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.
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