Megaloblastic Anemia

= Anemias Of Abnormal Nuclear Development

etiology
Vitamin B12 deficiency/Pernicious anemia
Folate deficiency
Combined deficiencies
Deficiency of B12
A. Inadequate intake
1. Dietary
2. Maternal deficiency
B. Defective absorption
1. Lack of intrinsic factor
a. Congenital deficiency of intrinsic factor
b. u!enile "ernicious anemia
c. u!enile "ernicious anemia #it$ multi"le endocrino"at$ies
d. Pernicious anemia
e. %astrectomy
2. Failure of intestinal absor"tion
a. &"esific !itamin B12 malabsor"tion ' (merslund)%rasbeck
syndrome
b. %enerali*ed malabsor"tion ' intestinal resection+ regional
ileitis+ celiac disease
c. Com"etition for !itamin B12 syndrome of bacterial o!ergro#t$
in t$e small bo#el+ fis$ ta"e#orm infestation
C. Defective transport
1. Congenital deficiency of ,C ((+ mutation in ,C ((
D. Disorders of metabolism
1. Congenital
2. -c.uired+ es"ecially drug induced
Folic -cid Deficiency
A. Inadequate intake/increased requirements
1. Malnouris$ment
2. /0cessi!e cooking
1. &"ecial diets
2. Pregnancy/lactation
3. 4e#born "eriod/early c$ild$ood
5. C$ronic $emolytic anemia+ malignancy
6. /0foliati!e skin disease
B. Defective absorption
1. Congenital
2. -c.uired
C. Disorders of metabolism/uptake
1. Congenital
2. -c.uired
D. Drugs
etiology : Pernicious Anemia
%astric atro"$y
7esults in decreased secretion of intrinsic factor
8(F9 by "arietal cells
Destruction of !itamin B12 in %( tract
:t$er causes
etiology : Folate Defciency

Dietary deficiency
(nfant
malnutrition
KKA-481 Mira Yulianti (01-107)

-lco$olic cirr$osis

Pregnancy
Folate
antagonists
Patophisiology
B12 and folate deficiencies result in defecti!e
D4- synt$esis
,$is results in an abnormal cell maturation
"rocess
Most likely megaloblastic cells die in t$e bone
marro#
Major Clinical Characteristic
B12 deficiency ' Neurologic symptoms+ glossitis
8beefy red tongue9; gastrointestinal sym"toms
Folate deficiency ' &imilar to features abo!e+ but
#it$out neurological "roblems
aboratory !esting
<emogram
Mor"$ology
Bone marro# e0amination 8rare9
&erum B12
&erum folate
:t$er tests
"emogram Pattern in Megaloblastic Anemia
=BC 4/
<gb
MCV
PL, 4/
Peripheral #loo$ Morphology
-nisocytosis
Macro)o!alocytes
Possible megaloblasts
%iant and $y"ersegmented neutro"$ils 8P- "olys9
Possible granule deficient "latelets
#one Marro% Fin$ings
<y"ercellular
KKA-481 Mira Yulianti (01-107)
Macroovaloc
yte
RPl < 2
Polychromatop
hilic
Macrocyte
&P'()
Predominantly megaloblastic eryt$ro"oiesis
%iant granulocyte "recursors
4uclear)cyto"lasmic async$rony
Possible decreased megakaryocytes and nuclear
c$anges
*erum #+, an$ Folate Assays
Princi"le ' Com"etiti!e "rotein binding
radioimmunoassay
=as$ing to remo!e unbound radioacti!e labels
)scintillation counting
7esidual radioacti!ity is in!ersely "ro"ortional
to t$e amount of "atient>s B12 and folate
7esult determined by com"arison to standard cur!e
&"ecimen re.uirements
&erum "referred
/D,- "lasma acce"table
Fasting s"ecimen for folate
-!oid $emolysis for folate assay
&"ecimen storage
Protect from lig$t 8folate9
2)?@C for 1 $ours
)2A@C longer "eriods
&"ecimen "re"aration' boiled or e0"osed to an alkaline agent
7eference ranges
&erum B12 ' 1AA)6AA "g/mL
&erum Folate ' 1)15 ng/mL
Lo#er limit for B12 deficiency not #ell defined
(n untreated "atients #it$ folate deficiency
le!els are usually B1.A ng/mL
:t$er tests may be needed in borderline cases
&c$illing test
Crine formiminoglutamic acid 8F(%lu9' Increased in
B12 and folate deficiency
Crine/serum met$ylmalonic acid 8MM-9
&"ecific for B12 deficiency
/le!ated in B12 deficiency
Serum B
12
and Folate Assays
B
12
57
Co
IF
F
L
125
I
IF
L
F
125
I
F
125
I
B
12
B
12
57
Co
57
Co
B
12
Pts Vitamin B
12
F
Pts Folate
57
Co
57
Co-labeled cobalamin
125
I
125
I-labeled folic acid
IF Intrinsic factor
L
-lactoglobulin
KKA-481 Mira Yulianti (01-107)
!reatment
(ntramuscular inDections of !itamin B12 e!ery 1)1 mont$s
/ffects '
(ncreased reticulosits count in 3)6 days
<C, in reference range in 1)2 mont$s
:t$er 7BC "arameters return to normal
<y"ersegmented neutro"$ils disa""ear in 2 #eeks
Platelet count normal #it$in 6 days
KKA-481 Mira Yulianti (01-107)