Dr. rashid merchant presentation new era for thalassemia

1. Thalassemia
“Bad Blood By Mutations”
Dr Rashid Merchant
World Hepatitis Day

5. 5

6. 6

7. 60
Million
112
Million
72
Million
• MAHARASHTRA
• GUJARAT
• MADHYA PRADESH

8. Sindhis
Bhanushalis
Bhatias
Khojas
Bhoras
Marathas
Luwanas
Kucchis
Communities:

10. screen for
thalassemia
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 for
thalassemia

11. Lab Investigations - Carriers
Hb < 10-11gms
RBC > 5 million
MCV < 76
MCH < 26
Mentzer’s Index <13 (MCV/RBC)
RDW Normal
PBS - micro, hypo
Suspect Thal. minor/IDA
Hb Electrophoresis (HPLC)
HbA2 > 3.5% -------Thal. Minor

12. You could be a Thalassaemia Minor
There is nothing
wrong in being a
Thalassaemia Minor

13. Picture of thal minor

14. There is everything wrong in not
knowing that you are a
Thalassaemia Minor

16. 16
Demography
Worldwide:
5 million people – symptomatic clinically
240 million carriers of β -thalassemia gene
India:
30 million carriers of β-thalassemia thalassemia gene
10,000 cases added every year
Carrier rate:
4% carrier rate in India
One thalassemic is born every hour

17. Let’s look at Cyprus……

18. 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

20. Transfusion Transmitted Infections
HIV Screening antibodies /Confirmed PCR
HBV
HCV
CMV
Malaria
Syphilis
Yersinia
Bacteria

22. Heart is the lethal target organ in Thalassemia
Cardiac complications are >75% cause of
mortality
Adequate iron chelation is mandatory to
prevent cardiac disease
Quantitative MRI T2* best evaluates cardiac
iron overload

23. No Bone Deserves A Break
Cardiac : Major cause of mortality
Bone : Major cause of morbidity
(Osteopathy) (pain/fractures/deformities)
Incidence 80-90% (>15 yrs)

24. 2 - D ECHO

25. OUR EXPERIENCE IN CARDIAC/LIVER IRON QUANTIFICATION
MRI T2* Cardiac/Liver Iron in Thalassemia
T2* - 1.5 Tesla,
SEIMENS machine,Thal. Tools software
CENTRE : JHANKARIA CLINIC,
PIRAMAL DIAGNOSTICS , MUMBAI
Rashid Merchant
Aditi Joshi
Pradeep Krishnan
Bhavin Jhankaria

27. 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

28. 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

30. TRANSIENT ELASTOGRAPHY
(Our Experience)
Ultrasound based technique
Measures the liver stiffness
Measures the propagation velocity of SHEAR WAVES
Harder
tissue
Faster
propagation
Higher
velocity

31. FIBROS
CAN
Fibroscan

32. 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

33. No Bone Deserves A Break
Cardiac : Major cause of mortality
Bone : Major cause of morbidity
(Osteopathy) (pain/fractures/deformities)
Incidence 80-90% (>15 yrs)

39. Osteoporosis Treatment
Vitamin D 1000 IU/day
Calcium 1000-1500 mg/day
Bisphosphonates:  osteoclastic activity
Hormone replacement treatment
rPTH (Forteo):  osteoblastic activity
Calcitonin nasal spray (inhibits osteoclasts)

40. Treatment
Calcitonin nasal spray
(inhibits osteoclasts)
Duration = 6 weeks
200 IU / day
Especially vertebral fractures,
severe bone pains

41. Chelator MetalChelator
Toxic
ExcretionMetal
What is chelation therapy?

42. Overview of iron chelators
Property Deferoxamine (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.

43. Desferal is effective
Compliance is the issue

44. 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

45. 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

46. ICL 670

47. 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)

48. 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

49. WHAT & HOW WE MONITOR??
TYPE OF TEST ORGAN FREQUENCY
ECG/ 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

50. Dr. Rashid Merchant
Pediatrician
• Former Dean & Prof. Pediatrics
B.J. Wadia Child Hospital Mumbai
• Presently Consultant Pediatrician
Nanavati Hospital Mumbai

51. Hydroxyurea(Hu) Therapy
Hu is hydroxamic acid compound
Hu inhibits ribonucleotide reductase
Hu stimulates Y chain synthesis(B gene)
Increased Fetal Hb
Used in Rx - Sickle / Hb-pathies
Cytodrox(Cipla) 500mg/caps @ 10-20mg/kg/day
Effective minimal S/E. Safe for long term.
S/E:Anemia, Thrombocytopenia, Neutropenia.

52. Dr. 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.

53. Persevere through the difficult patches
and better times are sure to come
some time.