Short and long case approach tp anemia with abdominal distension

1. Approach to child with anemia with
abdominal distension
Dr Varsha Atul Shah
senior Consultant
Singapore General Hospital

2. Approach to child with anemia with
abdominal distension
Lead can be:
1. This 7-year-old girl was referred from Malaysian colleagues for further follow up
and management. Please examine her abdominal system.
 8 years old boy of consanguineous parents presented with complaints of not
growing well, gradual pallor & abdominal distension for 4 years. On examination
he was severely pale; facial dysmorphism & hepatosplenomegaly were present. He
had history of repeated blood transfusion.
2. Siti is a 7-year-old Indonesian girl, was brought by his parents from Batam, when
she was 1 year old.
At the age of 3, Siti was in the 10th percentile for height and weight, pale, and his
hemoglobin was 5.8 g/dL. Following further diagnostic studies, she was diagnosed
with beta-thalassemia major. Over the course of the next 4 years, Siti was
hospitalized every 1–2 months so she could be transfused with packed red blood cells.

3. Thalassemia family

4. Thal facies

7.  major remain asymptomatic until 3-6 month

10. Mentzer Index
 Used to differentiate iron deficiency anemia from beta thalassemia.
Mentzer index = MCV/RBC count in millions
 If, >13 – iron deficiency anemia is more likely
 <13 – beta thalassemia is more likely

19. Investigations
 FBC & smear: Hb: 8 g/dl, ↓↓ MCV & MCH, Reticulocyte count ↑
(upto 5-8%)
 Leucocytosis, hypochromic microcytic anaemia, with nucleated
RBC & reticulocytopenia
Poikilocytosis-Variation in cell size
Anisocytosis-Variation in cell shape
Normoblasts-Nucleated red cells
 LFT: Elevated unconjugated bilirubin.
 Haemoglobin electrophoresis: Hb A is either markedly decreased
or totally absent. Of the total haemoglobin concentration, 30%
to 90% is Hb F.
 BM: hyperplasia is seen in bone XR.
 Iron study: elevated S. ferritin & transferrin saturation.

20. X-ray-not done routinely
Skull:
 Thinning of outer table of skull
 Absence of normal trabeculation
 Hair-on-end appearance
 Due to widening of the diploic spaces
Maxilla: Maxillary overbite and prominence of the upper
incisors
Phalanges:
 Rectangular shape
 ↑ Trabeculation
 Thinning of cortex (small bones)
 Expansion of medullary cavity

22.  "Thalassemia" is a Greek term “Thalassa”, which means "the sea"
 “Emia” means "related to blood.“
 Was called "Mediterranean anemia" was first described in people of
Mediterranean ethnicities.
 History in 1925 Prof. Thomas Benton Cooley observed in some children that
severe anemia combined with massive hepatosplenomegaly, bone deformities
and severe growth retardation.
 He named this disorder "erythroblastic anemia," but it became popularly
known as Cooley's anemia.
 The word thalassemia was first used in 1932

27. Case Study
During a routine follow-up visit at the
hematology clinic, F laboratory results
were as follows:
Hemoglobin: 10 mg/dL
Total serum iron: 150 microg/L
The hematologist discusses the planned
treatment with Siti and her
parents.

28. Frontal and cheek bossing
saddle nose
maxillary protrusion (chipmunk face)
malocclusion.
inadequate lip seal
anterior overbite
Chronic sinusitis
Hearing loss

31. - Frontal and cheek bossing
- saddle nose
- maxillary protrusion (chipmunk
face)
- malocclusion.
- inadequate lip seal
- anterior overbite
- Chronic sinusitis
- Hearing loss

33. Increased spaces,
overbite and
malocclusion of teeth
Frontal bossing

36. Xray Skull:
-expansion of the erythroid marrow widens the marrow
spaces, thinning the cortex and causing osteoporosis
- the classic "hair on end" appearance of the skull results
from widening of the diploic spaces
-maxilla may overgrow, which results in maxillary
overbite, prominence of the upper incisors, and
separation of the orbit. –
Xray of long bones: a lacy trabecular pattern with
osteopenia and osteoporosis

40. 1. Discuss the significance of Siti’s family’s
geographical background to her diagnosis.
2. What is beta-thalassemia, its incidence, and
etiology?
3. Discuss the clinical manifestations of beta-
thalassemia.
4. Discuss the significance of Siti’s laboratory
values.
5. Discuss the complications associated with the
chronic blood transfusions associated with Adriana’s
condition.
6. Discuss the standards of care once Adriana reaches the
parameters
prescribed for annual packed red blood cell transfusions
and how they affect the child’s need for future blood
transfusions.
7. What are the priorities of care for Siti?
8. Siti is diagnosed with hemosiderosis. What is
hemosiderosis and how is it treated?
9. Siti is prescribed an initial dose of
deferoxamine mesylate 1 g IM and 400 mg
SC each day for 5 days. Siti’s weighs
15 kg (33 lb). Would the nurse question
this prescription?
10. Discuss the options available for
Siti to prevent lifelong blood
transfusions.

42. 1. Discuss the significance of Siti’s family’s geographical background to her
diagnosis.
 Beta-thalassemia is an autosomal recessive genetic
disorder affecting hemoglobin chains and has its highest
incidence in children of Mediterranean descent.
 Thalassemia is the most common autosomal recessive
condition in Singapore.
 The gene prevalence of Thalassemia in our local
population is approximately 3% carrier rate in Singapore
 In Singapore, the prevalence of beta thalassaemia (β-
thalassaemia) trait is 0.9% and haemoglobin E (HbE) trait
is 0.55% .
 Malay population accounts for 74% of the registered
subjects with Hb E/β-thalassamia

43. 2: What is beta-thalassemia, its incidence, and
etiology?
Normally the hemoglobin is made up of globin
chains (Hb- and Hb-)
In beta thalassemia the beta chains of the
molecule of the hemoglobin are missing.
This results in deficient hemoglobin and the
development of fragile, microcytic,
hypochromic erythrocytes.
These erythrocytes are unable to carry
adequate oxygen to the cells and tissue,
leading to inadequate tissue perfusion and
delayed growth and development.

44. Thalassemia minor: thalassemia trait, lacks the
beta protein but not sufficiently to interfere
with the normal function Thalassemia
intermedia is a condition
where the lack of beta protein in the
hemoglobin is great enough to cause a
moderately severe anemia and significant
health problems, including bone deformities
and enlargement of the spleen.
The severity of this condition is measured by
the number of blood transfusions the child
requires.

45. Beta thalassemia major:
 most severe form of this disease
 the complete lack of beta protein in the hemoglobin
 life-threatening anemia
 requires regular blood transfusions and extensive
ongoing medical care.
 Enlargement of both liver, spleen and jaundice due
increased hemolysis of the abnormal red blood cells
 bone marrow increases production of erythrocytes for
tissue perfusion causes hyperplasia of the bone marrow
 causes thickening of the bones throughout the body and
delayed development.

46. 3. Discuss the clinical manifestations of beta-
thalassemia.
The clinical manifestations :
Pallor is present because hemoglobin is a major
factor in the normal skin color.
FTT, reaching only the 5th percentile for
growth.
Recurrent severe anemia (hemoglobin 6 g/dL)
and hepatosplenomegaly.
Bones to thicken and become less flexible his
leads to pathological fractures and pain,
chipmunk facies

47. History
 Severe Anaemia
 Thalassaemic facies
 Hepatosplenomegaly
 Growth retardation, etc
 Symptoms of anaemia
 +ve family history
 H/0 blood transfusion
 FTT approach to diagnosis

48. History
 Is there progressive pallor?
 Profound weakness
 Fatigue
 FTT
 Poor appetite, lethargy.
 H/O jaundice
 Time of 1st transfusion
 Gradual abdominal swelling
 Family H/O same kind of illness
 H/O sibling death
 Consanguinity; Leg ulcer etc History

49. 3. Discuss the clinical manifestations of beta-
thalassemia.
Clinical Features ( Thalassemia Major)
Age at presentation : 6-9 month ( Hb F replaced by HbA)
 progressive pallor
 cardiac failure
 Failure to thrive
 gross motor delay
 Feeding problems
 bouts of fever & diarrhoea
 Hepatosplenomegaly

50. 3. Discuss the clinical manifestations of beta-
thalassemia.
Clinical Features ( Thalassemia Major)
By childhood:
Growth retardation
severe anemia
cardiac dialatation
Transfusion dependent
Icterus
Changes in skeletal system

51. Clinical Features ( Thalassemia
Intermedia)
 Age of onset: usually 2-6 years but
 Patient may be symptomless until adult
 Varying degree of pallor,
 Hepato-splenomegaly
 bony change
 Less transfusion dependent
 Longer survival than thalassemia major

52. Clinical Features ( Thalassemia Minor)
 Usually, asymptomatic
 Incidental finding or during family analysis
 May present as Fe deficiency anemia
 Unresponsive/ refractory to iron therapy
 Normal life expectancy

54. 5. Discuss the significance of Siti’s laboratory
values.
Siti is experiencing anemia as indicated
by her hemoglobin level of 10 g/dL;
however, for children with beta-
thalassemia, the goal of treatment is to
maintain hemoglobin levels between 9
and 10 g/dL.
The more disturbing value is her total
serum iron of 150 microg/L.
The normal level of serum iron for
children is 50–120 g/L. Siti’s value
indicates iron toxicity.

58. Discuss the complications associated with the
chronic blood transfusions in Siti’s condition.
The primary complication of
chronic blood transfusions is
elevated iron levels that can
lead to tissue and organ failure.

59. Complications of thalassemia
A. Anaemia
B. Ineffective & excessive erythropoiesis
B. Iron overload due to blood transfusion
C. Chronic hemolysis
D. Hypercoagulable disease
E. Infection
F. Treatment related complications: Side effects of chelation

62. Complications due to blood transfusions
 Acute haemolytic reactions
 Delayed transfusion reaction
 Autoimmune hemolytic anemia
 Febrile transfusion reaction
 Allergic reaction
 Transfusion related acute lung injury (TRALI)
 Graft versus host disease (GVHD)
 Volume overload
 Transfusion of disease – HAV, HBV, HIV,CMV,HCV

63. Infection in Thal Major
 Anaemia
 Iron overload – Yersinia, Klebsiella
 Hypersplenism
 Splenectomy – Pneumococci, Meningococci, Hemophilus influenzae
 Transfusion related – HBV, HCV, HIV etc.

64. Causes of death in thalassemia
 Congestive heart failure
 Arrhythmia
 Sepsis due to increase susceptibility to infection
 Multiple organ failure due to hemochromatosis (commonest cause)

76. Desferroxamin

99. 6.Discuss the standards of care once Siti reaches the parameters prescribed
for annual packed red blood cell transfusions and how they affect the
child’s need for future blood transfusions
The standard of care once Siti reaches the
parameters for annual red blood cell
transfusions is the removal of the spleen.
The spleen enlarges, resulting in increased
hemolysis of red blood cells.
This process increases the risk and
progression of iron toxicity.
A splenectomy results in a lifelong
increased risk for infection, requiring the
use of prophylactic antibiotics.

100. 7. What are the priorities of care for Siti?
1. Ineffective tissue perfusion related to
deficiency of hemoglobin secondary to
disease process
2. Risk for injury, tissue and organ damage
related to elevated serum iron levels
3. Deficient knowledge related to Siti’s
condition, treatment, and home care

101. 8. Siti is diagnosed with hemosiderosis. What is
hemosiderosis and how is it treated?
Hemosiderosis is the term for
elevated serum iron levels.
Occurs as a result of chronic blood
transfusions and is treated with the
use of a chelating agent.
Deferoxamine mesylate is the
agent of choice to reduce serum
iron levels.

102. 9. Siti is prescribed an initial dose of deferoxamine mesylate 1 g IM
and 400 milligrams SC each day for 5 days. Siti’s weighs 18 kg. Would the
nurse question this prescription?
 The normal loading dose of Deferoxamine mesylate is 1 g either intramuscularly or intravenously.
 Maintenance is 20–40 mg/kg per day
 Subcutaneous mini-infusion pump over a period of 8–24 hours.
 Duration of treatment is 5–7 days.
 Siti can receive 300–600 mg of this agent per day, so her dose is safe and although the nurse
would evaluate the prescription based on the 7 rights of medication administration, she would
not question this prescription.

108.  Other options:
 Bone marrow transplantation (BMT) or cord blood
transplantation is indicated to prevent the lifelong need
for blood transfusions.
 BMTs are complicated by the need for the donor to be
genetically matched to the recipient.
 Cord blood transplants are similar to BMTs except the
stem cells are harvested from the placenta or umbilical
cord of a suitable donor.
 The advantage of cord blood transplants is that the
donor does not require as close a genetic match as for
BMT and the probability of rejection is much lower.

109. Management in nutshell
Non-transplant patients:
Regular blood transfusions
Iron-chelation therapy
 Prevent iron overload and organ dysfunction
 Deferoxamine (prolonged SC infusion)
 Deferiprone, Deferasirox (oral)
Lifestyle measures:
 Normal diet
 Folic acid supplementation + small doses of vitamins C & E
 Iron supplements not given.
 Drinking tea with meals
 Decrease iron absorption in gut
Hypersplenism:
 Splenectomy
Hematopoietic stem cell transplantation
 Only known curative treatment for thalassemia

115. Prevention of Thalassemia
1. Identification of carriers
2. Premarital screening
3. Genetic counseling
4. National Thalassemia Registry
Prenatal counselling
1. Preimplant genetic testing
2. Blood sampling from parents
3. Fetal sampling
4. Chorionic villus sampling-11-14/52
5. Amniocentesis-15-20/52
6. Fetal blood sampling- after 18/52
7. HPLC analysis of cord blood

116. Follow only 2 simple steps
Step 1: Get your partner and yourself tested
for thalassemia before marriage.
Step 2: If both your partner and you are
thalassemia minors, consult your doctor for
prenatal diagnostic test.
What test is required to detect Thalassemia
A complete Blood count test
A Hemoglobin HPLC analysis to estimate Hb
A2 levels.

117. Quiz:
Q 1. Which of the following statement is
correct about Thalassemia disease?
A. Thalassemia is caused by mutations in the DNA of cells that make
hemoglobin.
B. The type of thalassemia depends upon the number of mutations in genes.
C. In mild thalassemia you may not need treatment.
D. All the above

118. 2. Which of the following is not the
symptom of Thalassemia disease
A. Slow growth and Weakness
B. Abdominal cramps
C. Dark Urine
D. Facial bone deformities

119. 3. Which type of thalassemia disease is
Cooley anemia?
A. Alpha- thalassemia
B. Beta- thalassemia
C. Alloimmunization
D. None of the above

120. 4. Which blood tests detect if a person is a
carrier of thalassemia?
A. A complete blood count (CBC)
B. A reticulocyte count
C. Prenatal testing
D. All the above

121. 5. Which of the following statement is
correct about alpha-thalassemia?
A. In alpha thalassemia, the hemoglobin does not produce enough alpha protein.
B. The severity of thalassemia depends on how many genes are mutated.
C. Alpha thalassemia is common in southern China, Southeast Asia, India etc.
D. All the above

122. 6.What are the two major types of
thalassemia?
A. Alpha
B. Beta
C. Theta
D. gamma

123. 7.Why is b-thalassemia major usually evident
only 6 months after birth?
A. The fetal Hb persists up to 6 months when fetal hemoglobin (Hb-gamma)
disappears and is replaced by adult Hb.
B. The product of the b-globin pseudogene is highly expressed only after birth.
C. The Hb subunits encoded by the a cluster (which has two copies of the a-
globin gene) are sufficient until after birth.
D. The switch from g-gene to b-gene expression occurs around the time of
birth.
E. The mother's normal red blood cells provide oxygen to the fetus in utero

124. 8.Which type of alpha thalassemia is not
survivable?
A. Silent Carrier
B. Alpha Thalassemia Minor
C. Hydrops Fetalis
D. Hemoglobin H Disease
E. Cooley's Anemia

125. 9.Normal adult haemoglobin (Hb A) consists
of:
A. two α (alpha) and two β (beta) chains.
B. two α and two γ (gamma) chains.
C. two α and two δ (delta) chains.
D. four γ chains.

126. 10.Severe anaemia at birth is a feature of
what?
A. Alpha-thalassaemia
B. Beta-thalassaemia
C. Hereditary persistence of fetal haemoglobin
D. Sickle cell disease