Thalassaemia

Presented ByPresented By

Dr. Md. Salahuddin ShahDr. Md. Salahuddin ShahAssistant Professor of HematologyAssistant Professor of Hematology

BSMMU, Shahbag,Dhaka.BSMMU, Shahbag,Dhaka.

Prevent thalassaemia & save the Nation

LAB ONE Thalassaemia Foundation

ThalassaemiaThalassaemia

Disorders of HaemoglobinDisorders of Haemoglobin

1. Thalassaemia1. Thalassaemia

2. Haemoglobinopathies2. Haemoglobinopathies

Demographics: ThalassemiaDemographics: Thalassemia

• Found most Found most frequently in the frequently in the Mediterranean, Mediterranean, Africa, Western and Africa, Western and Southeast Asia, Southeast Asia, India and BurmaIndia and Burma

• Distribution Distribution parallels that of parallels that of Plasmodium Plasmodium falciparumfalciparum

Incidence (carrier )

WORLD

Beta thalassemia trait 8% of population More than 100 milions carrier Haemoglobin E 53 milions

BANGLADESH

Beta thalassemia trait 4.1%

Haemoglobin E trait 6.1%

Combine Beta thalassemia & E trait 10.2%

GLOBAL ISSUESGLOBAL ISSUES

Beta Thalassaemia & Hb-E Beta Thalassaemia (Major)

Expected Beta thalassemia Major - 52,017

Expected HbE Beta thalassemia - 3,22, 137

Expected Beta thalassemia Major born per year – 1040

Expected HbE Beta thalassemia born per year – 6443

What is Thalassaemia ?What is Thalassaemia ? Thalassaemia is a group of Thalassaemia is a group of

inherited disorders of inherited disorders of hemoglobin synthesis hemoglobin synthesis characterized by a reduced or characterized by a reduced or absent output of one or more of absent output of one or more of the globin chains of adult the globin chains of adult hemoglobin .hemoglobin .

The name is derived from the The name is derived from the Greek words Thalasso = Sea" Greek words Thalasso = Sea" and "Hemia = Blood" in and "Hemia = Blood" in reference to anemia of the sea.reference to anemia of the sea.

Types of Thalassaemia :Types of Thalassaemia :

There are tThere are two basic groups of wo basic groups of thalassaemia.thalassaemia.

Alpha ( Alpha ( )Thalassaemia )Thalassaemia

Beta ( Beta ( )Thalassaemia )Thalassaemia

HaemoglobinopathiesHaemoglobinopathies

Haemoglobinopathies are Haemoglobinopathies are characterized by the production characterized by the production of structurally defective of structurally defective Haemoglobin due to Haemoglobin due to abnormalities in the formation of abnormalities in the formation of globin moiety of the molecule.globin moiety of the molecule.

Haemoglobin E trait

Haemoglobin E diseases

Heme portion of Heme portion of haemoglobinhaemoglobin

Globin portion of haemoglobinGlobin portion of haemoglobin

HaemoglobinHaemoglobin

Haemoglobin is a Haemoglobin is a conjugated protein.conjugated protein.Present within the RBCPresent within the RBC

Normal Human Normal Human HaemoglobinsHaemoglobinsHaemoglobiHaemoglobi

nnStructural Structural formulaformula

AdultAdult Hb-AHb-A 2 2 2 2 97%97%

Hb-AHb-A22 2 2 2 2 1.5-1.5-

3.2%3.2%

FetalFetal Hb-FHb-F 2 2 2 2 0.5-0.5-

1%1%

Hb-Bart’sHb-Bart’s 44

EmbryonicEmbryonic Hb-Gower Hb-Gower 11

2 2 22

Hb-Gower Hb-Gower 22

2 2 22

Hb-Hb-PortlandPortland

2 2 22

The common abnormal The common abnormal haemoglobinshaemoglobins

HaemoglobinHaemoglobin Structural formulaStructural formula

Hb-SHb-S 2 2 2 2 6 glu 6 glu val val

Hb-CHb-C 2 2 2 2 6 glu 6 glu lys lys

Hb-EHb-E 2 2 2 2 26 glu 26 glu lys lys

Hb-D PunjabHb-D Punjab 2 2 2 2 121 glu 121 glu gln gln

Normal Normal RBCRBC

Haemoglobin in Haemoglobin in RBCRBC

Origin & Development of Red Origin & Development of Red Blood CellBlood Cell

←←Bone Marrow Sites & Bone Marrow Sites & FunctionsFunctions

Bone Bone MarrowMarrow

↓↓

ChromosomesChromosomes

Types of Beta Thalassaemia Types of Beta Thalassaemia ::

There are 3 types of Beta thalassaemia :There are 3 types of Beta thalassaemia :

1.1. Thalassaemia MinorThalassaemia Minor

2.2. Thalassaemia IntermediateThalassaemia Intermediate

3.3. Thalassaemia MajorThalassaemia Major

Signs & SymptomsSigns & Symptoms Thalassaemia Minor : Usually no signs or symptoms except for a mild anemia.

Thalassaemia Major :Thalassaemia Major :1. Paleness, Jaundice or yellow coloured skin.2. Growth retardation.3. Bony abnormalities specially of the facial bones.4. Enlarged spleen and liver.

Laboratory DiagnosisLaboratory Diagnosis Thalassemia minor:Thalassemia minor: Haemoglobin : Haemoglobin level is Haemoglobin : Haemoglobin level is

usually normal or mildly reduced. usually normal or mildly reduced. Peripheral blood film : Hypochromia Peripheral blood film : Hypochromia

and Microcytosis (similar to Iron and Microcytosis (similar to Iron Deficiency Anemia).Deficiency Anemia).

MCV< 75 fl, MCV< 75 fl, RDW < 14%.RDW < 14%. Haemoglobin electrophoresisHaemoglobin electrophoresis HPLCHPLC DNA analysisDNA analysis

Thalassemia major :Thalassemia major : Blood film : Blood film :

RBC : profound microcytic with RBC : profound microcytic with extreme extreme hypochromia, tear hypochromia, tear drop, target drop, target cells and nucleated cells and nucleated RBCs.RBCs.

Hemoglobin may be very low at 3-4 g/dl.Hemoglobin may be very low at 3-4 g/dl. Haemoglobin ElectrophoresisHaemoglobin Electrophoresis

Laboratory Diagnosis (Cont)Laboratory Diagnosis (Cont)

Haemoglobin Haemoglobin electrophoresiselectrophoresis

AA

FF

SS

CC

Course and treatment of Course and treatment of thalassaemiathalassaemiaUntreated Untreated

thalassemia thalassemia Major Major : :

Death in first or second Death in first or second

decade of life decade of life

IntermediaIntermedia: variable life span: variable life span

Minor/MinimaMinor/Minima: Normal life span: Normal life span

Thalassaemia major life Thalassaemia major life expectancyexpectancy

Without regular transfusionWithout regular transfusion Less than Less than 10 years10 years

With regular transfusion and With regular transfusion and no/poor iron chelationno/poor iron chelation Less than Less than 25 years25 years

With regular transfusion and With regular transfusion and good iron chelationgood iron chelation ??40 years, ?longer????40 years, ?longer??

Management and treatment

Thalassemia minor (trait) :

No need for any treatment, since the carriers are usually symptomless.

Thalassemia major:

The severe life-threatening anemia, requires regular life long blood transfusion, to compensate for damaged red blood cells.

““Regular transfusions”Regular transfusions”

““Regular transfusions”Regular transfusions” Start within 1Start within 1stst year of life year of life

Usually every 4-6 weeks – Usually every 4-6 weeks – THROUGHOUT LIFETHROUGHOUT LIFE

maintain Hb 9-10.5g/dl

Regular blood transfusionRegular blood transfusion Safe Blood transfusionSafe Blood transfusion

Screening test for donarScreening test for donarMPMPVDRLVDRLHIVHIVHCVHCVHBsAgHBsAg

Full blood group, genotype should be obtained Full blood group, genotype should be obtained before the first transfusion.before the first transfusion.

Pre & post trasfusion Haemoglobin level.Pre & post trasfusion Haemoglobin level. Assessment of body iron statusAssessment of body iron status

by Serum ferritinby Serum ferritin Hepatic iron concentrationHepatic iron concentration

Children : liver biopsy Children : liver biopsy annually or at least every 2 – 3 years.annually or at least every 2 – 3 years.

““Regular transfusions” (cont)Regular transfusions” (cont)

■ ■ Regular assessment of potential complications:Regular assessment of potential complications:

Growth charts, Growth charts, Checks for diabetes, Checks for diabetes, Done density scans, Done density scans, Cardiac and liver MRI scans.Cardiac and liver MRI scans.

■■ Chronic iron overload Chronic iron overload ■■ Infection through blood transfusions Infection through blood transfusions ■■ Viral hepatitis, HIV, HCV, Malaria, Syphilis. Viral hepatitis, HIV, HCV, Malaria, Syphilis. ■ ■ Other blood borne infectionsOther blood borne infections

■ ■ COST ???COST ???

Transfusion services in Transfusion services in DhakaDhakaScreening TestsScreening Tests HospitalHospital RateRate

MPMP

VDRLVDRL

HCVHCV

HBsAgHBsAg

HIVHIV

Others :Others :

GroupingGrouping

Cross matchingCross matching

BSMMUBSMMU Tk. 600/-Tk. 600/-

Red CrescentRed Crescent Tk. 760/-Tk. 760/-

BIRDEMBIRDEM Tk. 1000/-Tk. 1000/-

QuantumQuantum Tk. 600/-Tk. 600/-

Apolo / SquareApolo / Square Tk. 2500/-Tk. 2500/-

Other General Clinic Other General Clinic & Hospitals& Hospitals(Screening tests : Done (Screening tests : Done according to the desire according to the desire of the patient)of the patient)

Tk. 50-100/-Tk. 50-100/-

Tk. 150-200/-Tk. 150-200/-

Tk. 300-600/-Tk. 300-600/-

Tk. 200-300/-Tk. 200-300/-

Tk. 300-600/-Tk. 300-600/-

Lab One Thalassaemia Lab One Thalassaemia FoundationFoundation

All Screening tests +All Screening tests +

Day care service (Blood transfusion) +Day care service (Blood transfusion) +

Grouping & Cross matching +Grouping & Cross matching +

Consultation (By Haematologist) =Consultation (By Haematologist) =

Tk. 800/- only.Tk. 800/- only.

(Only for thalassaemic patients)(Only for thalassaemic patients)In case of donation (blood bag & test In case of donation (blood bag & test

reagents) reagents)

we can reduce the charges by 50%. we can reduce the charges by 50%.

Complications of iron Complications of iron overloadoverload

Multi-organ failureMulti-organ failure Endocrine organsEndocrine organs

Growth failureGrowth failure DiabetesDiabetes Thyroid failureThyroid failure Gonadal failure - infertilityGonadal failure - infertility

CardiacCardiac LiverLiver

IRON CHELATIONIRON CHELATIONIRON CHELATIONIRON CHELATION

ChelatorChelator

PrescriptionPrescription

Follow upFollow up

ChelatorChelator

PrescriptionPrescription

Follow upFollow up

STANDARD TREATMENTSTANDARD TREATMENT

Desferrioxamine (Desferal®)Desferrioxamine (Desferal®)20-60 mg/kg/day20-60 mg/kg/day10% solution10% solution8-12 hours s.c. slow infusion8-12 hours s.c. slow infusionportable pumpportable pump7 days a week7 days a week

STANDARD TREATMENTSTANDARD TREATMENT

Desferrioxamine (Desferal®)Desferrioxamine (Desferal®)20-60 mg/kg/day20-60 mg/kg/day10% solution10% solution8-12 hours s.c. slow infusion8-12 hours s.c. slow infusionportable pumpportable pump7 days a week7 days a week

Management of iron chelating Management of iron chelating therapytherapy




WHEN TO START CHELATIONWHEN TO START CHELATION

transferrin saturation at 100%transferrin saturation at 100%10-20 units transfused 10-20 units transfused serum ferritin > 1000 serum ferritin > 1000 g/Lg/LLiver Iron Concentration > 1 mg/g Liver Iron Concentration > 1 mg/g

w.w.w.w.

WHEN TO START CHELATIONWHEN TO START CHELATION

transferrin saturation at 100%transferrin saturation at 100%10-20 units transfused 10-20 units transfused serum ferritin > 1000 serum ferritin > 1000 g/Lg/LLiver Iron Concentration > 1 mg/g Liver Iron Concentration > 1 mg/g

w.w.w.w.

Iron ChelationIron ChelationIron ChelationIron Chelation

SECOND LINE TREATMENTSECOND LINE TREATMENT

Deferiprone (Ferriprox®)Deferiprone (Ferriprox®)

50-100 mg/kg/day orally50-100 mg/kg/day orally

three times a daythree times a day

SECOND LINE TREATMENTSECOND LINE TREATMENT

Deferiprone (Ferriprox®)Deferiprone (Ferriprox®)

50-100 mg/kg/day orally50-100 mg/kg/day orally

three times a daythree times a day



-EU Approval Aug 06

-Once daily orally (as a drink)

-Approved for age 6 and above

-(Expensive!)

New Developments in Iron Chelation

Asunra Asunra (Deferasirox) (Deferasirox)

Iron OverloadIron Overload

ThalessemiaThalessemia Myelodysplastic Myelodysplastic SyndromesSyndromes

Sickle CellSickle Cell

ICL670ICL670Setting the Stage for a Revolution In Iron ChelationSetting the Stage for a Revolution In Iron Chelation

Iron Chelation Therapy

Iron Overload from Iron Overload from TransfusionsTransfusions

With repeated blood transfusion, With repeated blood transfusion,

iron accumulatesiron accumulates Iron overload can lead to early Iron overload can lead to early

mortalitymortality1,21,2

Current therapy using IV pump is Current therapy using IV pump is

unpleasant, life altering and unpleasant, life altering and

dramatically reduces compliancedramatically reduces compliance DesferalDesferal®® (deferoxamine) (deferoxamine) Subcutaneous slow infusion 5-7 Subcutaneous slow infusion 5-7

nights/weeknights/week Infusion-site reactions and painInfusion-site reactions and pain

Asunra (deferasirox):Asunra (deferasirox):A Novel Oral Iron ChelatorA Novel Oral Iron Chelator

Selected from more than Selected from more than

700 compounds tested700 compounds tested Tridentate* iron chelatorTridentate* iron chelator

An oral, dispersible tabletAn oral, dispersible tablet Administered once dailyAdministered once daily Highly specific for ironHighly specific for iron

Chelated iron excreted Chelated iron excreted

mainly in feces (<10% in mainly in feces (<10% in

urine)urine)

Lv`¨ Lv`¨ mvgMÖmvgMÖxi bvg xi bvg

AwaK †jŠnhy³ Lvevi AwaK †jŠnhy³ Lvevi (Iron rich diet)(Iron rich diet)

Kg †jŠn hy³ Lvevi Kg †jŠn hy³ Lvevi (Iron poor diet)(Iron poor diet)

gvsm I gvsm I gvsmRvgvsmRvZxq Zxq Lvevi Lvevi

Mi“i gvsm, Lvkxi Mi“i gvsm, Lvkxi gvsm, KwjRv, wW‡gi gvsm, KwjRv, wW‡gi Kzmyg, Bwjk, ˆK, Kzmyg, Bwjk, ˆK, wPswo, wPZj I †QvU wPswo, wPZj I †QvU gv‡Qi ïUwK| gv‡Qi ïUwK|

i“B , KvZj, cvsMvm, i“B , KvZj, cvsMvm, †evqvj, gv¸i , micywU I †evqvj, gv¸i , micywU I cywU gvQ| cywU gvQ|

kvK kvK mewRmewR

KPz kvK, jvjkvK, KPz kvK, jvjkvK, cvjskvK, cyuBkvK, cvjskvK, cyuBkvK, dzjKwc, cyw`bv cvZv , dzjKwc, cyw`bv cvZv , a‡b cvZv, wmg, eiewU a‡b cvZv, wmg, eiewU gUiïwU, KvK‡ivj, gUiïwU, KvK‡ivj, KvuPv‡cu‡c, mvRbv| KvuPv‡cu‡c, mvRbv|

evuavKwc, wgwóAvjy , evuavKwc, wgwóAvjy , Kijv, kkv, wgwó, Kijv, kkv, wgwó, Kzgov, †pom, †e¸b, Kzgov, †pom, †e¸b, g~jv, kvjMg, Av‡cj , †ej g~jv, kvjMg, Av‡cj , †ej , Rvgi“j, AvZv, , Rvgi“j, AvZv, AvgjwK , KvMwR‡jey| AvgjwK , KvMwR‡jey|

dj dj Avbvim, †e`vbv, Avbvim, †e`vbv, kwidv, †LRyi, ZigyR| kwidv, †LRyi, ZigyR|

cvKv Avg , wjPz, cvKv Avg , wjPz, †cqviv, Kjv, cvKv †cqviv, Kjv, cvKv †cu‡c, Kgjv‡jey, Av‡cj, †cu‡c, Kgjv‡jey, Av‡cj, †ej, Rvgi“j, AvZv, †ej, Rvgi“j, AvZv, AvgjwK| AvgjwK|

Lv`¨ kl¨ Lv`¨ kl¨ Ges Zv Ges Zv †_‡K †_‡K ‰Zwi ‰Zwi Lvevi Lvevi

ˆL, wkï Lv`¨ †hLv‡b ˆL, wkï Lv`¨ †hLv‡b †jŠn mshy³ Kiv Av‡Q †jŠn mshy³ Kiv Av‡Q †hgb (†hgb (cerelaccerelac), KvD(), KvD(cowcow) ) Ges †MU(Ges †MU(gategate) BZ¨vw` ) BZ¨vw`

Pvj, gq`v|Pvj, gq`v|

Wvj Wvj ‡‡Qvjv, †Qvjvi Wvj| Qvjv, †Qvjvi Wvj| gmyi Wvj| gmyi Wvj|

wewea wewea ¸o, ev`vg, Pxbvev`vg, ¸o, ev`vg, Pxbvev`vg, wKmwgm, wZj, cvb, wKmwgm, wZj, cvb, a‡b, mwilv| a‡b, mwilv|

gay, `ya I `y»RvZ gay, `ya I `y»RvZ Lvevi h_v: `B, Qvbv, Lvevi h_v: `B, Qvbv, cwbi, im‡Mvj v BZ¨vw`| cwbi, im‡Mvj v BZ¨vw`|

_¨vjvwmwgqv †ivMxi Lv`¨_¨vjvwmwgqv †ivMxi Lv`¨

• F-Globin Induction Agent HydreaAzacytidine Sodium phenylbutyrate Epo

• Bone Marrow transplantationNo convincing data Expensive

• Gene Therapy Inserting healthy genes into stem cells and transplanting

Splenectomy

Indications :

• Trasfusion requirements increased --------

50% in 6 months

• RBCs per year >250ml/kg

• Severe leukopenia or thrombocytopenia

• Massive splenomegaly

• Blood donation

• Motivate others to donate blood. • Spread this message to others. • Donate something from your hard earned money to the society.

WHAT WE CAN DO?

Prevention of thalassaemia?Prevention of thalassaemia?

Awareness.Awareness. Screening tests.Screening tests. Genetic counseling.Genetic counseling. Prenatal diagnosis and therapeutic Prenatal diagnosis and therapeutic

abortion. abortion.

PRENATAL TESTINGPRENATAL TESTING

AmniocentesisAmniocentesis

Chorionic biopsyChorionic biopsy

INVASIVE MODES OF SAMPLE INVASIVE MODES OF SAMPLE COLLECTIONCOLLECTION

AmniocentesisAmniocentesis Around the 16Around the 16thth week of gestation week of gestation

Chorionic villus samplingChorionic villus sampling Before 10 week of pregnancyBefore 10 week of pregnancy

Foetal blood samplingFoetal blood sampling At about 18-20 weeks of pregnancyAt about 18-20 weeks of pregnancy

PRIMARY TARGET COUPLE

One thalassaemic baby The families of the patients & carriers

Carrier- carrier identify

CONCLUSION & RECOMMENDATIONS

☺To design, implement, reinforce comprehensive national and integrated program ☺ Surveillance, dissemination of information, awareness raising screening program

☺ Intensify training health professionals

CONCLUSION & RECOMMENDATIONS- CONT

☺ Develop and strengthen medical service☺ Promote community education☺ International cooperation☺ Basic and applied research on thalassemia ☺ To consider world health day on thalassemia the near future

AIM and OBJECTIVES ofAIM and OBJECTIVES of LAB ONE Thalassaemia LAB ONE Thalassaemia

FoundationFoundation To establish an integrated To establish an integrated

thalassaemia hospital.thalassaemia hospital. To develop facilities for safe blood To develop facilities for safe blood

transfusion.transfusion. To organize a thalassaemia donor To organize a thalassaemia donor

club.club. To create facilities for prenatal To create facilities for prenatal

diagnosis and DNA analysis.diagnosis and DNA analysis. To make awareness among To make awareness among

populations about thalassaemia.populations about thalassaemia.

We have taken One year action plan :We have taken One year action plan :

Thalassaemia screening Thalassaemia screening programme.programme.

Exchange views & knowledges Exchange views & knowledges among among others thalassaemia foundation others thalassaemia foundation through through our website & CME programs. our website & CME programs.

Documents

Thalassaemia