JI Isidro, Denelyn Marice

XX, 59 years old, female, married, Roman

Catholic, government employee, born on June
6, 1952 in Quezon City, seen for the 1st time at
FEU-NRMF OPD March 10, 2011.

Chief

Complaint: body weakness

1 year PTC, pt. experienced easy fatigability assoc.

w/ dizziness, described as spinning in character

no other s/s noted such as, pallor, vomiting, fever,

cough, nor difficulty of breathing

self-medicated with Multivitamins (Pharmaton) 1

cap OD and Betahistine (Serc) 24 mg/tab 1 tab BID
PRN for dizziness which afforded temporary relief

no consultation done

patient was apparently until well.

week prior to consult, the pt. again

experienced easily fatigability and dizziness,

still

no consultation done, but patient

continued to take her Multivitamins and
Betahistine

 2days

prior to consult, still with easy

fatigabilitythe pt. hence decided to
consult in our OPD Department on February
10, 2010.

 Had

mumps, measles, chickenpox during

childhood

Denies

history of pulmonary tuberculosis

hypertension, asthma, thyroid problems, and
cancer.

Denies

previous accident, trauma, and blood

transfusion.

 Patient

denies any heredofamilial diseases, like

Hypertension, Diabetes Mellitus, Bronchial Asthma,
Heart diseases, Lung diseases or Hematologic
disorders.

college graduate, a government employee,

married for 31 years with 2 children, all
apparently well
a non-smoker, non-alcoholic beverage drinker
no food preference
no allergies to food and drugs
currently lives in a well lit and well ventilated
house

Constitutional symptoms: (-) weight loss, (+)weakness

Skin: (-) itchiness, (-) excessive drying and sweating, (-) cyanosis, (-) jaundice

Head: (-) headache

Eyes: (-) photophobia, (-) blurring of vision

Ears: (-) ear pain, (-) deafness, (-) tinnitus, (-) ear discharge

Nose and Sinuses: (-) change in smell, (-) nose bleeding

Neck: (-) pain, (-) limitation of movement, (-) mass

Respiratory: (-) hemoptysis

Cardiovascular: (-) syncope, (+) easy fatigability

Gastrointestinal: (-) dysphagia, (-) diarrhea, (-) constipation, (-)

hematochezia

Genitourinary: (-) urinary frequency, (-) dysuria, (-) incontinence

Nervous system: (-) numbness, (-) loss of memory, (-) confusion, (-) loss of
consciousness

Extremities: (-) joint pains, (-) stiffness, (-) numbness, (-) limitation of
movement

Hematopoietic: (-) bleeding tendency, (-) pallor, (-) easy bruising, (-) history
of transfusion reaction

Endocrine System: (-) intolerance to heat and cold, (-) excessive weight gain
or weight loss

General Survey: conscious, coherent, and

cooperative, looks appropriate for her stated
age, well groomed with clothing appropriate to
weather. Not in cardiorespiratory distress with
the following vital signs:
BP: 110/70 mm Hg
CR: 88 bpm
RR: 19 cpm
Temp: 37.3C
Ht: 5 feet 2 inches
Wt: 52 kg
BMI: 21.13
kg/m2

 Eyes:

thin black eyebrows, fine and evenly

distributed, anicteric sclera, no edema, no
ptosis, negative lid lag test, no tremors,
normally set eyeballs, eyelashes directed
outward without matting, pale palpebral
conjunctiva, anicteric sclera without lesion,
transparent lens and cornea, dark brown iris
with regular contour, pupils normal in size
and reactive to light and accommodation.
Fundoscopic exam reveals (+) ROR, optic disc
not appreciated, (-) hemorrhages, (-)
papilledema

Ear: auricles are symmetrical without tenderness including tragus and

mastoid area, auditory canals are patent, and walls are pink, no discharge
and no lesion. Tympanic membrane is pearly white, intact and with normal
contour, visible cone of light, no bulging, no retractions and no
perforations

Skin: The skin is brown, warm, elastic, mobile, no superficial blood vessels
and no lesions. The hair is fine and evenly distributed. Nails are pink,
smooth and normal nail fold with no lesion. No active dermatoses.

Head: Hair is black and evenly distributed, no scars, clean scalp,

normocephalic, symmetrical cranium, no mass, lesions, and tenderness,
temporal artery is not visible but palpable with strong equal pulsations.

Face: face is oval, symmetrical, with brown skin, no lesions, no masses, no

involuntary muscle movements, normal facie.

Nose and Paranasal Sinuses: nose is symmetrical, no tenderness,

patent vestibule, mucosa is pink, septum is in the midline and
intact, turbinates are not congested, no discharge, no tenderness
over the frontal and maxillary sinuses, positive transillumination
test

Mouth and Pharynx: lips are pinkish, symmetrical, without

lesions; buccal mucosa and gums are pinkish, smooth, without
lesions; floor, roof of the mouth and palate are pinkish. Tongue is
in the midline. Uvula is in the midline, tonsils not enlarged, no
inflammation, pharynx is pink, no lesions, and no exudates.

Neck: Jugular veins are not distended, normal in size, supple, with
well developed muscles with no vein engorgement, no limitation of
movement, no tenderness, trachea in the midline, no palpable
lymph nodes, thyroid gland not palpable.

Thorax and Lungs: skin is brown, no lesions, no dilated superficial

blood vessels, bony thorax is elliptical, symmetrical, without gross
deformities; breathing without effort. Inspiration is longer than
expiration. No tenderness, lung expansion is symmetrical, no
retractions, resonant upon percussion, no lagging, with vesicular
breath sounds. No wheezes, no crackles.

CVS: adynamic precordium, normal rate, regular

rhythm; distinct heart sounds and no murmurs, strong,
equal and regular pulsations, no bruit. Jugular veins are
not distended.

Abdomen: flat, soft, fair skin, inverted umbilicus, no

visible blood vessels, generally tympanitic, normoactive
bowel sounds, no palpable masses, and no tenderness.
Negative for both fluid wave and shifting dullness. Liver
span is 7 cm and spleen was non-palpable.

Extremities: no gross deformities with full and equal

pulses. No edema

NEUROLOGIC EXAMINATION:

Cerebral Funtion: Oriented to time, place, and person.

Cerebellum: can do finger to nose test and alternating pronation and

supination

Cranial Nerves:
I can smell bilaterally
II 2-3 mm pupils, equally reactive to light
III, IV, VI intact EOM
V good masseter tone

VII without facial asymmetry

VIII can hear on both sides

IX and X (+) gag reflex, uvula at the midline

XI can shrug shoulders equally, can elevate shouders against full
resistance, and can move neck from side to side
XII tongue at the midline, no atrophy nor fasciculations

 Motor

5/5 all extremities

Sensory Function:

Function:

100% all extremities

DTRs:

++ all extremities

(-)

Babinski
(-) Nuchal rigidity
(-) Kernig sign
(-) Brudzinskis sign

Salient Features
1 year PTC easy fatigability
dizziness
Self medicated with Multivitamins
and Betahistine which afforded
temporary relief
No consultation done

1 week PTC easy fatigability and

dizziness
Self medicated with
Multivitamins and Betahistine
which afforded temporary relief
No consultation done

2 days PTC easy fatigability

Sought consult at our OPD on Feb
10, 2010

Salient Features
Pertinent PE
- pale palpebral conjunctiva

- no hepatomegaly, no splenomegaly

 Anemia
R/O

electrolyte Imbalance

JI Isidro, Denelyn Marice

XX, 59 years old, female, married, Roman

Catholic, government employee, born on June
6, 1952 in Quezon City, seen for the 1st time at
FEU-NRMF OPD March 10, 2011.

Chief

Complaint: body weakness

1 year PTC, pt. experienced easy fatigability assoc.

w/ dizziness, described as spinning in character

no other s/s noted such as pallor, vomiting, fever,

cough, nor difficulty of breathing

no abnormal vaginal bleeding, melena, hemoptysis,

hematochezia

self-medicated with Multivitamins (Pharmaton) 1

cap OD and Betahistine (Serc) 24 mg/tab 1 tab BID
PRN for dizziness which afforded temporary relief

no consultation done

patient was apparently well until .

week prior to consult, the pt. again

experienced easily fatigability and dizziness,

still

no consultation done, but patient

continued to take her Multivitamins and
Betahistine

 2days

prior to consult, still with easy

fatigabilitythe pt. hence decided to
consult in our OPD Department on March10,
2011.

 Had

mumps, measles, chickenpox during

childhood

Denies

history of pulmonary tuberculosis

hypertension, asthma, thyroid problems, and
cancer.

Denies

previous accident, trauma, and blood

transfusion.

 Patient

denies any heredofamilial diseases, like

Hypertension, Diabetes Mellitus, Bronchial Asthma,
Heart diseases, Lung diseases or Hematologic
disorders.

college graduate, a government employee,

married for 31 years with 2 children, all
apparently well
a non-smoker, non-alcoholic beverage drinker
no food preference
no allergies to food and drugs
currently lives in a well lit and well ventilated
house

Constitutional symptoms: (-) weight loss, (+)weakness

Skin: (-) itchiness, (-) excessive drying and sweating, (-) cyanosis, (-) jaundice

Head: (-) headache

Eyes: (-) photophobia, (-) blurring of vision

Ears: (-) ear pain, (-) deafness, (-) tinnitus, (-) ear discharge

Nose and Sinuses: (-) change in smell, (-) nose bleeding

Neck: (-) pain, (-) limitation of movement, (-) mass

Respiratory: (-) hemoptysis

Cardiovascular: (-) syncope, (+) easy fatigability

Gastrointestinal: (-) dysphagia, (-) diarrhea, (-) constipation, (-)

hematochezia

Genitourinary: (-) urinary frequency, (-) dysuria, (-) incontinence

Nervous system: (-) numbness, (-) loss of memory, (-) confusion, (-) loss of
consciousness

Extremities: (-) joint pains, (-) stiffness, (-) numbness, (-) limitation of
movement

Hematopoietic: (-) bleeding tendency, (-) pallor, (-) easy bruising, (-) history
of transfusion reaction

Endocrine System: (-) intolerance to heat and cold, (-) excessive weight gain
or weight loss

General Survey: conscious, coherent, and

cooperative, looks appropriate for her stated
age, well groomed with clothing appropriate to
weather. Not in cardiorespiratory distress with
the following vital signs:
BP: 110/70 mm Hg
CR: 88 bpm
RR: 19 cpm
Temp: 37.3C
Ht: 5 feet 2 inches
Wt: 52 kg
BMI: 21.13
kg/m2

 Eyes:

thin black eyebrows, fine and evenly

distributed, anicteric sclera, no edema, no
ptosis, negative lid lag test, no tremors,
normally set eyeballs, eyelashes directed
outward without matting, pale palpebral
conjunctiva, anicteric sclera without lesion,
transparent lens and cornea, dark brown iris
with regular contour, pupils normal in size
and reactive to light and accommodation.
Fundoscopic exam reveals (+) ROR, optic disc
not appreciated, (-) hemorrhages, (-)
papilledema

Ear: auricles are symmetrical without tenderness including tragus and

mastoid area, auditory canals are patent, and walls are pink, no discharge
and no lesion. Tympanic membrane is pearly white, intact and with normal
contour, visible cone of light, no bulging, no retractions and no
perforations

Skin: The skin is brown, warm, elastic, mobile, no superficial blood vessels
and no lesions. The hair is fine and evenly distributed. Nails are pink,
smooth and normal nail fold with no lesion. No active dermatoses.

Head: Hair is black and evenly distributed, no scars, clean scalp,

normocephalic, symmetrical cranium, no mass, lesions, and tenderness,
temporal artery is not visible but palpable with strong equal pulsations.

Face: face is oval, symmetrical, with brown skin, no lesions, no masses, no

involuntary muscle movements, normal facie.

Nose and Paranasal Sinuses: nose is symmetrical, no tenderness,

patent vestibule, mucosa is pink, septum is in the midline and
intact, turbinates are not congested, no discharge, no tenderness
over the frontal and maxillary sinuses, positive transillumination
test

Mouth and Pharynx: lips are pinkish, symmetrical, without

lesions; buccal mucosa and gums are pinkish, smooth, without
lesions; floor, roof of the mouth and palate are pinkish. Tongue is
in the midline. Uvula is in the midline, tonsils not enlarged, no
inflammation, pharynx is pink, no lesions, and no exudates.

Neck: Jugular veins are not distended, normal in size, supple, with
well developed muscles with no vein engorgement, no limitation of
movement, no tenderness, trachea in the midline, no palpable
lymph nodes, thyroid gland not palpable.

Thorax and Lungs: skin is brown, no lesions, no dilated superficial

blood vessels, bony thorax is elliptical, symmetrical, without gross
deformities; breathing without effort. Inspiration is longer than
expiration. No tenderness, lung expansion is symmetrical, no
retractions, resonant upon percussion, no lagging, with vesicular
breath sounds. No wheezes, no crackles.

CVS: adynamic precordium, normal rate, regular

rhythm; distinct heart sounds and no murmurs,
strong, equal and regular pulsations, no bruit.
Jugular veins are not distended.

Abdomen: flat, soft, fair skin, inverted umbilicus,

no visible blood vessels, generally tympanitic,
normoactive bowel sounds, no palpable masses,
and no tenderness. Negative for both fluid wave
and shifting dullness. Liver span is 7 cm and spleen
was non-palpable.

Extremities: no gross deformities with full and

equal pulses. No edema

NEUROLOGIC EXAMINATION:

Cerebral Funtion: Oriented to time, place, and person.

Cerebellum: can do finger to nose test and alternating pronation and

supination

Cranial Nerves:
I can smell bilaterally
II 2-3 mm pupils, equally reactive to light
III, IV, VI intact EOM
V good masseter tone

VII without facial asymmetry

VIII can hear on both sides

IX and X (+) gag reflex, uvula at the midline

XI can shrug shoulders equally, can elevate shouders against full
resistance, and can move neck from side to side
XII tongue at the midline, no atrophy nor fasciculations

 Motor

5/5 all extremities

Sensory Function:

Function:

100% all extremities

DTRs:

++ all extremities

(-)

Babinski
(-) Nuchal rigidity
(-) Kernig sign
(-) Brudzinskis sign

Salient Features
1 year PTC easy fatigability,dizziness
Self medicated with Multivitamins
and Betahistine which afforded
temporary relief

No consultation done

1 week PTC easy fatigability and

dizziness
Self medicated with
Multivitamins and Betahistine
which afforded temporary relief
No consultation done

2 days PTC easy fatigability

Sought consult at our OPD on
March 10, 2011

Salient Features
Pertinent PE
- pale palpebral conjunctiva

 Anemia
R/O

electrolyte Imbalance

 Advised

admission (Discharged against

Medical Advice)
For CBC and K

Course at the OPD

S
O

Easy fatigability
110/80 mmHg, 88 bpm, 18 cpm
Pale palpebral conjunctiva

CBC: anemia
(microcytic, hypochromic)
K = normal

PARAMETERS

NORMAL VALUES

3/15/11

RBC COUNT

5.5-6.5 X 1012/L

3.0

HEMOGLOBIN

14-16 g/dL

9.8

HEMATOCRIT

0.42-0.52 L/L

MCV

82-92 fl

MCH

27-33 pg

MCHC

32-38%

PLATELET COUNT

160-380 x 109/L

0.29
60.2
20.8
33
311

WBC COUNT

5-10 x 109/L

6.99

SEGMENTERS

0.55-0.65

LYMPHOCYTES

0.25-0.35

0.62
0.28

MONOCYTES

0.02-0.06

0.09

EOSINOPHILS

0.03-0.05

0.01

T/C IDA

PBS, FOBT, WAUTZ w/ pelvis,

Reticulocyte count
FeSO4 1 tab BID
Referred to HEMA

Considered to be present if the Hgb

concentration or the Hct is below the lower limit
of the 95% reference interval for the individuals
age, sex.

May also be classified by red cell morphology as

macrocytic, normocytic or microcytic

Clinical signs and symptoms result from the

dimiished delivery of O2 to tissues and therefore
are related to the lowered hemoglobin
concentration and blood volume, and dependent
on the rate of this changes

 Modifying

factors are compensatory

adjustments in the:

cardiac output, respiratory rate and oxygen

affinity of hemoglobin.

When anemia develops slowly in a pt. who is

not otherwise severely ill hbg as low as 6
g/dl may develop w/o producing any
discomfort or phys. Signs as long as the pt. is
at rest.

 In

gen. the anemic pt. complains of :

easy fatigability, dyspnea on exertion and often

faintness, vertigo, palpitation and headache.

The

more common physical findings are:

pallor, a bounding pulse, low BP, slight fever,

some dependent edema and systolic murmurs.

Nutritional history r/t drugs or alcohol

intake
family history of anemia

Geographic background and ethnic origin*

Exposure to toxic agents of drugs

s/s r/t other disorders assoc. with anemia

such as:

bleeding, fatigue, malaise, fever, weight loss,

night sweats and other systemic symptoms

Skin- Pallor

-best detected in the skin of mucous membrane of

the mouth,pharynx,conjuctivae,lips,nail beds,and
palms
-pallor alone suggests a nonhemolytic anemia
-pallor plus slight jaundice suggests hemolysis

-pallor plus purpura suggests disorder assssociated

with thrombocytopenia

 Mouth

Smooth tongue suggests the possibility of pernicious

anemia or severe iron deficiency anemia
- Marked hypertrophy of the gums raises the
possibility of acute monocytic leukemia
-

Heart
Forceful heartbeat, strong peripheral pulses and a
systolic flow murmur

Abdomen
-Hepatomegaly and splenomegaly

Lymph Nodes
-Prominent lymphadenopathy suggest the possibility of
hematologic malignancies

Extremities
- Petechiae suggest platelet dysfunction

Clinical Presentation of Anemia

anemia is often recognized w/ abnormal

screening laboratory test

 Complete

Blood Count

RBC count
- Hemoglobin/Hematocrit
- RBC indices
- WBC count
- Platelet Count
Examination of the peripheral blood smear
Reticulocyte count
-

Mean cell volume

(MCV)

Mean cell
hemoglobin (MCH)

Mean corpuscular
Hgb
concentration(MCH
C)

The average volume

of the red blood
cells
-Normal volume=
80-100 fL
-size of rbc

The average
concentration of
hemoglobin per red
cell (chromaticity)
-Normal value= 2634 pg

-The average
concentration of
hemoglobin per red
cell
-NV: 32-36
<32-hypochromic

PARAMETERS

NORMAL VALUES

3/15/11

RBC COUNT

5.5-6.5 X 1012/L

3.0

HEMOGLOBIN

14-16 g/dL

9.8

HEMATOCRIT

0.42-0.52 L/L

MCV

82-92 fl

MCH

27-33 pg

MCHC

32-38%

PLATELET COUNT

160-380 x 109/L

0.29
60.2
20.8
33
311

WBC COUNT

5-10 x 109/L

6.99

SEGMENTERS

0.55-0.65

0.62

LYMPHOCYTES

0.25-0.35

0.28

MONOCYTES

0.02-0.06

0.09

EOSINOPHILS

0.03-0.05

0.01

-Iron deficiency anemia

-Anemia of chronic disorders
-Thalassemias
-Sideroblastic anemias

Serum Ferritin

Serum ferritin LOW

Iron deficiency anemia

Serum ferritin Normal

or
Increased

Anemia of chronic disease

Thalassemia minor

Functional Classification of
Anemia
marrow
production
(hypoproliferative)

defect

red cell maturation defect (ineffective

erythropoiesis)
decreased red
loss/hemolysis)

cell

survival

(blood

On Follow-Up
S

Easy fatigability

Stable VS
Pale palpebral conjunctiva
Elevated reticulocyte
PBS: anisopoikolocytosis, microcytic, hypochromic
red cells, fragmented cells, elliptocyte and
microspherocytosis

T/C IDA

TVS UTZ, B1, B2, SGPT, SGOT, Albumin, LDH,

ALP, PT, PTT, Ferritin, Iron, TIBC
FeSO4 1 tab BID and Multivitamins 1 cap OD

On Follow-Up
S

Easy fatigability

Stable VS
Pale palpebral conjunctiva
Ferritin elevated
Other labs = Normal

T/C Thalassemia

FeSO4 and Multivitamins were discontinued

Advised family screening
Hemoglobin Electrophoresis
Folic Acid 5 mg/tab 1 tab OD

On Follow-Up
S

Easy fatigability

Stable VS
Pale palpebral conjunctiva
Electrophoresis:
Fast moving hgb H (1.7%), Hgb Barts (0.5%),
HgbA2 (1.3%)
low.
Smear showed significant microcytosis.
Asian = compatible w/ hgb H dse

Alpha Thalassemia ( Hemoglobin H

Disease)

EPO injection
Folic Acid 5 mg/tab 1 tab OD

At Present
Folic Acid 5 mg/tab 1 tab OD
EPO 4,000 units subcutaneously

regular CBC monitoring

Hemoglobin Structure
Iron

Heme group
chain

chain

Red Blood Cell

chain

chain
Hellical shape of the
Polypeptide molecule

Hemoglobin is composed of four protein chains,

two and two globin.
Normal adult hemoglobin consists of 2 -globin
protein chains and 2 -globin protein chains
arranged into a heterotetramer.
The globin chains are encoded by two closely
linked genes on chromosome 16.
The globin chains are encoded by a single
gene on chromosome 11.
Thus, in a normal person with two copies of each
chromosome, there are;

Two loci encoding the chain, and

Four loci encoding the chain.

chromosome

Globin chain

Chr. 11 globin gene cluster

epsilon, gamma, delta,

beta

Chr. 16 globin gene cluster

Zeta, alpha

Normal Physiologic Hemoglobins

Globin Chains

Hemoglobin

22

Gower 2

22

Gower 1

22

Portland

2A2

(%)

Stage of
Development

Embryo

60-90

Fetal

2G2

22

95-97

Adult

22

A2

2-3

Adult

NAME

GLOBIN CHAIN

TOTAL (%)

Hgb A

22

95

Hgb A2

22

<3.5

Hgb F

22

<1

1. Hb A - 2 and 2 chains forming a tetramer;

97% adult Hb,

Hb A replaces completely Hb F by 6 months postnatally,

2. Fetal Hb 2 and 2 chains; (1% of adult Hb)

At birth, 70-90% is HbF that falls to 25% by 1st
month and progressively

3. Hb A2 Consists of 2 and 2 chains,

1.5-3.5% in all adult humans

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.

It is the most common single gene

disorder caused by variant or missing
genes that affect the hemoglobin
synthesis.

consists of inherited defects in the rate of

synthesis of one or more of the globin chains
resulting to

imbalanced globin chain production

ineffective erythropoiesis
hemolysis
variable degree of anemia.

It varies, from an asymptomatic to severe, and

varies according to the blood hemoglobin chain
affected.

Thalassemia results in mild to severe anemia, due

to reduced hemoglobin.

Thalassemia
Pathophysiology

In people with thalassemia, the genes, that code for

hemoglobin synthesis, are missing or variant
(different than the normal genes).

Thalassemia patients produce a deficiency of either

or globin. The thalassemias are classified
according to which chain of the hemoglobin
molecule is affected.

Thalassemia
Pathophysiology

Anemia result from lack of adequate Hb A tissue

hypoxia Erythropoietin (EPO) production
erythropoiesis in the marrow and sometimes
extramedullary expansion of medullary cavity of
various bones
Liver spleen enlarge extramedullay
hematopoiesis
In thalassemias, production of the globin chain
is affected, while,
In thalassemia production of the globin chain is
affected.

Consequences of decreased -chain production in

Thalassemia
Reduced concentrations of all normal hemoglobins (A, A2, F)
Assembly of excess - class chains into abnormal hemoglobin
tertramers: (Hgb H- 4) (Hgb Bart-4)

Properties of abnormal hemoglobins in Thalassemia

Hgb

property

Hbg H (4)

unstable

Hgb Bart (4)

Very high oxygen affinity

Named for the affected blood hemoglobin chains

are affected two protein chains that make up
normal hemoglobin.

The genes for each type of thalassemia are passed

from parents to their children.

Thalassemia - Classification

Two main types:

Alpha () thalassemia: Synthesis of chain is

suppressed level of all 3 normal Hb A (2 , 2), Hb A2
(2 ,2), HbF (2 , 2 ) reduced,
Silent carrierone gene affected
Thalassemia traittwo genes affected
Hemoglobin H disease Hb H (4)three genes
affected
Alpha hydrops fetalis Hb-Barts (4)four genes
affected;

Pathophysiology
Gene deletions on chromosome 16
Genes, called HBA1 and HBA2, hold instructions
for making the - globin chain of Hemoglobin,
The Alpha () thalassemias involve these genes,
inherited in a Mendelian recessive fashion,
There are two gene loci and so four alleles. It is
connected to the deletion of alpha globin locus on
16p chromosome,
Defective synthesis of -globin chain results in;
Excess of - chains - in the fetus (Hb-Barts ( 4)
/ Hydrops Fetalis)
Excess of -chains - in the adults (Hemoglobin H
Disease (Hb H (4).

Alpha () thalassemia

Four genes are involved in making the - globin part

of hemoglobintwo from each parent.
Alpha () thalassemia occurs when one or more of
these genes is variant or missing;

Alpha () Thalassemia - Classification

NO. OF GENES
AFFECTED

GENOTYPE

CLINICAL CLASSIFICATION

1 Gene

/ -

Silent Carrier

2 Genes

- / - or
/ - -

- thalassemia trait

3 Genes

-/--

Hb H Disease

4 Genes

--/--

Hb Barts / Hydrops fetalis

*Patients may or may not be transfusion dependent.

Alpha () thalassemia minima / Silent Carriers: People with only

one gene affected and have no sign of illness,(diagnosed only by DNA
analysis)
Alpha () thalassemia trait / Alpha () thalassemia minor: People
with two genes affected, have mild anemia (hypochromia & microcytosis
with Target cells, MCV<80fL)) and are considered carriers,

Hemoglobin H Disease (Hb H (4):

People with three genes affected have moderate anemia

(Hb 8-9 gm/dl), (microcytosis with Target cells).
HbH cant release O2 to tissues, because affinity is greater
than HbA.
May/not be transfusion dependent,

Hydrops Fetalis (Hb Barts) / Alpha ()

thalassemia major (4): Babies with all four genes
affected,
Most severe manifestation of alpha thalassemia,
Hb Barts has 4
Stillborn or die within a few hours after birth

 Hemoglobin H Disease (clin.

Manifestations)
- lifelong anemia(moderate to marked)
w/ variable splenomegaly
Expansion in erythropoiesis
changes are unusual)

(bone

Hb Barts (Hydrops Fetalis)

Hydrops Fetalis (Hb Barts) / Alpha () thalassemia

major (4): Babies with all four genes affected,
Most severe manifestation of alpha thalassemia,

Severe hypoxia, as Hb Barts has high affinity for O2,

Clinically: Severe anemia , edematous, mild jaundice, ascites,
hepatosplenomegaly, cardiac failure
Mostly fatal unless intrauterine blood transfusions,
Usually stillborn or die shortly after birth.

Hydrops Fetalis

Hydrops fetalis usually stems from fetal anemia of either an immune

or non-immune cause. when the heart needs to pump a much greater
volume of blood to deliver the same amount of oxygen.

Hb Barts (Hydrops Fetalis)

DIAGNOSIS:

Hb electrophoresis:
80-90 % Hb Barts
Hb H
Hb Portland
No Hb A, Hb A2 or Hb F
TREATMENT:
Immediate exchange transfusion.

Alpha () thalassemia

DIAGNOSIS :
Complete

Blood Count, Peripheral Smear, Bone

Marrow study,

Hgb

Hb

H brilliant cresyl blue

electrophoresis for HbH and Hb Barts;

HbH -Rapidly moving band that migrates well ahead of Hgb

A

Alpha () thalassemia

TREATMENT:

Blood transfusion , iron chelation therapy For

transfusion dependent cases,
Avoidance of oxidant drugs,
Prompt treatment of infections,
Folic acid supplementation,
Splenectomy,
Bone Marrow transplantation,
Gene therapy.

Often patient is asymptomatic and is unprepared for

the acute complications that occur during :

infection, pregnancy, and drug exposure

include hemolytic and aplastic anemic episodes

Folic acid supplements & avoidance of oxidative
compounds & medications are recommended

In mild cases

biannual visits are adequate

In more severe cases

more frequent visits indicated

 At

routine visits

growth, development, facial bone deformity,

dental status, and hepatosplenomegaly -should
be monitored
Routine monitoring of hgb levels -required

 Patients

with hemoglobin H disorders usually

develop neonatal anemia

Splenomegaly & hypersplenism relatively common.

Splenectomy usually ameliorates the severe anemia noted in

nondeletional hemoglobin H cases

monitoring of iron stores with quantitative imaging of

the liver is indicated*.

Cardiac function monitoring is indicated

frequency determined by the anemia and the iron-overload status

Gallstones

nontransfused patients-imaging should be initiated in early adolescence

frequently occur in hemoglobin H disease, and cholecystectomy is

indicated in

symptomatic patients

Bone-density measurement

should be initiated in earlyadolescence

Pregnancy

requires more frequent monitoring because of the risk of

severe anemia and pre-eclampsia.

 Prevention
- prospective gene counseling
- prenatal diagnosis

Thalassemia - Classification

Beta () thalassemia: Synthesis of chain is

suppressed adult Hb is suppressed,
Thalassemia minorone abnormal gene,
Heterozygous, usually asymptomatic,
Thalassemia intermedia / + Thalassemia
Reduced synthesis of globin chain, wide
variety of genotypes; Homozygous as well as
heterozygous,
Thalassemia major / 0 Thalassemia
(Cooley's anemia)two abnormal genes. Absent
synthesis of globin chain, homozygous, Hb A
absent.

Feature

Thalassemia Trait

Thalassemia Intermedia

Thalassemia Major

Genetic pathology

One -globin gene carrying

a thalassemia mutation

Two -globin genes

carrying a thalassemia
mutation, at least one of
which is mild; one -globin
thalassemia mutation in
combination with excess globin genes (less common)

Two -globin carrying a

severe thalassemia
mutation

Clinical manifestation

Mild or no anemia, with

variable microcytosis
(mcv,60 to normal);

Mild to moderate anemia;

relative independence from
transfusion;

Severe anemia requiring

regular transfusions
beginning in infancy;

no splenomegaly; no bone
disease

prominent splenomegaly
and bone deformities;
variable degrees of iron
overload depending on
severity of anemia and
transfusion requirement

splenomegaly and bone

disease depending on the
efficacy of transfusion
therapy; severe iron
overload

Severity

Asymptomatic

From asymptomatic to
severely symptomatic

Lifelong supportive care

required

Ameliorating genetic
factors

Presence of concurrent thalassemia

Presence of concurrent thalassemia; elevated

hemoglobin F

Presence of concurrent thalassemia; elevated

hemoglobin F

Free chains(very
unstable and denature
rapidly)
Form precipitates within
the rbc

Destroyed in marrow
before release in
bloodstream

Ineffective erythropoiesis

Released cells from

marrow

Destroyed prematurely
in spleen

 Phenomenal

increase in erythropoiesis

vast expansion of marrow red cell prodn

Persistence

of erythropoiesis in spleen and liver

(extramedullary hematopoiesis)

Massive

marrow expansion deranges growth &

development
Chipmunk facies
maxillary
hyperplasia
frontal bossing

Cortical invasion by
erythroid
elmentspathologic
fracture of long
bones

 Constription

in
caloric resources
to support
erytrhopoiesis

Endo dysfunction
Susceptibility to
infection
death

Hemolytic

anemia

Leg ulcers
Gallstones
High output CHF
Hepatosplenomegaly

chain of events following globin chain imbalance and

the accumulation of excess a-chains
ineffective erythropoiesis leading to anemia,
bone marrow expansion, skeletal deformities
increased GI iron absorption

CHIPMUNK FACIES

Detection and Characterization of

Hemoglobinopathies
electrophoretic techniques are used for
routine clinical purposes
electrophoresis at pH 8.6 on cellulose
acetate membranes (simple, inexpensive,
reliable as initial screening)

 Complete characterization, including amino acid

sequencing or gene cloning and sequencingavailable in several labs around the world

PCR, allele-specific oligonucleotide

hybridization, and automated DNA sequencing
for identification of globin gene mutations

 laboratory evaluation remains an

adjunct, rather than primary diagnostic
aid
diagnosis is best established by
recognition of characteristic history,
physical findings, PBS morphology and
abnormalities of CBC

Alpha () thalassemia

TREATMENT:

Blood transfusion , iron chelation therapy For

transfusion dependent cases,
Avoidance of oxidant drugs,
Prompt treatment of infections,
Folic acid supplementation,
Splenectomy,
Bone Marrow transplantation,
Gene therapy.

 Transfusion

 - 8-12-hour overnight pump-driven

infusion in subcutaneous tissues of
anterior abdominal wall
Most effective route of administration

 Iron Chelation
local
erythema
subcutaneous nodules

and

painful

- rare severe allergic reaction (5-10

mg hydrocortisone)

 Iron Chelation

- oral: Deferiprone and Deferasirox

- Deferiprone 75 mg/kg in 3 daily doses
(neutropenia, agranulocytosis)

 Iron Chelation

- Deferasirox 5 or 10 mg/kg per day or

higher
- GIT, rashes, increase creatinine

 Stem Cell Transplantation

- infection and GVHD