thalassemia report edited2

8/9/2019 Thalassemia Report Edited2

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2/121

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


3/121

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


4/121


5/121

2days prior to consult, still with easy

fatigabilitythe pt. hence decided to

consult in our OPD Department on February

10, 2010.


6/121

Had mumps, measles, chickenpox duringchildhood

Denies history of pulmonary tuberculosishypertension, asthma, thyroid problems, andcancer.

Denies previous accident, trauma, and bloodtransfusion.


7/121

Patient denies any heredofamilial diseases, like

Hypertension, Diabetes Mellitus, Bronchial Asthma,

Heart diseases, Lung diseases or Hematologic

disorders.


8/121

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


9/121

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


10/121

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


11/121

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


12/121

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


15/121

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


17/121

Salient Features

1 year PTC → easy fatigability

• dizzinessSelf medicated with Multivitamins

and Betahistine which afforded

temporary relief No consultation done


18/121

1 week PTC → easy fatigability and

dizziness

Self medicated with

Multivitamins and Betahistine

which afforded temporary relief

No consultation done


19/121

2 days PTC → easy fatigability

Sought consult at our OPD on Feb

10, 2010


20/121

Salient Features

Pertinent PE

– - pale palpebral conjunctiva

– - no hepatomegaly, no splenomegaly


21/121

Anemia

R/O electrolyte Imbalance


22/121

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


24/121

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


25/121

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


26/121

2days prior to consult, still with easy

fatigabilitythe pt. hence decided to

consult in our OPD Department on March10,

2011.


27/121

Had mumps, measles, chickenpox duringchildhood

Denies history of pulmonary tuberculosishypertension, asthma, thyroid problems, and

cancer.

Denies previous accident, trauma, and bloodtransfusion.


28/121

Patient denies any heredofamilial diseases, likeHypertension, Diabetes Mellitus, Bronchial Asthma,

Heart diseases, Lung diseases or Hematologic

disorders.


29/121


30/121

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


31/121

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


32/121

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


33/121

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.


34/121

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.


35/121

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


36/121

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


37/121

Motor Function:

5/5 all extremities

Sensory Function: 100% all extremities

DTR’s:

++ all extremities

(-) Babinski

(-) Nuchal rigidity

(-) Kernig sign (-) Brudzinski’s sign


38/121

Salient Features

1 year PTC → easy fatigability,dizziness

Self medicated with Multivitaminsand Betahistine which afforded

temporary relief



39/121

1 week PTC → easy fatigability and

dizziness

Self medicated with

Multivitamins and Betahistine

which afforded temporary relief



40/121

2 days PTC → easy fatigability

Sought consult at our OPD on

March 10, 2011


41/121

Salient Features

Pertinent PE

– - pale palpebral conjunctiva


42/121

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


66/121

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 - 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


86/121

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.


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.



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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.




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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 ( )



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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


thalassemia; elevatedhemoglobin F


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



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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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thalassemia report edited2

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