rund & Rachmilewitz, 2005; Verma et al., 2011)

KINDS OF THALASSEMIA

There are two basic groups of thalassemia disorders:

α thalassemia β thalassemia.

ALPHA (α) THALASSEMIA

The α-thalassemia involve the genes HBA1 and HBA2, inherited in a Mendalian fashion.

There are two gene loci and so four alleles

It is also connected to the deletion of the chromosome 16.

α Thalassemia result in decreased alpha-globin production, therefore fewer alpha-globin chains are produced, resulting in an excess of β chains in adults and excess γ chains in newborns.

BETA (β)THALASSEMIA

Beta(β)thalassemia are due to mutations in the HBB gene on chromosome 11, inherited in an autosomal recessive fashion.

The severity of the Disease depends on the nature of the mutation.

Mutations are characterized as either βo or β

Thalassemia major :- No formation of β chains, the most severe form of β thalassemia.

Management before the Thalassemic Disease occur Management after the Thalassemic Disease occur

Management of Thalassemia

Control or stop consanguineous marriages among the carrier

Stop birth of Thalassemic child

Management before the Thalassemic Disease occur

Thalassemia is a inherited autosomal recessive blood disease

Population screening identification of carrier and genetic counseling are necessary for controlling the disease

Prenatal diagnosis can be done by relative rate of globin biosynthesis by fetoscopy and fetal blood sampling around 16 to18 week of intrauterine life or by analysis of foetal DNA by ultrasound guided chorionic villous biopsy at around 8-9 week of gestation or fetal aminocytes by aminocentesis if both parent are carriers

Antenatal diagnosis and genetic counseling

The following method are being used to managed and minimize the harmful effect

Bone marrow transplantation Neocyte Transfusion Genetic engineering Blood transfusion

Management after the Disease

Test of Thalassemia.

.A complete blood count (CBC) reveals anemia•Red blood cells will appear small and abnormally shaped when looked at under a microscope..•A test called hemoglobin electrophoresis shows the presence of an abnormal form of hemoglobin.A test called mutational analysis can help detect alpha thalassemia that cannot be seen with hemoglobin electrophoresis.

It is the most accurate and future plan of thalassemia control It is most expensive treatment option for permanent

treatment for thalassemia The principle of bone marrow transplantation are To destroy and prevent regeneration of defective stem cells Sufficient immune suppression for good engraftment of

normal marrow To infuse stem cells with normal gene for beta thalassemia The success ratio is 70 to 80 %

Bone marrow transplantation

Propper et al.,(1980) introduced the concept of transfusing Thalassemic children with young blood cell.

In conventional used unit of red blood cell has survival period is 60 days

The mean age of neocytes is 120 days they survives in the recipient is 90 days

Therefore reducing the amount of blood required and prolonging the interval between two transfusions.

Neocyte transfusion

This is the most advanced Technology. Insertion of normal gene in the stem cell recipient remain a

challenging goal of future therapy Somatic approach in which non germ cell are involved. Transgenic approach in which transfused gene can be

expressed gene and can be subsequent generation

Genetic engineering

Blood transfusion is mandatory for the thalassemic patient. It is not a permanent treatment for thalassemia but it extend

the life span Regular blood transfusion is the necessary for

survival

For all thalassemia major and thalassemia intermediate patient who can not maintain the blood up to 7gm

For those who show the evidence of growth retardation severe bony changes or hypersplenism

Blood transfusion

In low Transfusion regimen the Hb is maintained around 6 to 10gm

In Hyper transfusion Hb level 10 to 12 gm in Super transfusion Hb level is maintained 12 to 14 gm The popular method of transfusion regime of today is

hyper transfusion Such regimen permits normal growth and physical

activity ,suppress erythropoisis thus preventing skeletal changes and gastrointestinal iron absorption and also inhibits extramedullary hemopoisis there fore preventing splenomegaly .

Blood transfusion

Two factor contribute to iron overload in thalassemia child Enhanced GIT absorption of iron Transfusional hemosiderosis Transfusional overload leads to deposition of iron in heart

leading to cardiomayopathy and irregularity of heart beats, in the pancreas in the islet of langerhans leading to diabetes ,in the liver and spleen to hepatomegaly ,hepatic fibrosis and cirrhosis of liver and in pituitary glands leading to growth retardation delayed puberty in thyroid and parathyroid

Iron overload and chelation Therapy

Increase susceptibility to bacterial infection especially yersenia is seen with iron overload

Iron accumulation in the myocardium can lead to death either by involving the conducting tissues or causing intractable cardiac failure due to cardiomyopathy.

Iron overload

Desferrioxamine(DFO) is an ideal and only chelating agent of real value for the management of thalassemia to promote the excretion of iron

Given on the daily basis for optimum 5to 6 times per week, It is given subcutaneously over 6 to 8 hours using pump as infusion pump. The daily dose of deferal is about 30 to 70mg/kg and should be given according to need for the patient .

In general the goal is to keep the serum ferritin level below 1000 mg/ml

CHELATING AGENTS

Ascorbic acid deficiency causes increase insoluble iron in body

vitamin C help in conversion of hemosiderin into ferritin from which iron can be chelated.

Addition of vitamin C 100mg daily prior to DFO Therapy.

Role of viamin c

Febrile reaction It is found in 3 to 20 % of patient , due to leukocytes or

platelet antibodies against RBC antigens. Hemolytic transfusion reaction. Other reaction rarely seen which are uncertain

etiology and causes sudden development of hypertension convulsion, cerebral hemorrhage and edema after multiple transfusion

Transfusion transmitted disease like malaria ,syphilis hepatitis cytomegalovirus and HIV infection can occur

Complication of thalassemia

If the child is above 5 years with splenomegaly its splenectomy is indicated

With the advent of hyper and super transfusion therapy splenectomy is usually no needed in these patient because splenomegaly and hypersplenism have become a rarity

splenectomy

Thalassemia in Pakistan and Azad kashmir

Pakistan has a large population of more than 180 millionsThalassemia is a major health concern in Pakistan and is the most prevalent genetically transmitted blood disorder, with a carrier rate of 5-8% 5000 children in Pakistan is diagnosed with thalassemia every year Anonym (2012). Published: October 23. More than 100,000 thalassemia major children may be found in Pakistan.In Azad Kashmir it is 5%, there is only one blood bank in public sector which is insufficient for a large population, Gilaniet al.(2012)

Treatment and its expenditure

For optimum treatment of every thalassemic child will need frequent transfusions of screened packed red cells and regular iron chelating therapy. This will cost more than Rs.250000 per annum

In Azad Kashmir it is 5%, there is only one blood bank in public sector which is insufficient for a large population, Gilaniet al.(2012)

Jafri (2010) reported consanguineous marriages are one of reason to spread this disease and cause various consanguineous marriages are responsible of Craniofacial abnormalities, orofacial pigmentation. Naiduetal, (2010) reported that consanguineous marriages are common in muslim in India. (Hussain,(2000).Also reported that It is also true in Pakistan.

In Pakistan there are some communities where consanguineous marriages are very common like Persies, Khojas, Meomon and Aghakhanes, Genetically they are all alike they are of same colour, structure ,shape therefore it is predicted that occurrence of genetically inherited disease will be in great number.

Federal Govt,of Pakistan has passed a bill in National Assembly,2013 that screening of thalassemia test is compulsory before marriage Governor of Sindh in 2014 also passed an ordinance in this connection.