Thalassemia cpc

Saturday, February 8, 2014

pediatric department, Sheikh Zayed Medical
College/Hospital, Rahim Yar Khan, Punjab, Pakistan

1

A young boy known case of
“beta Thalassemia Major”

Resham kareem
Roll no “354”
Final year MBBS



3






Abdul Manan s/o Jamil Ahmad
6 years
Resident of Kott Samaba
Presented through Pediatrics Emergency on 1st Feb 2014



4



Fever



Vomiting



Altered level of consciousness



Yellowish discoloration of eyes and urine


2 days


1 day

5



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.



6



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.



7



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



8

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.



9

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



10

Pregnancy:
No history of infection, drug intake, trauma or irradiation to mother

Delivery:
Birth by uneventful SVD in Private hospital by a doctor



11

Breast feeding
•Exclusively breast fed for 6 months
Weaning
•Started at 7th month
•Contained daliya, cerelac, fruits
Current diet
•Home made food



12

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”


13

•
•
•
•
•
•

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.



14

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


15

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



16







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


17





water supply: proper and underground
Fresh water
Good sanitation



18

Behavior of Child:
Habit and interests:
Class
School performance:


positive
positive
two
good


19




Pt. received PARACETAMOL for fever in usual dose
Pt. also received FURECIMIDE for oliguria



20

EXAMINATION,

21

INVESTIGATIONS AND
MANAGEMENT

MUHAMMAD SALMAN
ROLL NO. 314
FINAL YEAR

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

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

Anthropometric measurements
Head

circumference: 51cm
Height: 107cm (5th centile)
Weight: 17 kg

24

25
•
•
•
•
•
•
•
•
•
•
•

Pallor
jaundice
POSITIVE
Bruises on skin
THALASSEMIC FACIES
clubbing
koilonychias,
NEGATIVE
leuconychia .
palmer erythema
Lymph node and thyroid are not palpable.
JVP not raised.
Ankle and sacral edema is absent.

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

•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.

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

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

Respiratory system
There is normal vesicular breathing on
auscultation with no added sounds.


30

Complete Blood Count

 Hb:

6.9gm/dl

 T.L.C:

5500/mm3

 Neutophil:

77%

 Lymphocyte:
 Eosinophils

; 4%

 monocytes:
 Platelets:

18%

1%

25,000/mm3

32

PERIPHERAL MORPHOLOGY
Dimorphic picture ++
 Microcytosis
++
 Hypochromic,
++
 anisocytosis,
++
 poikilocytosis,
+
 target cells few
 Schistiocytosis
 1 NRBC/ 100 WBCs
 Reticulocyte count : 3.8 %


33

Hb electrophoresis
Done at the age of 6 months
Hb F: 98.1 %
Hb A2: 1.9 %
Hb A: 0 %

34



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



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

37

Skull X-ray lateral view : thinning
of cortex and widening

38

CXR ------ heart size is normal

FINAL DIAGNOSIS
BETA THALLASEMIA MAJOR
WITH
complications
hepatic encephalopathy (stage II)
Hepatorenal syndrome/ARF

Hyperspleenism

39

40

TREATMENT GIVEN IN THE HOSPITAL

RIMSHA NAZIR
ROLL NO.201
FINAL YAER



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

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

THALASSEMIA
Dr. ZAHID
MEHMOOD
FCPS-II Resident
Pediatric Dept.

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


44

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

PUNJAB, PAKISTAN


compensatory rise in Hb F & Hb A2

45

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

PUNJAB, PAKISTAN


46

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
PUNJAB, PAKISTAN


47

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

PUNJAB, PAKISTAN


48

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
PUNJAB, PAKISTAN


49

BETA THALASSEMIA

PUNJAB, PAKISTAN


50

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”

PUNJAB, PAKISTAN


51

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.
PUNJAB, PAKISTAN


52

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.
PUNJAB, PAKISTAN


53

THALASSEMIA IN RAHIM YAR KHAN
(SZH)
Total thalassemic patients registered in SZH,RYK are
160
Total admissions 14433

2013

Thalassemia

PUNJAB, PAKISTAN

1335(9%)


54

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

PUNJAB, PAKISTAN


55

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

PUNJAB, PAKISTAN


56

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

PUNJAB, PAKISTAN


57

IRON OVER LOAD
Causes

•Hemolysis
•Increased hematopoiesis
•Increased absorption from GIT
•Repeated blood transfusion
PUNJAB, PAKISTAN


58

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
PUNJAB, PAKISTAN

growth) espc : Ye rs inia infections


59

CLINICAL FEATURES
INFANTS:

• Age of presentation: 6-9 mo (Hb F replaced by Hb A)
• Progressive pallor and jaundice
• Cardiac failure
• Fever
• Hepatomegaly
• Splenomegaly

PUNJAB, PAKISTAN


60

CLINICAL FEATURES
BY CHILDHOOD:

Severe anemia-cardiac dilatation
Jaundice
Transfusion dependent
Changes in skeletal system
 Growth retardation
PUNJAB, PAKISTAN


61

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


62

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

PUNJAB, PAKISTAN


63

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
PUNJAB, PAKISTAN


64

DIAGNOSIS
BLOOD PICTURE

•Hb – reduced (3-9mg/dl)
•RBC count – increased
•WBC, platelets – normal,
PUNJAB, PAKISTAN


65

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

PUNJAB, PAKISTAN


66

• Total. Bilirubin & Indirect. bilirubin –
increased

• B.M. study: hyperplastic erythropoiesis

PUNJAB, PAKISTAN


67

Hb ELECTROPHORESIS
Beta Thalassemia Major

Hb F: 98 %
Hb A2: 2 %
Hb A: 0 %
PUNJAB, PAKISTAN


68

X ray skull:
“ hair on end”
appearance
or
“crew-cut”
appearance
PUNJAB, PAKISTAN


69

IRON OVERLOAD ASSESSMENT

• S.Ferritin
• Urinary Fe excretion
• Liver biopsy - standard
• Myocardial-liver MRI indexes
PUNJAB, PAKISTAN


70

TREATMENT
• Supportive Treatment
• Psychological/social support
• Blood Transfusion
• Chelation Therapy ( For iron overload)
• Surgical
• Bone marrow transplant
• Newer therapy
PUNJAB, PAKISTAN


71

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

PUNJAB, PAKISTAN


72

PSYCHOLOGICAL/SOCIAL SUPPORT
• WISH
• BLOOD DONATION
• MORAL SUPPORT
• CHELATION THERAPY

PUNJAB, PAKISTAN


73

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 –

PUNJAB, PAKISTAN


74

CHELATION THERAPY
• ( 1 unit of blood contains 250 mg iron)

• DESFERRIOXAMINE
• DEFERIPRONE
• DEFERASIROX

PUNJAB, PAKISTAN


75

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
PUNJAB, PAKISTAN

Transplantation, Karach


76

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
PUNJAB, PAKISTAN


requirements (>180-200 ml/kg/yr) packed RBC

77

NEWER THERAPIES
• GENE MANIPULATION AND REPLACEMENT
• Hb F AUGEMENTATION

• Hydroxyurea
• Myelaran
• Butyrate derivatives
•
PUNJAB, PAKISTAN


78

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

PUNJAB, PAKISTAN


79

PREVENTION:

• Preventing marriage b/w traits
• Antenatal diagnosis
• Termination of pregnancy if Thalassemia
major
PUNJAB, PAKISTAN


80

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

PUNJAB, PAKISTAN


81

COMPLICATIONS….. continued
• Repeated infections
• Cardiac complications (Anemia , Hemosiderosis)
• Pericarditis
• Arrythmias
• Heart Block
•

CCF

PUNJAB, PAKISTAN


82

•
•
•
•
•
•
•
•
•
•
•

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
PUNJAB, PAKISTAN

Blood transfusion if there is anemia


83

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

PUNJAB, PAKISTAN


84

WHAT WE CAN DO FOR THIS PATIENT
FURTHER
• Chelation therapy
• Hb F augmentation
• Spleenectomy and vaccination
• Bone marrow transplantation
• Prevent other complications of thalassemia

PUNJAB, PAKISTAN


85

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.

PUNJAB, PAKISTAN


86

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
PUNJAB, PAKISTAN

order to detect earlier ,so intervention can be done.


87

W
HAT W AIM FOR THALASSEMIA
E

PUNJAB, PAKISTAN




88

.


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.

PUNJAB, PAKISTAN

PUNJAB, PAKISTAN


90

Thalassemia cpc

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