1.

Missed out
a) consanguinity
b) on thyroxine ?

Paeds

C/C : Patient, 12 yo, regular blood transfusion 11 years, s/c desfuroxamine 1 year for the underlying
beta thals major, sister with beta thals major as well.
2 fingers hepatomegaly, hyperpigmented skins, stunted growth below 3rd centile.

Discussion :
1) Common fatal infection regarding beta thals major
Answer :

Complication from blood transfusion : Hypotension, anaphylactic shock, bronchospasm

Complications from iron overload : Cardiac siderosis ( CCF, cardiomyopathy )
Complications from iron chelation therapy : Yersinia due to iron chelation （ abd pain, fever,
diarrhea ）
Complications of splenectomy : Requires monitoring in ICU if infections

2) Why given desferrioxamine (Desferal) DFO , complications ?

MOA :
- it picks up from cells & bring it out to the urine and stool and prevents the iron that is stored in body
from interfering with its normal fx.
- serum ferritin level is the best guide for whether the tx is working.
When to start :
- usually when the child is > 2-3 years old when serum ferritin reaches 1000ug/L.
- This is usually occurs after 10 – 20 blood transfusions ( 250 ml pack rbc/ 1 unit of blood = contain 0.2 g
iron )
- In early stage, extra iron is stored in the liver (max 20 g), when the storage is full, then iron is
accumulated in other organs, damaging the organs.
* Normal ferritin level = 100-400 ug/L
Dosage and route :
- average daily dose is 20-40 mg/kg/day, by s/c continuous infusion using a portable pump over 8-10
hours daily, 5-7 nights a week.

3) Why need endocrine referral ? which hormone ? why growth hormone ? incidence of growth
hormone deficiency in beta thals major in malaysia ? patient need gonadotrophin hormone injection at
12 year old ?
4) Management if you are a GP ?
5) Blood transfusion complication, what is hypersplenism and its tx?
Answer :

Iron deposition - Cardiac siderosis ( cardiomyopathy )

- Liver ( cirrhosis )
- Pancreas ( DM )
 - Endocrine glands ( hemosiderosis in pituitary
gland causing infertility )
- Skin ( hyperpigmentation )
Antibody formation - Red cell antibodies
- HLA ab
- Urticaria or anaphylactic shock
Infections - Hepatitis C & B, HIV, CMV, Syphilis, Malaria
Other ( complications from massive BT ) - Fluid overload
- Hypothermia
- Thrombocytopenia (leads to bleeding)
-

6) Other ways to detecting beta-thalas beside fetus hb electrophoresis, complication of villous

sampling ?
7) How to do genetic counseling, percentage of pass down beta thalas gene, what is beta thalas ?
8) Complications of chronic iron overload in Thalassaemia major over 10 years.
Answer :

Endocrine - Growth retardation

- Impaired glucose tolerance ( DM )
- Pubertal delay
- Hypothyroidism
- Hypoparathyroidism
Hepatic - Liver cirrhosis ( especially if with Hepatitis B/C infection )
Cardiac - Arrhythmias
- Pericarditis
- Cardiac failure

Paeds

C/C : 3yo girl currently no complaint, never admitted to the ward, no significant medical condition, no
complications develop.

Discussion:
1) mode inheritance
2) carrier rate in Malaysia
3) possibilities for inconsanguinous couple to have baby of thalassaemia
4) summarise the PE finding and dysmorphic features that we need to look for

General inspection Slate gray hyperpigmentation of skin

Short Stature ( hypopituitarism ), failure to thrive or retarded growth, delayed
puberty
Hands Palmar pallor
Finger clubbing ( CLD )
Face Pallor (anaemia)
Jaundice ( due to hypersplenism, increase RBC destruction )
 Frontal bossing
Maxillary overgrowth
Prominent malar eminence ( hypoxia – bone marrow expand inside the bone 
bone weak and alter shape  make more and more non-functional RBC  RBC
dies easily )
CVS Gallop rhythm
Cardiomegaly
GI Hepatosplenomegaly( d/t resumption of hematopoiesis  extramedullary
hematopoiesis )
Subcutanoeus insulin mark
Desferrioxamine infusion pump
Secondary sex Pubic hair
charactistic Axillary hair
Size of testis
Size of breast

Target volume = (Post Hb-Pre Hb) x Weight x 4.5

5) signs of extramedullary haematopoiesis

6) why in this patient has no splenomegaly
7) how to elicit splenomegaly
8) why spleen move down when inspiration

9) what ix ?
10) PBF what features
Target cells, poikilocytosis, hypochromic and microcytic
11) Hb electrophoresis ? In normal patient ? In thal ?
12) HbF percentage ?
13) Management
14) Why rash after blood transfusion ?
Suspect an acute transfusion reaction if your patient has :
a) sudden rise in temperature > 1 celcius
b) rigors
c) sudden feel unwell in anyway
d) rash
There are 5 type of acute blood transfusion reactions :

15) What do we do if blood transfused is not matched to the donor? What medication to give ?
16) Draw a oxygen dissociation curve
17) What should we anticipate in the bone marrow transplantation ? ( I said graft smtg )
Classification of patient into Pesaro risk groups based on the presence of 3 risk factors
18) What is basophilic stippling ?
denatured RNA found in the RBCs, indicated accelerated erythropoiesis or defective Hb synthesis. Seen
in lead poisoning, megaloblastic anaemia, myelodysplasia, liver disease, haemoglobinopathy, eg:
thalassaemia.
19) The main aim of transfusion are :
to correct the anaemia
to inhibit the expansion of bone marrow ( suppress extramedullary haemopoiesis )
20) Guidelines for transfusion :

Transfusions target :
Paeds

C/C : Abdominal discomfort

HOPI : 16 yo boy presented with intermittent abd discomfort and mild scleral jaundice. Was
diagnosed with thalassaemia a 13 yo and need monthly blood transfusion. Has previous hx of
intermittent fever, pale and jaundice and diagnosed with G6PD deficiency. Other sx were normal.
PE: hepatosplenomegaly, scleral jaundice, delayed puberty(pubic hair stage 1, penis stage 2). Height
and weight equivalent to 50th centile of 11 yo boy.
Diagnosis : Thalassaemia minor or intermedia, with delayed puberty

Discussion :
1) Pathophysiology of G6PD
2) Pathophysiology of thalassaemia
3) Diagnose type of thalassaemia from history alone
4) Examination of blood transfusion complications
5) Assess severity of anaemia
6) Pubertal stage
7) Investigation

Paeds

HOPI : 8 yo Malay girl who was dx with this when she was 1 yo 5 mo. Currently, no active compliant.
Increase frequency of transfusion recently. Serum ferritin: 500, not yet on iron chelating agent. No
other side effect of transfusion or infection.
PE : Demonstrate palpation on splenomegaly. Demonstrate her growth on anthropometric chart.
Diagnosis : HB H Constant Spring

Discussion :
1) When to start ICA? How? Dosage ? What is the side effects of iron overloading?
2) What is the cure for thal patient other than Bone Marrow transplant
3) What is HbH Constant Spring?
Severe subset of HbH – life-threatening severe anaemia
4) What other investigations for the patient ?
Paeds

HOPI : 17 yo Malay male, known case of thal major since 2 year old, regular BT, desferal, vit. C, also on
testosterone and thyroxine.

Discussion :
1) How you want to ask about effort tolerance in this patient ?
2) PE: assess growth, patient is short, how you know?
Assess thyroid fx, secondary sex characteristic
3) Explain about finding in Hb electrophoresis
4) What is the mode of inheritance for thal.

Paeds

HOPI : A 20 yo gentleman( he looks 10-20 yo), known case of beta- thalassaemia major diagnosed at
19 year old ago, on monthly transfusion, s/c desfurrioxamine, no active chief complaint. Strong family
history of B-thal. He was diagnosed when he presented with pallor, lethargy(no jaundice) 7 months
old. He is hospitalized 5 days for transfusion.
Diagnosis : Beta-thal major complicated with hypopituitarism with non-complicancy to s/c desf.

Discussion :
1) What do you think about the complexion of patient( darker ). What it is called ?
Hamatochromatosis
2) Why did the patient did echo?
3) Patient pre-transfusion level : 5g/dl, are you happy with that?
4) So, what is the normal pre-transfusion level?
5) What is hypertransfusion and what is the level? Why hypertransfuse the patient ?
6) If he is presented to you when he was 7 months old, how do you diagnosed?
FBC : anaemia, hypochromic microcytic anaemia
PBF : look for what ?
7) What is the ddx pertaining to this kind of picture?
8) Do you know how to differentiate it? （ MCV/RBC , cut off point is 15 ）
9) What else ?
HB electrophoresis
Baseline serum iron, ferritin, LFT

Paeds

HOPI : 12 yo Chinese girl with no active chief complain. Diagnosed with thalassamia in UMMC after
presented with abdominal distention (splenomegaly), pallor and inactive. Blood investigation (most
probably PBF) was done and she was diagnosed with Beta-Thalassaemia Major. All family members
were screened too and parents was found to be carriers. Other siblings are normal. She was started
on folic acid and regular blood transfusion (once a month). Started in Desferal 6 years ago after her
serum ferritin level was 6000++. Currently she was also on calcium gluconate and vitamin D. She had
her follow-up every 6 months (serum ferritin, echocardiogram, bone age, anthropometric chart, etc.).
Have not attained menarche. Systemic review was normal.
 PE : she was pale and thin. She has maxillary prominence and her jaw was protruded.

Discussion :
1) If a patient presented to you with the initial symptoms like this child, what are your differential
diagnosis (he wanted me to say spherocytosis but I said malignancies)
2) How do you diagnosed this patient? What do you expect to find in her PBF?
3) Why was she started on Desferal?
4) What are the things that you should do before commencing blood transfusion?
5) What are the target for your blood transfusion? Pre-/post-transfusion Hb level.
6) What are the complications from iron overload? Which organ would be involved?
7) Tell me about other hormones that helps in child growth.
8) “Okay, let’s see your patient.” Tell me your findings. He asked about growth and I showed him growth
chart. He asked whether its normal or not if its on the 10th centile? And asked me what else I would like
to do? I said I have already checked for pubertal delay. What are the staging that you used? Which stage
is she in? Should you be worried that she has not attained menarche?
9) What do you do in her follow-up? How often is the follow-up?
Tanner staging
10) What do you do if the iron is exceedingly high? I said splenectomy but apparently they don’t do
splenectomy here anymore.
Increase the dosage of iron chelating agent.
11) What else would you want to offer the patient/family? I said genetic counseling and he asked me
what are the things that you should include in genetic counseling?
12) What do you expect to find on Hb electrophoresis?
13) What are the complications that you get if iron is deposited on the heart? What are the symptoms?
14) Was she adviced on any special diet? I confessed to him that I forgot to asked about the dietary
history and he said its okay.
15) If you are working in the periphery and someone came in with this picture, what would you do? I
said blood examination and things like that. If patient has leukaemia what are your findings on PBF?
Auer rods – AML
Monoblast / Myeloblasts
16) If you screened for carriers in the family, what are your findings on FBC?
Diagnosis of Thalassaemia involves both clinical and laboratory diagnosis :
Laboratory diagnosis involves screening tests and diagnostic tests:
a) Screening test :
- MCH (< 27pg) & MCV (<80fl) *MCH preferable as it is less susceptible to storage changes ( But Hb H
Constant Spring have normal MCV and MCH )
- RDW (normal in thal trait, increased in iron-deficiency CV>14%, thal-intermedia, thal major)
b) Diagnostic test :
- High performance liquid chromatography (HPLC)
- Hb electrophoresis
- Low serum ferritin (alpha-thal is considered when iron-deficiency is excluded & HbA2 is normal)
MCH level

Medicine
C/C : 24y/o malay lady, first time came for exam, with underlying HbE Thal Beta intermedia.
 HOPI :
- Diagnosed since 6y/o after episode of abdo pain.
- Both of parents and 2 older siblings also undergo same test, her Mother- thal B carrier; Father-Hb A?
or HbE? She said HbA at first, then change her answer to HbE. Multiple blood transfusion because of
low hb-every month, Then only need blood transfusion if Hb fall below 7. Usually pre blood
transfusion is also below 7 -dt the splenomegaly . post transfusion: 14-15, usually 2-3 packs
transfused at once, which stands for couple of months before she needed to be transfused again.
BOTH of siblings also carrier, while she has both of her parents genotype- thus HbE.
PMHx (try ask for their record book)
- Splenectomy when she was 14y/0
- Started desferrioxamine about 11 month before the splenectomy . 5x/week injection, with vit.c and
folic acid supplement.
- Compliance to med and f/up
- Multiple admission last year dt tonsillitis, ear infxn, and PUO which was found later dt left renal
abscess
- Was given immunization prior to splenectomy
PSHx
- Undergo laparoscopic cholecystectomy couple of years ago for cholelithiasis
Drug Hx
- on thyroxine after that, and couple of years
- on oral aspirin dt high platelet count
FMHx
- Father has passed away dt multiple medical problem- IHD, HPT, stroke
- Mother is a housewife
SHx
Not married, no bf
Lives with family at PJ
Admin at insurance company, diploma in insurance
Normal academic achievement
Dietary Hx
no specific restriction
PE: Mild palmar and conjunctival pallor. Multiple scar on abdomen- 4 lap cholecystectomy scar, 1
splenectomy scar ( transverse on the left upper abdo region, multiple hyperpigmented scar dt
desferrioxamine injxn, and one small scar from percutaneous drainage of Left renal abscess at the left
back. Liver enlarged 3-4 finger breadth below the right subcostal margin, firm, smooth surface, well
define margin-liver shape, dull on percussion.

Discussion :
1) Why do you think patient had multiple admissions？
Answer: Patient has undergo splenectomy, so prone to get infection.
2) What is the function of the spleen ?
Answer : filter the blood, immunity, and extramedullary haematopoiesis
3) What do u think about the affinity of oxygen in thalssemia patient compare to normal person?
Answer : High affinity
4) How do u manage this patient?
During the f/up screening for the complication of thalassemia endocrinopathies
a) hypopituitarism- which can cause thyroid problem which patient already has- TFT on
f/up.
b) hypogonadism , but patient already attained menarche at 15y/o
c) Liver function test at least 2x yearly, dt iron deposition which can lead to CLD
d) Echo for cardiomyopahty- at least yearly.
e) Blood glucose screening for secondary DM dt iron deposition
For non-pharmacological mx
a) advice patient on reduce the intake of high iron food such as meat and spinach vege.
b) eat the vit.c folic acid, and increase intake of tea as it can help to excrete the excess iron.( remember
to ask *****)
c) screening for desferral side effect, but patient only has local skin side effect, and no abnormality on
fundoscopy.
d) B-thal support grp
5) What do they give before splenectomy?
Answer : Immunization such as pneumococcal vaccine and Hib vaccine
6) Why patient given aspirin ?
Answer : Because of the high platelet count(thrombocytosis) whick will put the patient at risk of
thrombosis, stroke.
Prof tan: what happen when there’s splenomegaly?
Me: it causes hypersplenism lead to pancytopenia
Prof alizan kind of trick me later ….about the pancytopenia,
he ask what blood component which reduce in splenomegaly . all can be
reduce
la, I already answer earlier, donno what he want. Pening2
Prof tan: if patient want to get married, what is your
advice?
Me: I will refer her to genetician
What do u want to advice the patient
Me: I will advice patient to bring her bf/future husband for
thal screening because if her bf has thal too then their future children
will be at risk of having thal major, and possibly hydrops fetalis, eyh no no,
not hydrops, only thal major and carrier (=.- aiya)
Prof alizan : eyh? No hydrops?
Me : because hydrops is dt thal alpha major
Prof alizan : still can ( cant remember actuly what he told
me, but I donno the answer though)
They did ask how many can be carrier and some other, cant
remember the detail of Q
I just answer all of them can be carrier, with at least one
thal major.

Obs
Aidee ikram Examiner:-prof jamiyah(main),prof zuraini, external examiner paeds
Specialty:-ONG 28/M/lady/G2P1 currently at 28 week POG k/c/o beta thalassemia minor diagnosed 2009 during
her 1st pregnancy came in for exam purpose with no active chief complaint. Diagnose beta thalassemia minor
during 1st booking of her previous pregnancy thru blood investigation. Patient had syncopal episode associated
with lethargy and giddiness a few week later after diagnosed with beta thalassemia. She was told Hb low but
unaware of the value. Patient was well after given iron tablet medication and no blood transfusion given. Patient
had family history of beta thalassemia as both her sister was diagnosed with it also during pregnancy. Husband
also a beta thalassemia carrier only know this year eventhough the test had been done during 1st pregnancy.hi
Currently, patient was well with no active complaint. She had no symptom of anemia such as
giddiness,lethargy,palpitation and shortness of breath. She also did not on any medication or blood transfusion.
Normal clerking pregnancy -antenatal uneventful PE:-slight conjunctivae pallor -pfennenstial scar
Question:-what kind of diagnostic test for beta thalassemia pt received during previous pregnancy?=Hb
electrophoresis
-do we usually do that test for all normal pregnant women?-no.but in this case,probably they found out that
patient had microcytic hypochromic anemia in FBC and thallasemic picture in PBF which the decided to do Hb
electrophoresis. Beside,she had family history -blood transfusion?do u think patient need that..no.patient is beta
thalassemia minor.no need transfusion -did the husband also a carrier?-oh yes. -why did I emphasize on that?-it is
important in term of planning for future pregnancy and baby -bring to patient:-what sign u would like to
elicit?show me?-conjunctiva pallor je la -do abdominal exmntion -show me how u elicit scar tenderness? -what is
beta thallasemia?how many type?-minor,intermedia,major -what ix u wanna do in this pt?fbc,fetal monitoring -
what mx u would like to do starting from now?-as normal pregnant:-serial f/up with monitoring -consider monitor
Hb -plan MOD (admit @ 38week bcause of risk) -counselling for future pregnancy -what do u think pt Hb?-around
9-10 -if that happen,do u consider given iron?yes. -what kind of iron?dose?ferrous fumarate(forget dose) -what do
u think of MOD?-ELSCS.why?because of risk pt had(previous scar,b-thal) -why risk previous scar?-uterine
rupture..how many percent?-1%..what is successful rate VBAC?-70-80% -how do u counsel pt after this?-talk about
risk of getting thalassmic baby?thal-25% normal-25% -plan future pregnancy -contraception(if needed) Personal
thought:-prof jamaiyah superb gila ba nice..give u a lot of hint and prompt..hope u all do well n pass together..gud
luck
Guidelines for management of presumed or proven infection in TDT patients

Low Threshold For Hospitalisation

Early and Prompt Assessment

Focus on abdominal, sino-pulmonary and skin-soft tissue foci/
Absence of fever in an unwell patient does not exclude
infection

Unwell and surgical Well child with reliable

asplenia caregiver

FBC, Urea/Lytes, LFT,

FBC & Blood culture
CRP
Blood Culture
Urine FEME& culture
Abdominal X ray
- Home with advice
CXR
- Oral abx (e.g co-
Amoxiclav)
- Ambulatory review in
2-3 days

- Broad spectrum antimicrobial therapy with anti-Klebsiella activity (Eg:

IV Ceftriaxone 75mg/kg daily ).
- Withhold desferrioxamine (DFO) and Deferiprone (DFP).
- Fluid resuscitation and red cells transfusion as indicated
- Administer stress dose corticosteroid (hydrocortisone :
100mg/m2/dose)
- Blood glucose monitoring (potential for unmasked glucose intolerance)
- Anticipate decompensated cardiac function (anaemia, myocardial
siderosis)

Patient with TDT Dependent Thalassaemia are susceptible to severe infections.

Infections is the second most important cause of mortality in patient with TDT.
Contributory factors: hepatic iron overload, DFO use (including injection site infection), craniofacial
abnormalities, calculous cholecystitis, surgical asplenia & agranulocytosis (DFP use)