MACROCYTIC ANEMIA

Rahmawati Minhajat
Tutik Harjianti
A. Fachruddin B

Div. of Hematology & Medical Oncology

Dept. of Internal Medicine, Medical Faculty
Hasanuddin University

Deficiency of Cyanocobalamin

B12 : all of it made from diet

A food ingredients may from animal.
Absorbtion : 5 ug / days
Cofactor at 2 important reaction in a body

Division of Hematology & Medical Oncology Dept. of Internal Medicine

The role of Cyanocobalamin

Methyl-Cobalamin is a cofactor for methioninesynthetase at rx change of homosystein

metyonin.
Adenosyl-Cobalamin is a cofactor at rx change
of methyl-malonyl CoA succinyl-CoA

Division of Hematology & Medical Oncology Dept. of Internal Medicine

Deficiency Cyanocobalamin
An important sign :
1. macrocytic Anemia
3. Level of Vit B12 <100 pg/ ml

sign

2. Peripheral blood smear:

macro-ovalocyte & hypersegmented neutrophil

Division of Hematology & Medical Oncology Dept. of Internal Medicine

Macrocytic

Normocytic
Division of Hematology & Medical Oncology Dept. of Internal Medicine

The Cause
1. Deficiency vit B12 (diet)
2. The decrease production of intrinsic factor
(Anemia perniciosa, post-gastrectomy)
2. The decrease absorbtion of vit B12 at the ileum
(Post-op, Crohn ds)
3. Helmynthyasis (tape-worm)
4. Deficiency Transcobalamin II

Division of Hematology & Medical Oncology Dept. of Internal Medicine

Physiology
Vit B12 come in from IT binding with intrinsic
factor (made from parietal mucosa gaster cell)
abs in ileum terminal by spesific receptor
come in to the plasma liver .
There are 3 protein transporter in the plasma :
Trans-cobalamin I, II & III (by leukocyte). Only
Trans-cobalamin II that can transport vit B12
into the cell.

Division of Hematology & Medical Oncology Dept. of Internal Medicine

Division of Hematology & Medical Oncology Dept. of Internal Medicine

Phatogenesis
Hepar consist 2.000 5.000 ug vit B12
Need : 3 5 ug / hari

Defs vit B12 will be happen in 3 years after no

more absorpsi.
Defs caused by diet less vit B12 vary rare
( vegetarian )

Example :

Gastrectomy the area produce factor

intrinsik will decrease
Over-growth bactery in intestinal
Reseksi ileum the area of absorpsi vit
B12 will decrease
Helmenthyasis
Crohns disease ileum destruction
the area of absorpsi vit B12 will decrease

Anemia Perniciosa
Often cause defs B12
Abnormality Auto-Imun herediter
Seldom show before 35 years old
Scandinavia / Eropa Utara
A black skin teenager, a hispanic woman

Anemia Perniciosa
Clinic illustration :
Likely anemia caused by defs vit B12,
- Gastritis atrophic
- Abnormal Auto-Imun ( rheumatoid arthritis
Graves disease, defs IgA )
- After several years some patient
Gastritis Atrophic => Carcinoma Gaster

CLINIC MANIFESTATION OF
DEFS. VIT B12
Megaloblastic anemia

May a hard anemia ( hematokrit < 10 % )

A change mucosa cell : glossitis, anorexia,
diare.
Neurologic disturb:
1. Perifer parestesi
2. Cerebral difunction

Lab. Abnormal
1. Megaloblastic Anemia
2. MCV between 110 140 fl (increase)
at some patients : MCV normal

3. Blood Perifer : anisocytosis &

poikilocytosis. Specif : macro-ovalocytes.

Blood Perifer
4.Morfologi eritrosit is abnormal
Likely Hemolytic Anemia
5. Hypersegmentation of neutrophyls
6. Decreased Reticulocyte amount

Bone Marrow Asp

In-efective Erythropoesis ( abnormally RBC
production)
erythroid hyperplasia ( as respons )
Abnormal megaloblastic Cell in BM and different
shapes :
* Large abnormal size,
* nuclear maturation & cytoplasm are not
synchronize.
Maturasi cytoplasm is normal,
DNA synthesis is bother
Myeloid : Giant cell (meta-myelocyte)

Other Abnormal Lab :

In-efective erytropoesis in BM may happen
destruction of erythroid cell that in the
development period increased level of LDH (
lactic-dehydrogenase ) and Bilirubin indirect

Diagnosis
1. Level of vit B12 serum is low
( normal : 150-350 pg / mL )
2. Schilling test ( for dx A Perniciosa /
the decrease absorpsi vit B12 oral )

THERAPY
*

Anemia Pernisiosa (oral absorpsi

disfunction)
Intra-muscular Inj. Vit B12 ( IM )
Dosis : 200 ug
1st week : every day (replacement tx)
2nd 4th week : every week
Once a month

Respons Therapy
Reticulocytosis 5 7 days.
Abnormalitas hematologic disappear after 2
months.