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ß Thalassemia:an Overview

by Abdullatif Husseini



W hat is thalassemia?Thalassemia is a group of inherited

disorders of hemoglobin synthesischaracterized by a reduced or absentoutput of one or more of the globin chainsof adult hemoglobin .The name is derived from the Greek

words Thalasso = Sea" and "Hemia =Blood" in reference to anemia of the sea.



Alpha ( E ) thalassemia

I t appears when a person does notproduce enough alpha chains forhemoglobin.

I t is mainly prevalent in the Africa, theMiddle East , I ndia, and occasionally inMediterranean region countries.



B eta (ß) thalassemiaI t appears when a person does not produce

enough beta chains for hemoglobin.

I t is mainly prevalent in the Mediterranean

region countries , such as Greece, Cyprus,I taly, Palestine and Lebanon.



Types of ThalassemiaE thalassemia: There are four typescategorized according to the severity of their effects on persons with thalassemia.

ß thalassemia: There are 3 typescategorized according to severity:

Thalassemia minorThalassemia intermediaThalassemia major



G enetics of ß thalassemia

Monogenic disorder: a single gene disorderß thalassemia result from over 150

mutations of the ß globin genes that resultin the absence or a reduction of the ß globinchains



C hromosomes

Source: Thalassemia.com



Transmission of ß thalassemia

I f a carrier (thalassemia minor)marries a non-carrier, on averagehalf of their children will be carriers,

but none will develop thalassemiamajor.



Transmission ß of thalassemia - C ont

However if two carriers marry, ineach pregnancy there is a 25%chance of a non-carrier child, a 50%chance of a carrier child(thalassemia minor), and a 25%chance of a child with thalassemiamajor.



An example of inheritance - C ont:marriage between two carriers

Source: Emirates Thalassemia Society



Types of ß thalassemiaThalassemia Minor (Trait) .

This can also be called (carrier state),meaning that the person carries thegenetic trait for thalassemia.

Such people usually practice normallife, but may suffer from a mild form of anemia.



Types of ß thalassemia- C ont

Thalassemia Intermedia .

Caused by the reduced availability of beta chains in hemoglobin and canlead to moderate to severe anemia

and an array of complicationsincluding bone deformities andsplenomegaly.



Types of ß thalassemia- C ont

Thalassemia Major (C ooley's Anemia) .

Caused by the unavailability of betachains in hemoglobin leading to a verysevere and fatal if left untreated anemia.

I t requires regular blood transfusionsleading to iron-overload which is treatedwith chelation therapy to prevent deathfrom organ failure.



ß thalassemia and malariaThalassemic RBCs offers protectionagainst severe malaria caused by

Plasmodium falciparum .The effect is associated with reducedparasite multiplication within RBCs.

Among the contributing factors may bethe variable persistence of hemoglobin F,which is relatively resistant to digestionby malarial hemoglobinases.



S igns and symptomsThalassemia carriers (trait):

Usually no signs or symptoms areapparent, except for a mild anemia.Carriers are usually initially detectedthrough screening, or when performingroutine CBC (complete blood count).Later it can be confirmed usinghemoglobin electrophoresis.



S igns and symptoms- C ont

Thalassemia major:

Signs such as paleness and growthretardation, are readily detectablesince the first year of life. Those are

mainly due to severe anemia. Laterbone deformities and hepato-splenomegaly develops .



L aboratory diagnosisThalassemia minor:

-Blood smear shows hypochromia andmicrocytosis (similar to I ron DeficiencyAnemia).-Blood indices: MCV< 75 fl, Hb usually>

10, Hematocrit> 30%, RDW < 14%.-Hemoglobin A2 often elevated > 3%,sometimes reaching 7-8%.



L aboratory diagnosis- C ont

Thalassemia major:

-Blood smear shows profoundmicrocytic anemia, with extremehypochromia, tear drop, target

cells and nucleated RBCs.-Hemoglobin may be very low at3-4 g/dl.



Blood picture of a ß thalassemiamajor patient

Source: Cooley¶s Anemia Foundation



Prenatal diagnosisEarly prenatal diagnosis can be done

using first fetal blood sampling, andlater chorion villus biopsy and directanalysis of the globin genes.

The error rate in experiencedcenters is now well under 1%.



Management and treatment Thalassemia minor (trait) :

No need for any treatment, since thecarriers are usually symptomless.Thalassemia major:

The severe life-threatening anemia,requires regular life long bloodtransfusion, to compensate for damaged

red blood cells.



Management and treatment- C ont Thalassemia Major:

The continuous blood transfusion willeventually lead to iron overload, whichmust be treated with chelation therapy to

avoid organ failure.



Source: Cooley¶s Anemia Foundation



Management and treatment- C ont Thalassemia Major -Continued:Other novel treatments like bone-marrowtransplantation are very costly.New treatments includes the use of oralchelators, to replace the chelation treatmentusing Desferal delivered by infusion underthe skin through a battery-operated pump.Gene therapy is also an option still researched



Prevention effortsPre marital screening to make sure thatthe couple are not both carriers.

Provision of counseling and healtheducation for the thalassemics, theirfamilies and the public .

Provision of prenatal testing forthalassemia.Reduction of marriages betweenrelatives.



Thalassemia and migrantsCountries with migrants coming fromareas with high prevalence of thalassemiasuch as the Mediterranean region, shouldbe aware of this problem.Families with thalassemia carriers may

have increased number of cases includingthalassemia major due to intermarriagesbetween relatives, especially in closedcommunities



Thalassemia and migrants - C ont The following recommendations areadvised:

1- Training physicians and medical staff on thalassemia diagnosis and treatment.2- Provision of screening and counseling

services for those exposed.3- Provision of appropriate health careand management for thalassemiapatients .



Thalassemia and migrants - C ont 4- Overcoming the communication

problems, including languagebarrier through utilizing translatorsand nurse practitioners.

5- Community educationalprograms, involving communityleaders and providing social support.



Problems commonly faced by thalassemiamajor patients in developing countries

Reduced availability of blood fortransfusion.Reduced availability of Desferalpumps, less than third of the patientshave access to pumps.High cost of treatment.



Problems commonly faced by thalassemiamajor patients in developing countries - C ont

Limited services that blood banksare able to give.Unavailability of counseling services.Lack of experience and appropriatetraining among the health providersto handle thalassemia cases.



Acknowledgement AcknowledgementI would Like to thank Dr. Hisham Darwish & Dr. Bashar al-Karmi from

Thalassemia Patients¶ Friends S ociety (TPF S )-Palestine

F or the valuable information they provided.I would also like to express my sincere thanks for the

Palestinian American Research Center (PARC) for providing me with a grant which allowed me to conductresearch at the University of Pittsburgh, where I started

preparing this lecture.

beta+thalassemia (1)

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