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Thalassemia cpc
1. Saturday, February 8, 2014
pediatric department, Sheikh Zayed Medical
College/Hospital, Rahim Yar Khan, Punjab, Pakistan
1
2. A young boy known case of
“beta Thalassemia Major”
3. Resham kareem
Roll no “354”
Final year MBBS
Saturday, February 8, 2014
pediatric department, Sheikh Zayed Medical
College/Hospital, Rahim Yar Khan, Punjab, Pakistan
3
4.
Abdul Manan s/o Jamil Ahmad
6 years
Resident of Kott Samaba
Presented through Pediatrics Emergency on 1st Feb 2014
Saturday, February 8, 2014
pediatric department, Sheikh Zayed Medical
College/Hospital, Rahim Yar Khan, Punjab, Pakistan
4
5.
Fever
Vomiting
Altered level of consciousness
Yellowish discoloration of eyes and urine
Saturday, February 8, 2014
2 days
pediatric department, Sheikh Zayed Medical
College/Hospital, Rahim Yar Khan, Punjab, Pakistan
1 day
5
6.
Patient is a known case of Beta Thalassemia Major diagnosed at
the age of 6 months.
He was in his usual state of health 2 days back when he
developed high grade fever which was sudden in onset,,
intermittent and not associated with rigors and chills, flu, and
cough. Fever was relieved by medication.
Fever was associated with vomiting, 2-3 times per day, vomitus
was yellow in color and contained food particles but no h/o blood
in vomitus.
Saturday, February 8, 2014
pediatric department, Sheikh Zayed Medical
College/Hospital, Rahim Yar Khan, Punjab, Pakistan
6
7.
He developed altered level of consciousness and irritable
behavior. It was associated with drowsiness, confusion,
disorientation and mood swings.
My patient developed yellow discoloration of eyes and urine ,
which was associated with itching and bruises.
Saturday, February 8, 2014
pediatric department, Sheikh Zayed Medical
College/Hospital, Rahim Yar Khan, Punjab, Pakistan
7
8.
There was H/O poor intake of both liquid and solid.
CVS:
There is H/O breathlessness on exertion but no Edema feet or cyanosis.
Respiratory system:
No H/O cough, wheezing or chest pain
GUS:
There is H/O Pain in flank, dysuria, oliguria and yellow colored urine
GIT
There is no H/O of diarrhea, constipation, hematemesis or melena, clay
colored stool
Saturday, February 8, 2014
pediatric department, Sheikh Zayed Medical
College/Hospital, Rahim Yar Khan, Punjab, Pakistan
8
9. CNS:
No H/O of fits, visual loss and weakness.
Endocrine
No H/O polydipsia, polyphagia, heat or cold intolerance.
Locomoter system
There is no H/O of joint pain, swelling and stiffness of joint.
Saturday, February 8, 2014
pediatric department, Sheikh Zayed Medical
College/Hospital, Rahim Yar Khan, Punjab, Pakistan
9
10. Diagnosis
At 6 month of age diagnosed as Thalassemia Major in SZH,RYK
when he presented with progressive pallor, fever and vomiting.
Transfusion History
Blood transfusion started from 6 months of life.
First 3 years, transfusion at monthly interval
Afterwards, transfusion at 15 days interval.
Chelation therapy
Never taken yet because of no awareness
Saturday, February 8, 2014
pediatric department, Sheikh Zayed Medical
College/Hospital, Rahim Yar Khan, Punjab, Pakistan
10
11. Pregnancy:
No history of infection, drug intake, trauma or irradiation to mother
Delivery:
Birth by uneventful SVD in Private hospital by a doctor
Saturday, February 8, 2014
pediatric department, Sheikh Zayed Medical
College/Hospital, Rahim Yar Khan, Punjab, Pakistan
11
12. Breast feeding
•Exclusively breast fed for 6 months
Weaning
•Started at 7th month
•Contained daliya, cerelac, fruits
Current diet
•Home made food
Saturday, February 8, 2014
pediatric department, Sheikh Zayed Medical
College/Hospital, Rahim Yar Khan, Punjab, Pakistan
12
13. major milestones achieved
Smile:
1 month
Neck holding:
3 months
Sitting
7 months
Crawling: 10 months
Standing:
1 year
Walking: 15 months
Talking single word: 1 year
Accurate speech:
1.5 years
“All milestones achieved at normal age”
Saturday, February 8, 2014
pediatric department, Sheikh Zayed Medical
College/Hospital, Rahim Yar Khan, Punjab, Pakistan
13
14. •
•
•
•
•
•
BCG
penta 1, OPV 1,
Penta 2, OPV 2,
Penta 3, OPV 3,
Measles I
Measles II
at Birth
06 wks
10 wks
14 wks
09 months
15 months
Immunization status complete
according to EPI schedule.
Saturday, February 8, 2014
pediatric department, Sheikh Zayed Medical
College/Hospital, Rahim Yar Khan, Punjab, Pakistan
14
15. Age of mother: 35 years
Age of father: 40 years
Both are confirmed cases of Thalassemia Minor
Cousin Marriage
4 live siblings
1st sibling: M, 9 yrs., known case of Thalassemia Major
2nd sibling: M, 7 yrs, known case of Thalassemia Minor
3rd & 4th: twin F, 2 yrs, known case of Thalassemia Minor
Saturday, February 8, 2014
pediatric department, Sheikh Zayed Medical
College/Hospital, Rahim Yar Khan, Punjab, Pakistan
15
16. There is no other history of hereditary or infectious
disease
Death:
1st immediately after birth(cause unknown)
2nd spontaneous abortion at 4th month of gestation
Saturday, February 8, 2014
pediatric department, Sheikh Zayed Medical
College/Hospital, Rahim Yar Khan, Punjab, Pakistan
16
17.
Education of parents:
Mother: Intermediate
father: matriculation
Occupation:
father: shopkeeper
Monthly Income: 30,000 PKR
House: pukka
2 rooms
locality: village
sanitary condition: good
Blood is donated by the blood bank of SZH,RYK
Saturday, February 8, 2014
pediatric department, Sheikh Zayed Medical
College/Hospital, Rahim Yar Khan, Punjab, Pakistan
17
18.
water supply: proper and underground
Fresh water
Good sanitation
Saturday, February 8, 2014
pediatric department, Sheikh Zayed Medical
College/Hospital, Rahim Yar Khan, Punjab, Pakistan
18
19. Behavior of Child:
Habit and interests:
Class
School performance:
Saturday, February 8, 2014
positive
positive
two
good
pediatric department, Sheikh Zayed Medical
College/Hospital, Rahim Yar Khan, Punjab, Pakistan
19
20.
Pt. received PARACETAMOL for fever in usual dose
Pt. also received FURECIMIDE for oliguria
Saturday, February 8, 2014
pediatric department, Sheikh Zayed Medical
College/Hospital, Rahim Yar Khan, Punjab, Pakistan
20
22. Examination at the time of admission
22
6 year old child pale looking having jaundice,
not oriented, irritable, drowsy & some
dehydrated having vitals
H/R
110/min
R/R
24/min
temp 102 F
BP
85/60 mm of Hg
23. General physical examination
(current)
Abdul Manan, 6 year old boy, average built,
Well cooperative and well oriented in time, place and
person lying comfortably in the bed.
No obvious
dysmorphism
respiratory
distress,
cyanosis
Pulse rate:
92/min
Respiratory rate:
18/min
Blood pressure:
100/65 mm of Hg
Temperature:
99 F
and
26. GIT
26
Orodental hygiene is satisfactory with protrusion of maxillary teeth
ABDOMINAL EXAMINATION
INSPECTION abdomen is distended, moving with respiration with no stria,
scar mark, dilated veins. Umbilicus is central and inverted, hernial orifices
are intact.
PALPATION there is no tenderness,
liver is palpable 8cm below the Right costal margin in
midclavicular
line, firm in consistency, sharp edges, upper border is in 5th ICS with a
total span of 14.4 cm.
Spleen is also enlarged measuring 10cm below the costal margins , firm
in consistency with sharp edges
Kidneys are impalpable bimanually
bladder not distended
27. 27
•PERCUSSION note is resonant all over except in the region of
liver and spleen, where it is dull.
no shifting dullness and fluid thrill
•AUSCULTATION : bowel sounds are audible,
no bruit is audible.
28. CVS
28
INSPECTION: apex beat is not visible, there are no pulsation,
prominent veins or scar
PALPATION: apex beat is palpable in 5th intercostal space medial to
mid clavicular line and is of normal character. No other sounds, thrill
or left parasternal heave is palpable.
AUSCULTATION: 1st and 2nd heart sounds are of normal character with
no added sound
29. CNS
29
Higher mental functions are intact.
Speech is normal.
Cranial nerves are intact
Motor and sensory systems are normal
No sign of meningeal irritation are present.
Gait is normal
GROSSLY INTACT
35.
Serum ferritin level:
>2000ng/ml (normal-less than 400)
Serum LFT’s: Bilirubin=9.5mg/dl
ALT=1261 IU/l
AST=739 IU/l
Serum alkaline phosphatase=486U/L
Serum albumin = 3 g/dl
Serum RFT’s: Blood urea= 203 mg/dl
Creatinine= 1.4 mg/dl
PT : control 18,
test
14
APTT : control 39
test
33
35
36.
Serum electrolyte: Sodium=131mmol/L
36
Potassium=3.4mmol/L
ECG ----- normal
Ultrasound of abdomen: hepatospleenomegaly, PV vein size is normal
Anti HCV: positive , HbSAg: negative (result for anti HCV by ELISA awaited)
Complete urine examination : pus cell 4-6/hpf
albumin +
Blood sugar (random): 90 mg/dl
Thyroid function test
T4
TSH
1.39ng/dl
4.41µIU/ml
normal
41.
MAINTENANCE OF ABC and monitoring of vitals
NG tube and foley catheter passed
Hydration
I/V antibiotics
Lactulose
Enema
Vit. K
Aminoglycoside through NG tube
Cimetidine
Blood transfusion
41
42. TREATMENT OUTCOME
07.02.2014
Now pt. is fully conscious, co-operative, oriented in time, space and
person with stable vitals.
His current investigations
LFTs bilirubin 3.7 mg/dl
ALT
272 IU/L
AST
129 IU/L
Al.phos 326 IU/L
CBC
Hb.
7.7 g/dl
RFTs
urea
32 mg/dl
Creatinine
0.8mg/dl
blood transfusion advised
42
44. INTRODUCTION
BASIC 3 TYPES
•Hb A
•Hb A2
•Hb F
2α + 2β
2α + 2δ
2α + 2γ
1.The α-globin genes are encoded on chromosome 16 ,
2. γ, δ, and β-globin genes are encoded on chromosome 11
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
Saturday, February 8, 2014
44
45. fetal period
1ST TRIMESTER HB F ,2nd trimester Hb A, 3rd trimester
Hb A2
At birth appears Hb F 98% gradually decline till 6months
At 6 months
Hb A >95%,
Hb A2 ≤3.5 %,
Hb F <1.5%.
•If synthesis of α chain is suppressed – level of all 3 normal
Hb A (2α ,2β), A2 (2α ,2 δ),F(2α ,2γ) are reduced
•If β chain is suppressed
- Hb A (2α ,2β), is suppressed
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
Saturday, February 8, 2014
compensatory rise in Hb F & Hb A2
45
46. DEFINITION
• Thalassemia syndromes are a heterogeneous group of inherited
anemias characterized by reduced or absent synthesis of either
alpha or Beta globin chains.
• One of the most common single gene disorders
ETIOLOGY
• Autosomal recessive
• Mutations
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
Saturday, February 8, 2014
46
47. CLASSIFICATION OF THALASSEMIAS
• β Thalassemia
• α Thalassemia
• γ Thalassemia
• δ Thalassemia
• δ β Thalassemia
• Hemoglobin Lepore
syndrome
• Hb C Thalassemia
• Hb D Thalassemia
(Punjab)
• Hb E Thalassemia
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
Saturday, February 8, 2014
47
48. Αlpha-THALASSEMIA
NO. OF
GENES
PRESENT
GENOTYPE
CLINICAL CLASSIFICATION
4 genes
3 genes
2 genes
αα/αα
αα/- α
- α/- α
αα/- - α/- - -/- -
Normal
Silent carrier
α thalassemia trait
1 gene
0 genes
or
Hb H Disease
Hb Barts / Hydrops
fetalis
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
Saturday, February 8, 2014
48
49. ALPHA THALASSEMIA
• Highest prevalence in Thailand
• α chains shared by fetal as well as adult life. Hence manifests
in both
• These thalassemias don’t have ineffective erythropoiesis
because β and γ tetramers are soluble chains and hence not
destroyed always
• Silent carrier – not identified hematologically,
• Diagnosed when progeny has Hb Barts/ Hb H
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
Saturday, February 8, 2014
49
51. HISTOTY
Dates back over 50,000 year ago in a valley of Italy and
Greece now covered by the Mediterranean.
Thalassemia is a Greek word
Thalassa which means the sea (Refer to the Mediterranean)
emia which means “related to blood”
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
Saturday, February 8, 2014
51
52. EPIDEMIOLOGY
Worldwide ,15million have clinically apparent
thalassemic disorders
About 100,000 babies worldwide are born with
thalassemia each year.
Globally in 2010 it resulted in about 18,000 deaths
Genetic disorder of hemoglobin are the commonest
single gene disorder in Pakistan.
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
Saturday, February 8, 2014
52
53. THALASSEMIA IN PAKISTAN
In Pakistan the disease is seen in almost all the parts of country,
with an estimated carrier rate of 5-8% ( About 9.8 million carriers in
total population)
Approximately 4000-5000 beta thalassemia children are born each
year.
Average life expectancy in Pakistan is 10 years.
At present disease load is around 100,000 patients throughout the
country.
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
Saturday, February 8, 2014
53
54. THALASSEMIA IN RAHIM YAR KHAN
(SZH)
Total thalassemic patients registered in SZH,RYK are
160
Total admissions 14433
2013
Thalassemia
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
1335(9%)
Saturday, February 8, 2014
54
55. β/
β
Normal
CLASSIFICATION OF Β THALASSEMIA
CLASSIFICATIO GENOTYPE
N
CLINICAL
SEVERITY
β thal
minor/
trait
β / +,
β
β/ 0
β
Silent
β thal
intermedia
β + / +,
β
β +/ 0
β
Moderate
β thal major
β 0/β 0
Severe
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
Saturday, February 8, 2014
55
56. PATHOPHYSIOLOGY
• Since ẞ chain synthesis reduced
-
1. gamma 2 ץand delta δ2 chain combines with normally
produced α chains ( Hb F (α2 2 , )ץHb A2 (α2 δ2) - Increased
production of Hb F and Hb A2
2. Relative excess of α chains → α tetramers forms
aggregates → precipitate in red cells → inclusion bodies
→ premature destruction of maturing erythroblasts within
the marrow (Ineffective erythropoiesis) or in the
periphery (Hemolysis)→ destroyed in spleen
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
Saturday, February 8, 2014
56
57. PATHOPHYSIOLOGY….. continued
Anemia result from lack of adequate Hb A →
tissue hypoxia→ ↑
EPO production → ↑
erythropoiesis in the marrow and sometimes
extramedullary → expansion of medullary
cavity of various bones
Liver spleen enlarge → extramedullay
hematopoiesis
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
Saturday, February 8, 2014
57
58. IRON OVER LOAD
Causes
•Hemolysis
•Increased hematopoiesis
•Increased absorption from GIT
•Repeated blood transfusion
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
Saturday, February 8, 2014
58
59. ACCUMULATION OF IRON
• Deposition in pituitary - endocrine disturbance - short
stature, delayed puberty, poor sec. sexual characteristics
• Hemochromatosis - cirrhosis of liver
• Cardiomyopathy (cardiac hemosiderosis) -cardiac failure
• Deposition in pancreas -diabetes mellitus
• Lungs: restrictive lung defects
• Adrenal insufficiency
• Hypothyroidism, hyperparathyroidism
• Increased susceptibity to infections (iron favours bacterial
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
growth) espc : Ye rs inia infections
Saturday, February 8, 2014
59
60. CLINICAL FEATURES
INFANTS:
• Age of presentation: 6-9 mo (Hb F replaced by Hb A)
• Progressive pallor and jaundice
• Cardiac failure
• Fever
• Hepatomegaly
• Splenomegaly
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
Saturday, February 8, 2014
60
61. CLINICAL FEATURES
BY CHILDHOOD:
Severe anemia-cardiac dilatation
Jaundice
Transfusion dependent
Changes in skeletal system
Growth retardation
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
Saturday, February 8, 2014
61
62. SKELETAL CHANGES
THALASSEMIC FACIES
Frontal bossing, maxillary hypertrophy, depression of nasal bridge ,
Malocclusion of teeth
PARAVERTEBRAL MASSES:
•
•
•
•
•
Broadening of ribs at costo-vertebral attachment
Paraparesis
PATHOLOGICAL FRACTURES:
Cortical thinning
Increased porosity of long bones
DELAYED PNEUMATISATION OF SINUSES - sinusitis
PEDIATRIC DEPARTMENT, SHEIKH ZAYED
PREMATURE FUSION MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
OF EPIPHYSES - Short
PUNJAB, PAKISTAN
stature
Saturday, February 8, 2014
62
63. CLINICAL FEATURES (THALASSEMIA
INTERMEDIA)
• Moderate pallor, usually maintains Hb >6gm%
• Anemia worsens with pregnancy and infections (erythroid
stress)
• Less transfusion dependant
• Skeletal changes present, progressive splenomegaly
• Growth retardation
• Longer survival than Thalassemia major
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
Saturday, February 8, 2014
63
64. CLINICAL FEATURES
(THALASSEMIA MINOR)
• Usually ASYMPTOMATIC
• Mild pallor, no jaundice
• No growth retardation, no skeletal abnormalities, no splenomegaly
• MAY PRESENT AS REFRACTORY IRON DEFICIENCY ANEMIA
(Hypochromic microcytic anemia)
• Unresponsive/ refractory to Fe therapy
• Normal life expectancy
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
Saturday, February 8, 2014
64
65. DIAGNOSIS
BLOOD PICTURE
•Hb – reduced (3-9mg/dl)
•RBC count – increased
•WBC, platelets – normal,
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
Saturday, February 8, 2014
65
66. PERIPHERAL BLOOD PICTURE
• RBC indices – MCV & MCH,MCHC reduced
• microcytic hypochromic anemia, anisopoikilocytosis, target cells,
nucleated RBC, leptocytes, basophilic stippling, tear drop cells
• Cytoplasmic incl bodies in α thal
• Post splenectomy : Howell-Jolly and Heinz bodies
• Reticulocyte count increased (upto 10%) but Relative
Reticulocytopenia
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
Saturday, February 8, 2014
66
67. • Total. Bilirubin & Indirect. bilirubin –
increased
• B.M. study: hyperplastic erythropoiesis
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
Saturday, February 8, 2014
67
68. Hb ELECTROPHORESIS
Beta Thalassemia Major
Hb F: 98 %
Hb A2: 2 %
Hb A: 0 %
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
Saturday, February 8, 2014
68
69. X ray skull:
“ hair on end”
appearance
or
“crew-cut”
appearance
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
Saturday, February 8, 2014
69
70. IRON OVERLOAD ASSESSMENT
• S.Ferritin
• Urinary Fe excretion
• Liver biopsy - standard
• Myocardial-liver MRI indexes
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
Saturday, February 8, 2014
70
71. TREATMENT
• Supportive Treatment
• Psychological/social support
• Blood Transfusion
• Chelation Therapy ( For iron overload)
• Surgical
• Bone marrow transplant
• Newer therapy
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
Saturday, February 8, 2014
71
72. SUPPORTIVE TREATMENT
• Vitamin C – increases iron excretion
• Restrict Fe intake – decrease meat, liver, spinach
• Folate – 1 mg/day
• Genetic counselling
• Psychological support
• Hormonal therapy – GH, estrogen, testosterone,
thyroxin
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
Saturday, February 8, 2014
72
73. PSYCHOLOGICAL/SOCIAL SUPPORT
• WISH
• BLOOD DONATION
• MORAL SUPPORT
• CHELATION THERAPY
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
Saturday, February 8, 2014
73
74. BLOOD TRANSFUSION
• BT at 4-6 wks interval
Packed RBC, leucocyte-poor
• Hb to be maintained – (Hb >10.5 gm/dl)
• If regular transfusions and chelation - no hepatomegaly, no
facies
• 10-15ml/kg RBC raises Hb by 3-5gm/dl –
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
Saturday, February 8, 2014
74
75. CHELATION THERAPY
• ( 1 unit of blood contains 250 mg iron)
• DESFERRIOXAMINE
• DEFERIPRONE
• DEFERASIROX
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
Saturday, February 8, 2014
75
76. BONE MARROW TRANSPLANTATION
•
•
•
•
•
Severely affected child
Minimum transfusions
No iron toxicity
Age usually < 5 years
HLA identical donor (sib)
• Risk factors:
Hepatomegaly >2cm
Portal fibrosis
Iron overload
Older age
• Success rate In low risk young patients, the 5yr thalassemia free survival
rate is 73 -94% at National Institute of Blood Disease & Bone Marrow
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
Transplantation, Karach
Saturday, February 8, 2014
76
77. SURGICAL TREATMENT - SPLENECTOMY
• Deferred as long as possible. At least till 5-6 yrs age
• Spleenectomy (indications):
• Hyperspleenism
(spleenomegaly+mono/bi/pancytopenia)
• Massive splenomegaly causing mechanical
discomfort
• Progressively increasing blood transfusion
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
Saturday, February 8, 2014
requirements (>180-200 ml/kg/yr) packed RBC
77
78. NEWER THERAPIES
• GENE MANIPULATION AND REPLACEMENT
• Hb F AUGEMENTATION
• Hydroxyurea
• Myelaran
• Butyrate derivatives
•
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
Saturday, February 8, 2014
78
79. PRENATAL DIAGNOSIS
• β/α ratio: <0.025
in fetal
blood – Thal. major
• Chorionic villous biopsy at
10-12 wks
• amniocentesis at 15-18th wk
gestation Analysis of fetal
DNA
•
PCR to detect β globin
gene
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
Saturday, February 8, 2014
79
80. PREVENTION:
• Preventing marriage b/w traits
• Antenatal diagnosis
• Termination of pregnancy if Thalassemia
major
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
Saturday, February 8, 2014
80
81. COMPLICATIONS
• Hypersplenism ------- surgery
• Bleeding Diathesis--- FFP
• Hemosiderosis ------- chelation therapy
• Hepatitis and hepatic encephalopathy
• Pathological Fractures
• Growth Retardation
• Diabetes Mellitus
• Failure to attain Puberty
• Complications of Repeated Blood Transfusions
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
Saturday, February 8, 2014
81
82. COMPLICATIONS….. continued
• Repeated infections
• Cardiac complications (Anemia , Hemosiderosis)
• Pericarditis
• Arrythmias
• Heart Block
•
CCF
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
Saturday, February 8, 2014
82
83. •
•
•
•
•
•
•
•
•
•
•
MANAGEMENT OF HEPATIC
ENCEPHALOPATHY
MAINTENANCE OF ABC and monitoring of vitals and protein restriction
NG tube and foley catheter passed
Gastric lavage if malena or haemetemesis
I/V antibiotics for infection
Lactulose to change gut flora
Enema for constipation
Hydration
Vit. K
Oral Aminoglycoside / Metronidazole
H2 blocker/ PPI
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
Blood transfusion if there is anemia
Saturday, February 8, 2014
83
84. HEPATORENAL SYNDROME
• Hepatic failure, hypernatremia, hypokalemia, oliguria, deranged RFTs
• Two types
type 1 – acute
type II -- chronic
• Withdrawal of nephrotoxic drugs
• Renal function recovers if hepatic function improves
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
Saturday, February 8, 2014
84
85. WHAT WE CAN DO FOR THIS PATIENT
FURTHER
• Chelation therapy
• Hb F augmentation
• Spleenectomy and vaccination
• Bone marrow transplantation
• Prevent other complications of thalassemia
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
Saturday, February 8, 2014
85
86. CAUSES OF DEATH IN THALASSEMICS
• The most common cause of death in older children was
heart disease(cardiomyopathy)
followed by infection &liver disease.
• While in younger children
infections outnumber the cardiac complications.
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
Saturday, February 8, 2014
86
87. KEY MESSAGE
•Prevention is better than cure
•
Better to prevent thalassemia.
• IF not, Better to prevent complications of thalassemia.
• How:
By monitoring patients clinically & by investigations in
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
order to detect earlier ,so intervention can be done.
Saturday, February 8, 2014
87
88. W
HAT W AIM FOR THALASSEMIA
E
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
Saturday, February 8, 2014
88
89. .
It was like a dream come true for 12-year old Naima Gul, resident ofFebruary 8, 2014 Swat, 89
when
Saturday, Mingora,
she became the first female pilot of the Pakistan.
PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
90. PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN,
PUNJAB, PAKISTAN
Saturday, February 8, 2014
90
Editor's Notes
Listen to the mother,
What are her worries?
What does she think is the problem?
Ask her to define her terms?
Quote verbatim what she says.
Understand her idioms.
The HBB gene provides instructions for making a protein called beta-globin.
When there is a mutations in the HBB gene, it prevents the production of any beta-globin.
The absence of beta-globin is referred to as beta-zero (B0) thalassemia.
Other HBB gene mutations allow some beta-globin to be produced but in reduced amounts. A reduced amount of beta-globin is called beta-plus (B+) thalassemia.
HEPATOMEGALY
Extra medullary erythropoiesis
Iron released from breakdown of endogenous or transfused RBCs cannot be utilized for Hb synthesis – hemosiderosis
Hemochromatosis
Infections – transfusion related - Hep B,C, HIV
Chronic active hepatitis
Infection causes
Poor nutrition
Increased iron in body
Blockage of monocyte-macrophage system
Hypersplenism- leukopenia
Infections associated with transfusions
Iron-chelating agents: desferrioxamine-
Dose: 30-60mg/kg/day
IV / s/c infusion pump over 12 hr period 5-6 days /wk
Start when ferritin >1000ng/ml
Best >5 yrs
Vitamin C 200 mg on day of chelation - enhances DFO induced urinary excretion of Fe
Adverse effects
Cardiotoxicity – arrythmias
Eyes - cataract
Ears - sensorimotor hearing loss
Bone dysplasia-growth retardation
Rapid infusion- histamine related reaction- hypotension, erythema, pruritis
Infection, sepsis
DEFERIPRONE
Oral chelator - > 2yrs old Dose: 50-100mg/kg/day
Adverse effects:
Reversible arthropathy
Drug induced lupus
Agranulocytosis
Other oral chelators
Deferrothiocine
Pyridoxine hydrazine
ICL-670 – removes Fe from myocardial cells