Case Management

General data
patient J.D
Boy, Filipino, Catholic
8 years old, born on January
9, 2007
Calasiao, Pangasinan
Was admitted regular every
2 month
Admitted on May 29,2015

CHIEF COMPLAINT:

Pallor

History Present illness

3 months
old

He experienced pallor accompanied with

fever vomiting, weakness and
abdominal distension
Then consultation was done and
splenomegaly was noted.

6 months
old

He still experienced pallor accompanied

with fever vomiting and abdominal
distension
He was started blood transfusion every
months at R1MC.

History Present illness

He was refer to UST hospital and
was diagnosed of BetaThalassemia,major.
10
months Then he had regular schedule
monthly blood transfusion.
old
Then patient was admitted to R1MC
monthly for blood transfusion of
PRBC
Patient was given Deferasirox once
a day

History Present illness

until October 16,2014, he was
scheduled for splenectomy and it was
done at PCMC.

Then patient was admitted to R1MC

every 2 month for blood transfusion
of PRBC
Patient was given Deferasirox once a
day

History Present illness

Few hour
PTA

The patient experience

pallor without any
associated signs or
symptoms
He was brought to R1MC,
hence admitted for blood
transfusion
Patient was given
Deferasirox and Folic acid
once a day

Immunization
History

Past Medical illness

6 months old, he
was diagnosed
Asthma
Salbutamol
inhaler for
Reliever, PRN

Pneumococcal
Meningococcal
Hib
BCG 1 dose
HBV 2 dose
DTP 3 dose
OPV 3 dose
MMR 2 dose

Family history
Hypertension
Blood disorder

Social/Environme
ntal
Live with
parents
Semi concrete
house type
his diet mostly
consisted of
meat and
vegetables
Mineral water

Review of system
skin
(+)Pallor

Physical Examination
The patient is alert, consciousness and
cooperative, and not in cardiopulmonary
distress. He is oriented to time,place and
person
Vital Signs:
Temperature (axillary): 36.8C
Respiratory Rate: 24cpm
Heart rate: 108bpm
Blood pressure : 90/60 mmHg

Anthropometric measurement:
Weight: 22 kg
Height: 120 cm
BMI : 15.28

Physical Examination
Skin and Nails
(+) Pallor. No jaundice.
good skin turgor
Capillary refill time: 2 seconds

HEENT
There are no scalp deformities.
(+) Pale conjunctiva
(+) Pale buccal mucosa
no tonsillopharyngeal congestion

Physical Examination
Chest and Lungs
Symmetrical chest expansion.
(-) retraction, (-) Lagging
Clear breath sounds

Cardiovascular
Adynamic precordium, Normal rate,
regular rhythm, (-)murmurs, (-)heave
and thrill

Physical Examination
Abdomen:
globular, scars at left upper quadrant
16 cms
Normal active Bowel movement.
Hepatomegaly, liver span 10.5cms
at MCL

Genitalia and Anus

Grossly male

Extremities

Neurologic Examination
Cerebrum : Oriented to person, time, place
GCS 15
Cerebellum : (-)Nystagmus
Cranial Nerve
5/5 5/5 : intact
Motor

5/5

5/5

Sensory

Signs of Meningeal irritation

(-)Kernigs sign
(-)brudzinski sign
(-)Nuchal rigidity

100%

100%

100%

100%

Diagnosis
Beta Thalassemia, Major

Diagnostics
Pre-BT

Post-BT

WBC
73.41x10^9/L(1
7.8%N, 75.7%L)
RBC
2.69x10^12/L
HGB 73 g/L
HCT 0.21
MCV 80.6 fL
PLT 337x10^9 /L

WBC
60.04x10^9/L(2
7.4%N, 65.1%L)
RBC
4.15x10^12/L
HGB 112 g/L
HCT 0.33
MCV 80.6 fL
PLT 343x10^9 /L

Therapeutics
1 UNIT PRBC
Furosemide 0.5 mg/kg, 1 dose,
post Blood transfusion

Beta-THALASSEMIA

Population
3% of the worlds population
carry genes for BetaThalassemia
5-10% in Southeast Asia

DEFINTION
Thalassemia sydromes are a
heterogenous group of inherited
anemias characterised by reduced
or absent synthesis of either alpha
or Beta globin chains of Hb A
Most common single gene disorder

BASICS - 3 types of Hb
1. Hb A - 2 and 2 chains
97% adult Hb
Postnatal life Hb A replaces Hb F by 6 months
2. Fetal Hb (HbF) - 2 and 2 chains
1% of adult Hb
70-90% at term. Falls to 25% by 1st month and
progressively
3. Hb A2 - 2 and 2 chains
1.5 3.0% of adult Hb

INHERITANCE
Autosomal
recessive
Beta thal - point
mutations on
chromosome 11
Alpha thal - gene
deletions on
chromosome 16

Classification
If synthesis of chain is
suppressed level of all 3 normal
Hb A (2 ,2),A2 (2 ,2 ),F(2 ,
2) reduced alpha thalassemia
If chain is suppressed - adult Hb
is suppressed - beta thalassemia

CLASSIFICATION
-thalassemia
Hb H (4)
Hb-Barts (4)

-thalassemia
+ thal : reduced synthesis of globin chain,
heterozygous
0 thal : absent synthesis of globin chain,
homozygous------ Hb A - absent
Hb F (2 2)
Hb A2 (2 2)

CLASSIFICATION OF THALASSEMIA
CLASSIFICATI GENOTYPE
ON

CLINICAL
SEVERITY

thal
minor/trait

/+, /0

Silent

thal
intermedia

+ /+, +/0 Moderate

thal major

0/ 0

Severe

PATHOPHYSIOLOGY
Since chain synthesis reduced 1. gamma 2 and delta 2 chain combines
with normally produced chains ( Hb F ( 2
2 ), Hb A2 (2 2) - Increased production of Hb F
and Hb A2

2. Relative excess of chains 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

PATHOPHYSIOLOGY
Anemia result from lack of adequate
Hb A tissue hypoxiaEPO
production erythropoiesis in
the marrow and sometimes
extramedullary expansion of
medullary cavity of various bones
Liver spleen enlarge
extramedullay hematopoiesis

EFFECTS OF MARROW
EXPANSION
Pathological fractures due to cortical
thinning
Deformities of skull and face
Sinus and middle ear infection due to
ineffective drainage
Folate deficiency
Hypermetabolic state -> fever, wasting
Increased absorption of iron from intestine

HEPATOMEGALY
Extra medullary erythropoeisis
Iron released from breakdown of
endogenous or transfused RBCs
cannot be utilized for Hb synthesis
hemosiderosis
Hemochromatosis
Infections transfusion related Hep B,C, HIV

SPLENOMEGALY
Extra medullary
hematopoeisis
Work hypertrophy due to
constant hemolysis
Hypersplenism
(progressive splenomegaly)

INFECTIONS -CAUSES
Poor nutrition
Increased iron in body
Blockage of monocyte-macrophage
system
Hypersplenism- leukopenia
Infections associated with
transfusions

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,
sterile pericarditis, arrythmias, heart
block

ACCUMULATION OF
IRON
Lungs: restrictive lung defects
Adrenal insufficiency
Hypothyroidism,
hypoparathyroidism
Increased susceptibity to
infections (iron favours bacterial
growth) espc : Yersinia infections

CLINICAL FEATURES
(THAL MAJOR)
INFANTS:
Age of presentation: 6-9 mo
(Hb F replaced by Hb A)
Progressive pallor and jaundice
Cardiac failure
Failure to thrive, gross motor delay
Feeding problems
Bouts of fever and diarrhea
Hepatosplenomegaly

CLINICAL FEATURES
(THAL MAJOR)
BY CHILDHOOD:

Growth retardation
Severe anemia-cardiac dilatation
Transfusion dependant
Icterus
Changes in skeletal system

SKELETAL CHANGES
CHIPMUNK FACIES (HEMOLYTIC FACIES):
Frontal bossing, maxillary hypertrophy, depression of nasal
bridge , Malocclusion of teeth
PARAVERTEBRAL MASSES:
Broad expansion of ribs at vertebral attachment
Paraparesis
PATHOLOGICAL FRACTURES:
Cortical thinning
Increased porosity of long bones
DELAYED PNEUMATISATION OF SINUSES
PREMATURE FUSION OF EPIPHYSES -

Short stature

Others
Delayed menarche
Gall-stones, leg ulcers
Pericarditis
Diabetes/ cirrhosis of liver
Evidence of hypersplenism

DIAGNOSIS
BLOOD PICTURE
Hb reduced (3-9mg/dl)
RBC count increased
WBC, platelets normal
RBC indices
MCV & MCH,MCHC reduced
RDW normal

BLOOD PICTURE
microcytic hypochromic anemia,
anisopoikilocytosis, target cells,
nucleated RBC, leptocytes, basophilic
stippling, tear drop cells
Cytoplasmic increase bodies in thal
Post splenectomy : Howell-Jolly and
Heinz bodies
Reticulocyte count increased (upto 10%)

Normal RBC
Hypochromic-Microcyt

DIAGNOSIS
Results
T. bilirubin, I. bilirubin

Increased

Haptoglobulin and
hemopexin

depleted

B.M. study

hyperplastic erythropoiesis

Red cell survival

decreased

Folate levels

concurrently decreased

Free erythrocyte porphyrin

normal

Serum uric acid

raised

Haemosiderinuria

DIAGNOSIS Hb
ELECTROPHORESIS
Thalassemia, Major - Hb F: 98 %
Hb A2: 2 %
Hb A: 0 %
MAJOR

MINOR

NORMAL

HEMOGLOBIN
Hb F

10-98%

variable

<1%

Hb A

Absent

80-90%

97%

Hb A2

variable

5-10%
(increased)

1-3%

Radiological changes
Small bones (hand ) earliest bony change,
rectangular appearance,medullary portion of
bone is widened &bony cortex thinned out
with coarse trabecular pattern in medulla
Skull widened diploid spaces interrupted
porosity gives hair on end appearance
Delayed pneumatization of sinuses maxilla
appears overgrown with prominent malar
eminences

X ray skull:
hair on end
appearance
or
crew-cut
appearance

Treatment:
BT at 4-6 wks interval (Hb~ 9.5 gm/dl)

Packed RBC, leucocyte-poor

Hb to be maintained
Hypertransfusion : >10 gm/dl
Supertransfusion : >12 gm/dl
If regular transfusions- no hepatomegaly, no
facies
10-15ml/kg PRBC raises Hb by 3-5gm/dl

Neocytes transfusion
Mean cell age : 30 days
2-4 times more expensive

TREATMENT SPLENECTOMY
Deferred as long as possible. At least till 5-6
yrs age

Splenectomy (indications):
Massive splenomegaly causing
mechanical discomfort
Progressively increasing blood
transfusion requirements (>180-200
ml/kg/yr) packed RBC

BONE MARROW
TRANSPLANTATION
BEST METHOD FOR CURE
Risk factors:
Hepatomegaly >2cm
Portal fibrosis
Iron overload
Older age

OTHER SUPPORTIVE
MEASURES
Tea thebaine and tannins chelate iron
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, Lthyroxine
Treatment of CCF

IRON OVERLOAD
ASSESSMENT
S. Ferritin
Urinary Fe excretion
Liver biopsy
Chemical analysis of tissue Fe
Endomyocardial biopsies
Myocardial MRI indexes
Ventricular function ECHO, ECG

CHELATION THERAPY
DESFERRIOXAMINE

( 1 unit of blood contains 250 mg iron)

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: DESFERRIOXAMINE

Cardiotoxicity arrythmias
Eyes - cataract
Ears - sensorimotor hearing loss
Bone dysplasia-growth retardation
Rapid infusion- histamine related
reaction- hypotension, erythema,
pruritis
Infection, sepsis

CHELATION THERAPYDEFERIPRONE
Oral chelator - > 2yrs old Dose: 50-100mg/kg/day
Adverse effects:
Reversible arthropathy
Drug induced lupus
Agranulocytosis
Other oral chelators
Deferrothiocine, Deferasirox
Pyridoxine hydrazine
ICL-670 removes Fe from myocardial cells

Prognosis:
Life expectancy: 15-25 yrs
Untreated: < 5 yrs

Thank you
^+++^