Thalassemia “Bad Blood By Mutations”

Dr Rashid Merchant

World Hepatitis Day

5

6

60 Million

112 Million

72 Million

• MAHARASHTRA• GUJARAT• MADHYA

PRADESH

SindhisBhanushalisBhatiasKhojasBhorasMarathasLuwanasKucchis

Communities:

screen forthalassemia

New births of beta-thalassemia major can be prevented

do it the right way

The screening test needs to done only once in a person’s life

but done the right way

urgent need to identify all carriers

screen forthalassemia

Lab Investigations - Carriers

Hb < 10-11gmsRBC > 5 millionMCV < 76MCH < 26Mentzer’s Index <13 (MCV/RBC)RDW NormalPBS - micro, hypo Suspect Thal. minor/IDAHb Electrophoresis (HPLC) HbA2 > 3.5% -------Thal. Minor

You could be a Thalassaemia Minor

There is nothing wrong in being a Thalassaemia Minor

Picture of thal minor

There is everything wrong in not knowing that you are a

Thalassaemia Minor

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DemographyWorldwide:

5 million people – symptomatic clinically240 million carriers of β -thalassemia gene

India:30 million carriers of β-thalassemia thalassemia

gene10,000 cases added every year

Carrier rate:4% carrier rate in India

One thalassemic is born every hour

Let’s look at Cyprus……

Can we replicate Cyprus model

Cyprus has highest Thal. prevalence

No child with Thal. maj born in last 10 yrs

Prenatal: awareness/ counselling/ testing

Couple getting married needs church license for marriage, which is given after testing for Thalassemia

Transfusion Transmitted Infections

HIV Screening antibodies /Confirmed PCRHBVHCVCMVMalariaSyphilisYersiniaBacteria

Heart is the lethal target organ in ThalassemiaCardiac complications are >75% cause of

mortality Adequate iron chelation is mandatory to

prevent cardiac diseaseQuantitative MRI T2* best evaluates cardiac

iron overload

No Bone Deserves A Break

Cardiac : Major cause of mortality

Bone : Major cause of morbidity (Osteopathy) (pain/fractures/deformities)

Incidence 80-90% (>15 yrs)

2 - D ECHO

OUR EXPERIENCE IN CARDIAC/LIVER IRON QUANTIFICATION

MRI T2* Cardiac/Liver Iron in ThalassemiaT2* - 1.5 Tesla, SEIMENS machine,Thal. Tools software

CENTRE : JHANKARIA CLINIC,

PIRAMAL DIAGNOSTICS , MUMBAI

Rashid MerchantAditi Joshi Pradeep KrishnanBhavin Jhankaria

MRI IS ABLE TO DETECT SINGLE ORGAN IRON IRON LOAD

TO TAILOR CHELATION TREATMENT ON SINGLE ORGAN DAMAGE

HYPOPHISYS

HEART LIVER

PANCREAS

Normal Iron overloading NormalIron overloading

Normal Iron overloading NormalIron overloading

Hepatic Evaluation METAVIR STAGING

FIBROSIS

•F0 – no fibrosis•F1 – portal fibrosis without septa•F2 – portal fibrosis with few septa•F3 – numerous septa without cirrhosis•F4 – cirrhosis

ACTIVITY•A0 – no activity•A1 – mild activity•A2 – moderate activity•A3 – severe activity

TRANSIENT ELASTOGRAPHY(Our Experience)

Ultrasound based technique Measures the liver stiffness Measures the propagation velocity of

SHEAR WAVES

Harder tissueFaster

propagationHigher velocity

FIBROSCAN

Fibroscan

Discussion

Liver biopsy is the gold standard for fibrosis staging

Not feasible to monitor progression & treatment response

Liver elastography is a noninvasive alternative

It is shown to correlate with liver enzymes

Variable correlation with S. Ferritin & MRI T2* liver

No Bone Deserves A Break

Cardiac : Major cause of mortality

Bone : Major cause of morbidity (Osteopathy) (pain/fractures/deformities)

Incidence 80-90% (>15 yrs)

Osteoporosis TreatmentVitamin D 1000 IU/day

Calcium 1000-1500 mg/day

Bisphosphonates: osteoclastic activity

Hormone replacement treatment

rPTH (Forteo): osteoblastic activity

Calcitonin nasal spray (inhibits osteoclasts)

TreatmentCalcitonin nasal spray (inhibits osteoclasts)

Duration = 6 weeks

200 IU / day

Especially vertebral fractures, severe bone pains

Chelator MetalChelator

Toxic

Excretion

Metal

What is chelation therapy?

Overview of iron chelators

PropertyDeferoxamine (DFO)

Deferiprone (DFP) Deferasirox

Usual dose 25–60 mg/kg/day 75 mg/kg/day 20–30 mg/kg/day

Route s.c., i.v.8–12 h, 5 days/week

p.o.3 times daily

p.o.once daily

Half-life 20–30 min 3–4 h 8–16 h

Excretion Urinary, faecal Urinary Faecal

Adverse effects

Local reactions, ophthalmological, auditory, growth retardation, allergic

GI disturbances, agranulocytosis/ neutropenia, arthralgia, elevated liver enzymes

GI disturbances, rash, mild non-progressive creatinine increase, ophthalmological, auditory, elevated liver enzymes

Status Licensed Not licensed in USA or Canada

Licensed

Approved indications

Treatment of chronic iron overload due to transfusion-dependent anaemias

Thalassaemia major Treatment of chronic iron overload due to frequent blood transfusions

GI = gastrointestinal; i.v. = intravenous; p.o. = per orum; s.c. = subcutaneous.

Desferal is effective

Compliance is the issue

By 15 years By 50 years

250 units PCV 2000 units PCV

4000 inj of DFO 15,000 inj of DFO

Rs 16.5 lacs expenses (DFO &

L1)

Rs 90 lacs expenses (DFO & L1)

40,000 hours needle stuck in

1.5 lacs hours needle stuck in

DEFERIPRONE (L1)India - first country to launch in 1994.

Available in 40 countries.

Used in more than 7500 patients.

More powerful cardiac iron chelator than

DFO

DFO + L1 : best combination for chelation

ICL 670

How to take DFX ?STEP 1:

DROP the tablet(s) into a glass of orange juice, apple juice, or water (100 ml or 200 ml)

How to take DFX ?STEP 2:

STIR until the tablet(s) are completely dissolved

The liquid in the glass will look cloudy

The cloudy liquid means the medicine is mixed in

WHAT & HOW WE MONITOR??

TYPE OF TEST ORGAN FREQUENCYECG/ 2D ECHO HEART ANNUALY

MRI T2* LIVER/ HEART ANNUALY

SONOGRAPHY ABDOMEN/PELVIS ANNUALY

XRAY CHEST ANNUALY

DEXA(BMD) BONE ANNUALY

(Ca,P,Alk-Poshphatase), Blood Sugar

BLOOD ANNUALY

VIRAL MARKERS HBV/HCV/HIV ANNUALY

RBC ANTIBODIES DCT/ICT ANNUALY

HORMONAL ANALYSIS

THYROID (T3+T4+TSH), IGF1

FSH/LH& ER/TESTOSTERONE

ANNUALY

BUN/Sr. Cr, URINE,LFT

BLOOD 1-3 MONTHLY

SERUM FERRITIN BLOOD 3 MONTHLY

New Thalassemia EraDr. Rashid Merchant

Pediatrician• Former Dean & Prof. Pediatrics

B.J. Wadia Child Hospital Mumbai• Presently Consultant Pediatrician

Nanavati Hospital Mumbai

Hydroxyurea(Hu) TherapyHu is hydroxamic acid compoundHu inhibits ribonucleotide reductaseHu stimulates Y chain synthesis(B gene)Increased Fetal HbUsed in Rx - Sickle / Hb-pathiesCytodrox(Cipla) 500mg/caps @ 10-20mg/kg/dayEffective minimal S/E. Safe for long term.S/E:Anemia, Thrombocytopenia, Neutropenia.

Stem Cell TherapyDr. Rashid Merchant

Stem cell is a single cell that can give rise to progeny (progenitor

cells) that can differentiate into

specialized cells of various tissues. In other words,

it is origin of life.

Persevere through the difficult patches and better times are sure to come

some time.