Case Presentation

BY
DR. ZAHRA JABEEN
FCPS II RESIDENT (PAEDS UNIT II )
ABBASI SHAHEED HOSPITAL
10.5 month old female child weight 6.3 kg unvaccinated resident of New Karachi comes in E.R with
the complaint of :
 Yellowish discoloration of skin and pallor for two weeks
 Fever & cough for one week
According to the mother child was in her usual state of health two weeks back then mother noticed
yellowish discoloration of skin first evident on face and sclera then gradually became generalized
(from head to the sole of foot) It was associated with pallor, decreased appetite and pale stool and
dark urine. She also gradually developed fever low in grade (undocumented) intermittent in
nature,relieved on taking anti-pyeritics with no aggravating factor it was associated with cough
which was non productive mild in severity, persistent through out the day with no diurnal variation.
There is no history of melena or bleeding.
Past Medical History

 First episode of pallor

 She developed first episode of pallor at the age of three months for which they
went for Dum/Darood
 Second episode :
 She developed 2nd episode of pallor at the age of six months got admitted in near
by hospital at Nagan for three days where she transfused with PCV , no workup
done.
Third Episode
She developed 3rd episode of pallor at the age of eight months got admitted for thirteen days in civil
hospital where she was transfused with PCV, workup done.

Past surgical history :

Non significant

Transfusion hx:
she was transfused two times with pcv, no allergy or reaction reported
Birth History
Anti-Natal: It was a booked case. Mother was transfused with IV iron during her pregnancy (seven
month of gestation)
Natal:
It was NVD at term by a nurse at near by clinic no history of any complication
Post Natal:
Immediately cry after birth with normal weight no history of jaundice, fits, cyanosis no history of
NICU admission
Nutritional History:
She was exclusively breast fed till 4th month of life weaning started at 4th month but patient was not
taking properly any food. Before the on set of disease she was on breast feed and lactogen-II with
inadequate dilution (2 Oz) thrice a day and occasionally taken one to two biscuits banana, cerelac
and khichri but not regularly.
 Calories required = 900 kCal ( PCM grade II)
 Calories in take = 600 kCal
Immunization History:
Unvaccinated

Development History:
 Social Smile = 1.5 months
 Neck Holding = 3 months
 Roll Over = 6 months
 Sitting without support = 9 months (up to the mile stone )
Family history:
 She is the forth product of consanguineous marriage
 No deaths or still birth / miscarriages
 Mother is mildly anemic
 First cousin has been transfused multiple times with PCV now he is three years old and he still
got transfusion.
 No history of TB, DM in the family
Socio Economic History:
Ten family member lives in a house of two rooms, there is only two bread earner they drink tap water.

Examination:
10.5 month old female child with 6.3 kg irritable lying on a mother’s lap with vitals of;
 HR 130 BPM
 RR 60/min
 Temp 100 F
 BP 80/60 ( 75th centiles)
 PO2 90 % at room air, 98% at nasal prongs
 A+++ , J+++ , D- ,E- ,CL- ,CY- ,LN- (patient is severely pallor and yellowish from head to sole of the foot )
Anthropometric Measurements:
 Length = 73 cm b/w 50th and 75th centiles
 FOC 47 cm above 95th centiles
 Weight 6.3 kg below 5th centiles
Respiratory:
Inspection
No scar mark, swelling or rash. Normal movement of chest

Palpation
No tenderness or swelling

Percussion
Resonant percussion
Auscultation
Bilateral equal entry of air with b/L mild crepts.

CVS:
 S1+0 +S2 , no murmur was appreciated.
Abdomen:
Inspection
 normal shape and size with centrally placed umbilicus no prominent vein or scar mark present.
Palpation
 Soft, Non tender
 Liver = 4 cm palpable smooth regular margins soft in consistency.
 Span: 8.5 cm
 Spleen = 3 cm palpable with smooth regular margins
Percussion
No fluid thrill or shifting dullness.
Auscultation
 Normal bowel sound was present
 No bruit heard
Genitalia
 normal
CNS
Upper Limb Lower Limb
 Bulk Normal Normal
 Power Normal Normal
 Tone Normal Normal
 Reflexes Normal Normal
 Clonus - Absent

Sensory SYS : Intact

 No sigh of meningeal irritation

Differentials:

 Hemolytic Anemia with PCM grade II

 Malaria with PCM grade II
 AutoimmuneHepatitis with PCM grade II
Investigations:
 CBC with peripheral film
 Retic count
 Hb electrophoresis
 LFT
 Blood CS
 MPICT
 CXR
 Ultrasound Abdomen
 Osmotic fragility
Investigations:
CBC
 HB = 3.1
 HCT = 11.7
 MCV = 67
 MCH = 29
 MCHC = 33
 TLC = 16.1
 Neutrophils = 65
 Lymphocytes = 50
 Eosinophils = 3
 Monocytes = 3
 Basophils = 0
 Platelet Count = 170 x10^9
 Retic Count = 5.5
 RDW= 34.5%
Peripheral Film
Microcytic, Anisocytosis, Hypochromic, Tear drop cells
Hb Electrophoresis
 HbA = 67.9 (Ref Range 96-98 %)
 HbF = 29.3 (Ref Range 0.2-1 %)
 HbA2 = 2.8 (Ref Range 2-3.5 %)

Osmotic Fragility:
-ve for HS
 LFT:
 Bilirubin (Total ) = 17.1
 Bilirubin (direct ) = 11.3
 Gamma GT = 42
 Alp = 373
 SGPT = 35

Blood CS
No growth
MPICT:
 -ve

Ultrasound Abdomen:
 Hepatosplenomegaly
 Liver = 9.8 cm
 Spleen = 6.5 cm
Treatment:
 Transfused with PCV (twice)
 Inj Fortum 320 mg IV 8H (diluted in 30 CC NS) (100 mg/kg/day BD)
 Nebs with 2 CC NS 8H
Final Diagnosis:
 Thalassemia with PCM grade-II
Thalassemia:
INTRODUCTION
 Thalassemia is an inherited autosomal recessive blood disorder
 It results in excessive destruction of red blood cells and further leads to anemia.
 It is caused by variant or missing genes that affect how the body make
hemoglobin.
 People with thalassemia make less hemoglobin and fewer circulating red blood
cells than normal, result in mild or severe anemia
Types:

 Alpha Thalassemia
 Beta Thalassemia
Alpha Thalassemia:
 Alpha thalassemia is the result of changes in the genes for the alpha globin
component in hemoglobin.
 Silent carrier: deletion of only one gene, no sign or symptoms present.
 Alpha thalassemia trait:
- deletion of two genes
 Common in African American and those of Mediterranean descent.
 Mild hypochromic , microcytic anemia without clinical problems.
 Often diagnosed as iron deficiency anemia, need molecular analysis for diagnosis.
 HgB disease:
- deletion of 3 genes
 Hgb Barts > 25% in newborn period and easily diagnosed with electrophoresis.
 At least one parent has alpha thalassemia trait, and can be identified electrophoreticaly,
microcytic and hypochromic with mild to moderate anemia; target cells present, mild
Alpha Thalassemia:
 Alpha thalassemia major:
-deletion of 4 genes ; severe fetal anemia resulting in hydrops fetalis.
-New born has predominantly Hgb barts with small amount of other fetal
Hgb; immediately exchange transfusion required for any possibility of survival.
-Transfusion dependent with only chance of cure ( bone marrow
transplant).
Beta thalassemia:
 Beta thalassemia minor (also called beta thalassemia trait): People with beta
thalassemia minor may have mild anemia, but usually don't need any medical
treatment.
 Beta thalassemia intermedia: People with beta thalassemia intermedia have
moderately severe anemia and some will need regular blood transfusions and
other medical treatment. The blood transfusions deliver healthy hemoglobin and
RBCs to the body.
 Beta thalassemia major (also called Cooley's anemia): People with beta
thalassemia major have severe symptoms and life-threatening anemia. They need
regular blood transfusions and other medical treatment.
Pathophysiology:
 Alpha thalassemia results when there is disturbance in production of α-globin from any or all four of the
α-globin genes.
 Genes are responsible for regulating the synthesis and structure of different globins which are divided into
2 clusters.
 The α-globin genes are encoded on chromosome 16 and the γ, δ, and β-globin genes are encoded on
chromosome 11
 A normal person carries a linked pair of alpha globin genes, 2 each from maternal and paternal
chromosome.
 Therefore, alpha thalassemia occurs when there is a disturbance in production of α-globin from any or all
four of the α-globin genes.
 When functional point mutations, frame shift mutations, nonsense mutations, and chain termination
mutations occur within or around the coding sequences of the alpha-globin gene cluster hemoglobin is
impaired. When that occurs, protein synthesis may be inhibited.
Pathophysiology:
 Normal production of alpha chains is absent which results in excess production
of gamma- globin chains in the fetus and newborn or beta- globin chains in
children and adults.
 The β-globin chains are capable of forming soluble tetramers (beta-4, or
HbH).This form of hemoglobin is still unstable and precipitates within the cell,
forming insoluble inclusions called Heinz bodies
 These Heinz bodies damage the red blood cells. This further results in damage to
erythrocyte precursors and ineffective erythropoiesis in the bone
marrow,hypochromia and microcytosis of circulating red blood cells.
 In beta thalassemia , alpha globin chain are in excess to non alpha globin chains,
and alpha globin tetramers(alpha4) are formed and appear as RBC inclusions.
The free precursors damage the RBC membrane and shortens RBC survival
leading to anemia and increased erythroid production.
Sign and Symptoms:
 Anemia
 Pale skin
 Weakness
 Fatigue
 Enlarged liver and spleen- hepatosplenomegaly
 Dark urine
 Abnormal facial bones and poor growth
 A poor appetite.
 Adolescents with the severe form of beta thalassemia may experience delayed
puberty.
Sign and Symptoms:
 People with thalassemia major or intermedia usually have a buildup of iron in the
body, either from the disease itself or from the repeated blood transfusions.
Excess iron can damage the heart, liver, and endocrine system.
 Hb Bart syndrome can cause complications in pregnancy such as;
 High blood pressure
 Premature delivery
 Abnormal bleeding
 Jaundice
Clinical Manifestations:
 In thalassemia major, patients have severe anemia, ineffective erythropoiesis,
extramedullary hematopoiesis, and iron overload resulting from transfusion and
increased iron absorption.
 The classical presentation of children with severe disease includes thalassemic
facies (Maxilla Hyperplasia, flat nasal bridge, frontal bossing)
 The skin may show pallor from anemia and jaundice from hyperbilirubinemia.
 The skull and other bones may be deformed secondary to erythroid hyperplasia
with intramedullary expansion and cortical bone thinning.
Clinical Manifestations:
 Heart examination may reveal findings of cardiac failure and arrhythmia, related
to either severe anemia or iron overload.

 Abdominal examination may reveal changes in the liver, gallbladder, and spleen.

 Patients who have received blood transfusions may have hepatomegaly or

chronic hepatitis due to iron overload.

 The gallbladder may contain bilirubin stones formed as a result of the patient's
lifelong hemolytic state.
Clinical Manifestations:
 Splenomegaly typically is observed as part of the extramedullary hematopoiesis
or as a hypertrophic response related to the extravascular hemolysis.

 In addition to cardiac dysfunction, hepatomegaly, and hepatitis, iron overload can

also cause endocrine dysfunction, especially affecting the pancreas, testes, and
thyroid.

 Transfusion-associated viral hepatitis resulting in cirrhosis or portal hypertension

also may be seen.
Treatment:
 Transfusion Therapy: transfusion should be given at intervals of 3 to 4 weeks
with the goal being to maintain a pretransfusion Hb level 9.5 to 10.5 g/dl
 Iron overload monitoring with serial ferritin level, however magnetic resonance
imaging are standard noninvasive methods to measure tissue iron overload.
 Chelation Therapy: It starts generally after 1 year of transfusion therapy and
correlates with the serum ferritin>1000ng/ml and/or liver iron conc> 5000ug/g
dry weight. It is not currently used in children less than 2 years.
 Deferoxamine
 Deferasirox
 Deferiprone
Treatment:
 Hydroxyurea: A DNA metabolite increases HbF production, mainly used in
thalassemia intermedia.

 Hematopoietic Stem Cell Transfusion: It results in 90% survival and 80%

event free survival in HLA matched candidates.

 Splenectomy: decrease transfusion requirements.

Preventive and Monitoring of Thalassemia
Patient:
 Cardiac Disease
Cardiac disease is the major cause of deaths in thalassemia. Serial echocardiograms
should be monitored to evaluate cardiac function and pulmonary artery pressures.
 Endocrine Diseases
Endocrine function progressively declines with age secondary to hemosiderosis and
nutritional deficiencies.
 Psychosocial Support
Thank You 