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XX, 59 years old, female, married, RomanCatholic, 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
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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
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2days prior to consult, still with easy
fatigabilitythe pt. hence decided to
consult in our OPD Department on February
10, 2010.
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Had mumps, measles, chickenpox duringchildhood
Denies history of pulmonary tuberculosishypertension, asthma, thyroid problems, andcancer.
Denies previous accident, trauma, and bloodtransfusion.
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Patient denies any heredofamilial diseases, like
Hypertension, Diabetes Mellitus, Bronchial Asthma,
Heart diseases, Lung diseases or Hematologic
disorders.
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a college graduate, a government employee,
married for 31 years with 2 children, allapparently 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
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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 ofmovement
Hematopoietic: (-) bleeding tendency, (-) pallor, (-) easy bruising, (-) historyof transfusion reaction
Endocrine System: (-) intolerance to heat and cold, (-) excessive weight gainor weight loss
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General Survey: conscious, coherent, andcooperative, 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
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Eyes: thin black eyebrows, fine and evenly
distributed, anicteric sclera, no edema, noptosis, 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 discnot appreciated, (-) hemorrhages, (-)
papilledema
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Ear: auricles are symmetrical without tenderness including tragus and
mastoid area, auditory canals are patent, and walls are pink, no dischargeand 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 vesselsand 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, noinvoluntary muscle movements, normal facie.
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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, withoutlesions; 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, withwell 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 superficialblood 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 vesicularbreath sounds. No wheezes, no crackles.
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CVS: adynamic precordium, normal rate, regularrhythm; 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, novisible blood vessels, generally tympanitic, normoactive
bowel sounds, no palpable masses, and no tenderness.
Negative for both fluid wave and shifting dullness. Liverspan is 7 cm and spleen was non-palpable.
Extremities: no gross deformities with full and equal
pulses. No edema
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NEUROLOGIC EXAMINATION:
Cerebral Funtion: Oriented to time, place, and person.
Cerebellum: can do finger to nose test and alternating pronation andsupination
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 midlineXI – can shrug shoulders equally, can elevate shouders against fullresistance, and can move neck from side to side
XII – tongue at the midline, no atrophy nor fasciculations
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Motor Function:
5/5 all extremities
Sensory Function: 100% all extremities
DTR’s:
++ all extremities
(-) Babinski
(-) Nuchal rigidity
(-) Kernig sign (-) Brudzinski’s sign
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Salient Features
1 year PTC → easy fatigability
• dizzinessSelf medicated with Multivitamins
and Betahistine which afforded
temporary relief No consultation done
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1 week PTC → easy fatigability and
dizziness
Self medicated with
Multivitamins and Betahistine
which afforded temporary relief
No consultation done
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2 days PTC → easy fatigability
Sought consult at our OPD on Feb
10, 2010
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Salient Features
Pertinent PE
– - pale palpebral conjunctiva
– - no hepatomegaly, no splenomegaly
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Anemia
R/O electrolyte Imbalance
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JI Isidro, Denelyn Marice
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XX, 59 years old, female, married, RomanCatholic, 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
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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) 1cap OD and Betahistine (Serc) 24 mg/tab 1 tab BID
PRN for dizziness which afforded temporary relief
no consultation done
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patient was apparently well until ….
1 week prior to consult, the pt. againexperienced easily fatigability and dizziness,
still no consultation done, but patient
continued to take her Multivitamins and
Betahistine
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2days prior to consult, still with easy
fatigabilitythe pt. hence decided to
consult in our OPD Department on March10,
2011.
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Had mumps, measles, chickenpox duringchildhood
Denies history of pulmonary tuberculosishypertension, asthma, thyroid problems, and
cancer.
Denies previous accident, trauma, and bloodtransfusion.
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Patient denies any heredofamilial diseases, likeHypertension, Diabetes Mellitus, Bronchial Asthma,
Heart diseases, Lung diseases or Hematologic
disorders.
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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, (-) historyof transfusion reaction
Endocrine System: (-) intolerance to heat and cold, (-) excessive weight gainor weight loss
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General Survey: conscious, coherent, andcooperative, 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
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Eyes: thin black eyebrows, fine and evenly
distributed, anicteric sclera, no edema, noptosis, 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 discnot appreciated, (-) hemorrhages, (-)
papilledema
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Ear: auricles are symmetrical without tenderness including tragus and
mastoid area, auditory canals are patent, and walls are pink, no dischargeand 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 vesselsand 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, noinvoluntary muscle movements, normal facie.
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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, withwell 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 superficialblood 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 vesicularbreath sounds. No wheezes, no crackles.
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CVS: adynamic precordium, normal rate, regularrhythm; 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 andequal pulses. No edema
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NEUROLOGIC EXAMINATION:
Cerebral Funtion: Oriented to time, place, and person.
Cerebellum: can do finger to nose test and alternating pronation andsupination
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 midlineXI – can shrug shoulders equally, can elevate shouders against fullresistance, and can move neck from side to side
XII – tongue at the midline, no atrophy nor fasciculations
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Motor Function:
5/5 all extremities
Sensory Function: 100% all extremities
DTR’s:
++ all extremities
(-) Babinski
(-) Nuchal rigidity
(-) Kernig sign (-) Brudzinski’s sign
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Salient Features
1 year PTC → easy fatigability,dizziness
Self medicated with Multivitaminsand Betahistine which afforded
temporary relief
No consultation done
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1 week PTC → easy fatigability and
dizziness
Self medicated with
Multivitamins and Betahistine
which afforded temporary relief
No consultation done
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2 days PTC → easy fatigability
Sought consult at our OPD on
March 10, 2011
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Salient Features
Pertinent PE
– - pale palpebral conjunctiva
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Anemia
R/O electrolyte Imbalance
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Advised admission (Discharged against
Medical Advice)
For CBC and K
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Course at the OPD
»
S Easy fatigability
O 110/80 mmHg, 88 bpm, 18 cpmPale palpebral conjunctiva
CBC: anemia (microcytic, hypochromic)K = normal
PARAMETERS NORMAL VALUES 3/15/11
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PARAMETERS NORMAL VALUES 3/15/11
RBC COUNT 5.5-6.5 X 1012/L 3.0
HEMOGLOBIN 14-16 g/dL
9.8HEMATOCRIT 0.42-0.52 L/L 0.29
MCV 82-92 fl 60.2
MCH 27-33 pg 20.8
MCHC 32-38% 33
PLATELET COUNT 160-380 x 109/L 311
WBC COUNT 5-10 x 109/L 6.99
SEGMENTERS 0.55-0.65 0.62LYMPHOCYTES 0.25-0.35 0.28
MONOCYTES 0.02-0.06 0.09
EOSINOPHILS 0.03-0.05 0.01
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A T/C IDA
P PBS, FOBT, WAUTZ w/ pelvis,Reticulocyte count
FeSO4 1 tab BIDReferred to HEMA
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Considered to be present if the Hgbconcentration or the Hct is below the lower limitof the 95% reference interval for the individual’sage, sex.
May also be classified by red cell morphology asmacrocytic, normocytic or microcytic
Clinical signs and symptoms result from thedimiished delivery of O2 to tissues and thereforeare related to the lowered hemoglobinconcentration and blood volume, and dependenton the rate of this changes
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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 anydiscomfort or phys. Signs as long as the pt. is
at rest.
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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.
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• Nutritional history r/t drugs or alcoholintake
• family history of anemia
• Geographic background and ethnic origin*
• Exposure to toxic agents of drugs
• s/s r/t other disorders assoc. with anemiasuch as:• bleeding, fatigue, malaise, fever, weight loss,
night sweats and other systemic symptoms
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Skin- Pallor
-best detected in the skin of mucous membrane ofthe mouth,pharynx,conjuctivae,lips,nail beds,andpalms
-pallor alone suggests a nonhemolytic anemia
-pallor plus slight jaundice suggests hemolysis
-pallor plus purpura suggests disorder assssociatedwith thrombocytopenia
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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
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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
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Clinical Presentation of Anemia anemia is often recognized w/ abnormal
screening laboratory test
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Complete Blood Count
- RBC count
- Hemoglobin/Hematocrit
- RBC indices- WBC count
- Platelet Count
Examination of the peripheral blood smear
Reticulocyte count
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- Mean cell volume(MCV)
Mean cellhemoglobin (MCH)
Mean corpuscularHgbconcentration(MCHC)
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= 26-
34 pg
-The average
concentration of
hemoglobin per red
cell
-NV: 32-36
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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 0.29
MCV 82-92 fl 60.2
MCH 27-33 pg 20.8
MCHC 32-38% 33PLATELET COUNT 160-380 x 109/L 311
WBC COUNT 5-10 x 109/L 6.99
SEGMENTERS 0.55-0.65 0.62LYMPHOCYTES 0.25-0.35 0.28
MONOCYTES 0.02-0.06 0.09
EOSINOPHILS 0.03-0.05 0.01
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-Iron deficiency anemia
-Anemia of chronic disorders
-Thalassemias-Sideroblastic anemias
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Serum Ferritin
Serum ferritin LOW
Serum ferritin Normal
or
Increased
Iron deficiency anemia Anemia of chronic disease
Thalassemia minor
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i l l ifi i f
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Functional Classification ofAnemia
marrow production defect
(hypoproliferative)
red cell maturation defect (ineffective
erythropoiesis)
decreased red cell survival (blood
loss/hemolysis)
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On Follow-Up
»
S Easy fatigability
O Stable VSPale palpebral conjunctivaElevated reticulocytePBS: anisopoikolocytosis, microcytic, hypochromicred cells, fragmented cells, elliptocyte andmicrospherocytosis
A T/C IDA
P TVS UTZ, B1, B2, SGPT, SGOT, Albumin, LDH,ALP, PT, PTT, Ferritin, Iron, TIBC
FeSO4 1 tab BID and Multivitamins 1 cap OD
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On Follow-Up
»
S Easy fatigability
O Stable VSPale palpebral conjunctivaFerritin elevatedOther labs = Normal
A T/C Thalassemia
P FeSO4 and Multivitamins were discontinuedAdvised family screeningHemoglobin ElectrophoresisFolic Acid 5 mg/tab 1 tab OD
On Follow-Up
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On Follow Up
»
S Easy fatigability
O Stable VSPale palpebral conjunctivaElectrophoresis:Fast moving hgb H (1.7%), Hgb Bart’s (0.5%),HgbA2 (1.3%) low.Smear showed significant microcytosis.Asian = compatible w/ hgb H dse
A Alpha Thalassemia ( Hemoglobin HDisease)
P EPO injectionFolic Acid 5 mg/tab 1 tab OD
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At Present
Folic Acid 5 mg/tab 1 tab OD
EPO 4,000 units subcutaneously
regular CBC monitoring
H l bi St t
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Hemoglobin Structure
β chain
α chain β chain
Heme group
α chain
Iron
Red Blood Cell
Hellical shape of thePolypeptide molecule
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Hemoglobin is composed of four protein chains,
two α and two β globin. Normal adult hemoglobin consists of 2 β-globin
protein chains and 2 α-globin protein chainsarranged into a heterotetramer.
The α globin chains are encoded by two closelylinked genes on chromosome 16.
The β globin chains are encoded by a singlegene on chromosome 11.
Thus, in a normal person with two copies of each
chromosome, there are; Two loci encoding the β chain, and
Four loci encoding the α chain.
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chromosome Globin chain
Chr. 11 Β globin gene cluster epsilon, gamma, delta,
beta
Chr. 16 α globin gene cluster Zeta, alpha
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Normal Physiologic Hemoglobins
Globin Chains Hemoglobin (%) Stage of
Development
α2ε2Gower 2
Embryoζ2ε2Gower 1
ζ2γ2 Portland
α2Aγ2
F
60-90 Fetal
α2Gγ2
α2β2 A 95-97 Adult
α2δ2A2 2-3 Adult
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NAME GLOBIN CHAIN TOTAL (%)
Hgb A α2β2 95
Hgb A2 α2δ2
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1. Hb A - 2 α and 2 β chains forming a tetramer; 97% adult Hb,
Hb A replaces completely Hb F by 6 months postnatally,
2. Fetal Hb – 2α and 2γ 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 α and 2 δ chains, 1.5-3.5% in all adult humans
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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 genedisorder caused by variant or missing
genes that affect the hemoglobin
synthesis.
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consists of inherited defects in the rate ofsynthesis of one or more of the globin chainsresulting 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 chainaffected.
Thalassemia results in mild to severe anemia, due
to reduced hemoglobin.
Thalassemia
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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
α or β globin. The thalassemias are classified
according to which chain of the hemoglobin
molecule is affected.
Thalassemia
Pathophysiology
Thalassemia
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Anemia result from lack of adequate Hb A tissuehypoxia ↑ Erythropoietin (EPO) production ↑erythropoiesis in the marrow and sometimesextramedullary expansion of medullary cavity of
various bones Liver spleen enlarge extramedullay
hematopoiesis
In α thalassemias, production of the α globin chainis affected, while,
In β thalassemia production of the β globin chain isaffected.
Thalassemia
Pathophysiology
Consequences of decreased α-chain production in
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q p
α Thalassemia
•Reduced concentrations of all normal hemoglobins (A, A2, F)•Assembly of excess β- class chains into abnormal hemoglobin
tertramers: (Hgb H- β4) (Hgb Bart-γ4)
Properties of abnormal hemoglobins in α Thalassemia
Hgb property
Hbg H (β4) unstable
Hgb Bart (γ4) Very high oxygen affinity
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Named for the affected blood hemoglobin chains
are affected two protein chains that make upnormal hemoglobin.
The genes for each type of thalassemia are passed
from parents to their children.
Thalassemia - Classification
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Two main types:
Alpha ( ) thalassemia: Synthesis of α chain issuppressed level of all 3 normal Hb A (α2 , β2), Hb A2(α2 ,δ2), HbF (α2 , 2 ) reduced,
Silent carrier—one gene affected
Thalassemia trait—two genes affected
Hemoglobin H disease Hb H (β4)—three genes
affected
Alpha hydrops fetalis Hb-Bart’s ( 4)—four genes
affected;
Thalassemia Classification
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Gene deletions on chromosome 16 Genes, called HBA1 and HBA2, hold instructions
for making the - globin chain of Hemoglobin,
The Alpha (α) 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 α-globin chain results in;Excess of - chains - in the fetus (Hb-Bart’s (γ 4)
/ Hydrops Fetalis)
Excess of β-chains - in the adults (Hemoglobin H
Disease (Hb H ( β4).
Pathophysiology
Alpha ( ) thalassemia
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Four genes are involved in making the - globin partof hemoglobin—two from each parent.
Alpha ( ) thalassemia occurs when one or more ofthese genes is variant or missing;
Alpha ( ) thalassemia
Alpha ( ) Thalassemia - Classification
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Alpha ( ) Thalassemia Classification
NO. OF GENESAFFECTED
GENOTYPE CLINICAL CLASSIFICATION
1 Gene αα / - α Silent Carrier
2 Genes - α / - α or αα / - -
α - thalassemia trait
3 Genes - α / - - Hb H Disease
4 Genes - - / - - Hb Barts / Hydrops fetalis
*Patients may or may not be transfusion dependent.
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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
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Hemoglobin H Disease (clin.Manifestations)
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Manifestations)
– - lifelong anemia(moderate to marked)w/ variable splenomegaly
– Expansion in erythropoiesis (bonechanges are unusual)
Hb Barts (Hydrops Fetalis)
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Hydrops Fetalis (Hb Barts) / Alpha ( ) thalassemiamajor (γ4): 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.
Hb Barts (Hydrops Fetalis)
Hydrops Fetalis
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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)
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DIAGNOSIS:
Hb electrophoresis:
80-90 % Hb Bart’s
Hb H
Hb Portland No Hb A, Hb A2 or Hb F
TREATMENT:
Immediate exchange transfusion.
Hb Barts (Hydrops Fetalis)
Alpha ( ) thalassemia
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DIAGNOSIS :
Complete Blood Count, Peripheral Smear, BoneMarrow study,
Hgb H – brilliant cresyl blue
Hb electrophoresis – for HbH and Hb Barts; HbH -Rapidly moving band that migrates well ahead of Hgb
A
p ( )
Alpha ( ) thalassemia
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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.
p ( )
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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
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At routine visits… growth, development, facial bone deformity,
dental status, and hepatosplenomegaly -should
be monitored
Routine monitoring of hgb levels -required
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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
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monitoring of iron stores with quantitative imaging of
the liver is indicated*. nontransfused patients-imaging should be initiated in early adolescence
Cardiac function monitoring is indicated frequency determined by the anemia and the iron-overload status
Gallstones frequently occur in hemoglobin H disease, and cholecystectomy is
indicated in
symptomatic patients
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Bone-density measurement should be initiated in earlyadolescence
Pregnancy requires more frequent monitoring because of the risk of
severe anemia and pre-eclampsia.
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Prevention
• - prospective gene counseling
•
- prenatal diagnosis
Thalassemia - Classification
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Beta ( ) thalassemia: Synthesis of β chain is
suppressed adult Hb is suppressed, β Thalassemia minor —one abnormal gene,
Heterozygous, usually asymptomatic,
β Thalassemia intermedia / β+ Thalassemia—
Reduced synthesis of β globin chain, widevariety of genotypes; Homozygous as well as
heterozygous,
β Thalassemia major / β 0 Thalassemia
(Cooley's anemia)—two abnormal genes. Absentsynthesis of β globin chain, homozygous, Hb A –
absent.
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Feature Thalassemia Trait Thalassemia Intermedia Thalassemia Major
Genetic pathology One β-globin gene carrying
a thalassemia mutation
Two β-globin genes
carrying a thalassemiamutation, at least one of
which is mild; one β-globin
thalassemia mutation in
combination with excess α-
globin genes (less common)
Two β-globin carrying a
severe thalassemiamutation
Clinical manifestation Mild or no anemia, with
variable microcytosis
(mcv,60 to normal);
no splenomegaly; no bone
disease
Mild to moderate anemia;
relative independence from
transfusion;
prominent splenomegaly
and bone deformities;
variable degrees of ironoverload depending on
severity of anemia and
transfusion requirement
Severe anemia requiring
regular transfusions
beginning in infancy;
splenomegalyand bone
disease depending on the
efficacy of transfusiontherapy; severe iron
overload
Severity Asymptomatic From asymptomatic toseverely symptomatic
Lifelong supportive carerequired
Ameliorating genetic
factors
Presence of concurrent α-
thalassemia
Presence of concurrent α-
thalassemia; elevatedhemoglobin F
Presence of concurrent α-
thalassemia; elevatedhemoglobin F
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Free α chains(veryunstable and denaturerapidly)
Form precipitates withinthe rbc
Destroyed in marrowbefore release inbloodstream
Ineffective erythropoiesis
Released cells frommarrow
Destroyed prematurelyin spleen
Phenomenal increase in erythropoiesis
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vast expansion of marrow red cell prod’n
Persistence of erythropoiesis in spleen and liver
(extramedullary hematopoiesis)
Massive marrow expansion deranges growth &development
“Chipmunk facies”
maxillaryhyperplasia
frontal bossing
Cortical invasion by
erythroidelmentspathologic
fracture of long
bones
Constription in
l iHemolytic anemia
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caloric resources
to support
erytrhopoiesis
Endo dysfunction
Susceptibility to
infection
death
Hemolytic anemia
Leg ulcersGallstones
High output CHF
Hepatosplenomegaly
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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
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CHIPMUNK FACIES
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Detection and Characterization of
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Detection and Characterization ofHemoglobinopathies
electrophoretic techniques are used for
routine clinical purposes
electrophoresis at pH 8.6 on cellulose
acetate membranes (simple, inexpensive,
reliable as initial screening)
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Complete characterization, including amino acid
sequencing or gene cloning and sequencing-
available in several labs around the world
PCR, allele-specific oligonucleotide
hybridization, and automated DNA sequencing
for identification of globin gene mutations
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laboratory evaluation remains an
adjunct, rather than primary diagnostic
aid
diagnosis is best established by
recognition of characteristic history,
physical findings, PBS morphology andabnormalities of CBC
Alpha ( ) thalassemia
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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
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– - 8-12-hour overnight pump-driveninfusion in subcutaneous tissues of
anterior abdominal wall
–
Most effective route of administration
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Iron Chelation
– - local erythema and painful
subcutaneous nodules
– - rare severe allergic reaction (5-10
mg hydrocortisone)
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Iron Chelation
– - oral: Deferiprone and Deferasirox
– - Deferiprone 75 mg/kg in 3 daily doses(neutropenia, agranulocytosis)
Iron Chelation
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– - Deferasirox 5 or 10 mg/kg per day or
higher
– - GIT, rashes, increase creatinine
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Stem Cell Transplantation
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– - infection and GVHD
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