Anemia

NYOTO WIDYO A
Subbagian Hematologi-Onkologi Medik,
Bagian Ilmu Penyakit Dalam,
RSPAD GATOT SOEBROTO,
Jakarta

Hematopoiesis
IL-6 GM-CSF
BFU E

IL-1 IL-6 INF

CFU L

IL-1 IL-2

IL-2

CFC Mix
IL-6

Pro B

MGDF, TPO

IL-2

IL-4

GM-CSF
CFC E

CFC Bas CFC Eos CFC GM

Erithroblast

Myeloblast

CFU Meg

CFC TL

Pro Megacaryoblast

IL-4

CFC BL
IL-2

T Lymphoblast B

Lymphoplasmacytoid

Plasma cell

IL-6

IL-6

IL-6

GM-CSF

MGDF

IL-2

Visible Hb

IL-6

LAK NK
IL-2
IL-4
Proerythroblast
Promyelocyte
Mega
Normoblast :
B Centroblast
karyoblast T Immunoblast
Basophylic
Myelocyte
Polychromatophylic
B Immunoblast
Metamyelocyte Megakaryocyte
Orthochromatophylic
IL-12
IL-4
IL-11
T cell
Reticulocyte
Band
Centrocyte
Thrombocyte
Erythrocyte
Segmen
EPO

Maturasi

GM-CSF IL-3

CFU GM

EPO

Proliferasi dan Maturasi

Pluripotent stem cells

B cell

Erythropoiesis
Time to circulation of
red blood cells from
Stem cell in BM have
app.120 days
2.3 million red blood
cells produced every
second in human bone
marrow
138 million every
minute
18.4 billion between
now and lunch-time!
Main regulator is

Erythropoiesis: Growth
Factors
___________SCF____________
___________ IL-11___________
______________ IL-3___________________________
______G-CSF _____ _______ GM-CSF_______
_______IL-6_______ _______IL-4_______
_________EPO_________
_______IL-9_______

Quiescent
stem cell

Activated
stem cell

BFU-E

CFU-E

Erythrocyte

SCF = stem cell factor; IL = interleukin; G-CSF = granulocyte colony-stimulating

factor; GM = granulocyte - monocyte colony-stimulating factor; EPO = erythropoietin;
BFU-E = blast-forming units-erythroid; CFU-E = colony-forming units-erythroid
Gabrilove (2000)

Mechanism of action of
EPO
Increase in total RNA synthesis

Increase Transferrin receptors expression Increase iron

uptake
Increase Heme synthesis
Increase rate of transcription of and -globin gene
Increase Hemoglobin synthesis

In absence of EPO
Decrease synthesis of cytochromes, catalase, peroxidase
Rapid DNA cleavage apoptosis

IRON ABSORPTION

Ferrokinetik
Fe+2

DCyt-b

DMT1

Fe+3

Ferritin
TFR
Fe
Heme

Ferroportin

Hepaestin

Fe-transferin
SI
Hemosiderin

cytochrome
Apoferritin
Apotransferin

Hemoglobi
nNormal:
Foetal:

Hb F mengandung 2 pasang rantai dan (N > 95%),dan

Hb A2 mengandung 2 pasang rantai dan (N < 5%)

Dewasa:

Rantai Hb F () diganti Hb A1()

Hb F mengandung 2 pasang rantai dan (N < 1 %)
Hb A1 mengandung 2 pasang rantai dan (N > 95%)
Hb A2 mengandung 2 pasang rantai dan (N < 3.5%)

Intracellular site
protein (globins)
product
B=babies
A=adult

B A

Fe

Fe

Fe

Heme

Heme

Heme

HbF

HbA2

HbA1

Hemoglobi
involvements normal globin
nGenotype
Hb F
:

Hb A2
Hb A1

:
:

DNA inti mRNA Ribosome Globin

DNA Mitochondria mRNA Ribosome Heme
Cytosol Heme + Globin Hemoglobin
Fungsi globin dalam hemoglobin:

Mengikat oksigen
Fe

Fe

Fe

Heme

Heme

Heme

HbF

HbA2

HbA1

Definisi anemia
Keadaan dimana kadar hemoglobin

lebih dari 10% dibawah rerata nilai

normal
WHO:
Pria

< 13 gr%,
Wanita < 12 gr%, dan
Kehamilan 10 gr%.

Grading anemia
Hb
Ringan (mild)
10 mg/dL
Sedang (moderate) 8 <10 mg/dL
Nyata (marked) 6 <8 mg/dL
Berat (severe)
< 6 mg/dL
Digunakan dalam diagnostik laboratorium sebagai research cutof
Tidak dapat digunakan untuk batasan diagnostik klinis

Gejala umum dan khusus

anemia

Mekanisme

System/orga
n

Symptom

Penurunan
kapasitas
angkut oksigen

End arteries
Jantung
Respiratory
Neuromuscular
Hearing
Sighting

Pale (vasoconstriction)
Tachycardia, systolic ejection murmur, Forth gallop
Tachypneu, Exertional dyspneu
Faintness, Lack of concentration,
Tinnitus (ischemic)
Scotoma (edema papil)

Perdarahan

Haid
Feses
Hidung
Mulut

Menorhagia, Polymenorrhagia
Melena, hematoschezia
Epistaksis
Gusi berdarah

Atropi-Nekrosis
Mucosa

Tongue
Pharinx

Glossitis, hypotrophy papilla (B12, Folat, less in Fe

deficient)
Angina Vincent/dysphagia (Fe deficient)

Neuritis

Kaki/Tangan

Foot/Hand gloves periveral neuropathy (B 12 deficient)

Hemolisis
Intravascular

Urin

Hemoglobinuria: Reddish urine (PNH, DD/hematuria)

Hemosiderinuria: Blackish urine (Black water fever,
Malaria)

Hemolisis
Extravascular

Urin
Limpa

Urobilinogenuria with/without Brownish urine (bilirubinuria)

Splenomegali

Hati dan limpa

Hepato-splenomegali

Extramedullar

Klasifikasi dan terminologi

anemia
I.

Gangguan Produksi SDM

a. Proliferasi dan pematangan
1)
2)
3)
4)
5)

Inti Makrositik
Sitoplasma Mikrositik hipokrom
Defisiensi eritropoietin
Defisiensi ACTH
Defisiensi protein

Infiltrasi sel non eritroid kedalam sumsum tulang

c. Aplastik
II. Penghancuran SDM
a. Defect corpuscular:
b.

1)
2)
3)

Defisiensi enzim eritrosit:

Thalasemia
Hemoglobinopati

Defect extracorpuscular
III. Perdarahan
b.

Gangguan Produksi SDM

1.

Gangguan Proliferasi dan pematangan

a.

Inti (Makrositik):
1)

Normal megaloblastik:

2)

Abnormal megaloblastik:

b.

e.

Defisiensi Fe, Transferin (Protein transport)

Gangguan utilisasi Fe (MDS)
Gangguan re-utilisasi Fe (ACD, Thalasemia mayor)

Defisiensi eritropoietin

d.

Sindroma mielodisplasia (MDS)

Eritrolekemia (AML-M6)

Sitoplasma (Mikrositik hipokrom):

c.

Defisiensi: B12, Asam folat, Vit.A, Vit.C, Cuprum

Renal disease

Defisiensi ACTH
Defisiensi protein

Gangguan Produksi SDM

(lanjutan)
2. Infiltrasi sel non eritroid kedalam sumsum tulang
fibrosis, kanker, dll
3. Aplastik
Pure red cell aplasia (PRCA, e.g. thymoma)

Antibody erythropoietin
Antibody erythropoietin receptors

Hypoplastik marrow (Anemia aplastik)

Penghancuran SDM
a. Defect corpuscular:
1. Defect membrane
a.

Congenital
a.
b.
c.

b.

Erythropoietic Porphyria Congenital

Elliptocytosis herediter
Spherocytosis herediter (congenital hemolytic jaundice)

Didapat
a.
b.

Stomacytosis
Hypophosphatemia

2. Defisiensi enzim eritrosit congenital

a.

Pyruvate kinase deficient (< 13 g/gHb)

b.

Autosom recessive

Defisiensi G6PD (< 5 g/gHb)

X linked

3. Defect synthesis Globin

a.
b.

Thalasemia
Hemoglobinopati

Penghancuran SDM
(lanjutan)
b. Defect extracorpuscular
1.
2.
3.
4.

Hypersplenism
Immune hemolysis (AIHA, SLE, APS, PCH)
Complement sensitivated (PNH)
Mekanik: Penurunan shear rate
a.
b.

5.

Toksin:
a.
b.
c.

6.

Sistemik: CHF
Partial luas: TTP, KID, Vasculitis, Hemangioma, dll.
Obat-obatan: Sulfonamida, dll.
Metabolit: Uremia (HUS), Cyclosporin, dll.
Zat kimia: Bahan pewarna (Anilin), dll.

Infeksi:
a.
b.

Parasit: Malaria, Toxoplasma, dll.

Virus: CMV, Mycoplasma pnemoniae, Parvovirus, dll.

Penggolongan menurut
Morfologi volumetrik
Mikrositik
hipokrom
MCV < 80 fL
MCH 27 pg
MCHC < 30 g/dL

Normositik
normokrom Makrositik
80 100 fL > 100 fL
> 27 pg
> 27 pg
30 g/dL

30 g/dL

MCV= (Ht/Eritosit)x10 fL
MCH=(Hb/Eritrosit)x10 pg
MCHC=(Hb/Ht)x100 g/dL

Anemia mikrositik
hipokrom
Diagnostik:
Rerata volume eritrosit (VER) < 80 fL dan
Rerata konsentrasi hemoglobin eritrosit (KHER) < 30
g/dL atau
Rerata konsentrasi hemoglobin (HER) 27 pg/dL.
Penyebab:

Inefective metabolisme besi.

Hambatan pasokan, transport,

defisiensi enzim, dsb

Pembentukan hemoglobin abnormal:

hemoglobinopati,

Retikulosit
Rasio retikulosit =Hitung Retikulosit x 1000
Hitung Eritrosit
Indeks/koreksi retikulosit (Normal: 5-15 .);
Ht
Pria
: 42 x Rasio retikulosit
Ht
Wanita
: 39 x Rasio retikulosit

Hb
18
17
16
15
14
13
12
11
10

Ht
54
51
48
45
42
39
36
33
30

Rasio Retikulosit ()
Pria
Wanita
4.0
3.6
4.2

3.9

11.8
11.0
4.4

4.1

12.5
11.7
4.7

4.4

13.2
12.4
5.0

4.7

14.1
13.1
5.4

5.0

15.0
14.0
5.8

5.4

16.1
15.0
6.3

5.8

17.3
16.2
6.8

6.4

18.8
17.5
20.5
19.1

FLOW CHART ANEMIA MIKROSITIK

HIPOKROM
Anemia
MCV<80fl & MCHC<30g/dL or MCH 27 pg/dL

Indeks retikulosit <10

Indeks retikulosit 10-15 Indeks retikulosit >15

SI/IBC, Transferin, Feritin

Normal/Tinggi

Elektroforesis hemoglobin
Normal

Defisiensi Fe

Dalam terapi Fe ?

BMP

Abnormal
Hemoglobinopati

Pasokan, Absorpsi ?
Hemolitik ?

Gangguan metabolisme
Fe
Mielodisplasia (MDS)
Anemia of Chronic Diseases (ACD)

Thalasemia

Anemia Defisiensi Besi

Serum feritin <20 ng/mL, atau
Indeks saturasi transferin (IST)< 15%

(syarat: TIBC within normal limit)

SI
IST
* 100%
TIBC

Normal limit:
SI
50 -150 g/dL
IBC
250-410 g/dL
Serum feritin 20-200 ng/mL,
excess >400 ng/mL

Defisiensi Besi
Defisiensi besi ringan

Serum iron 50 g/dL

Indeks saturasi transferin (IST) 15%
IBC within normal limit or transferin within normal
Serum feritin < 20 ng/mL.

Defisiensi besi berat

Serum iron <50 g/dL

Indeks saturasi transferin (IST) 15%
IBC within normal limit or transferin within normal limit
Serum feritin < 20 ng/mL.

Defisiensi transferin ringan

Serum iron 50 g/dL

Indeks saturasi transferin (IST) >15%
IBC below normal limit or transferin below normal limit
Serum feritin 20 ng/mL.

Defisiensi transferin berat

Serum iron < 50 g/dL

Indeks saturasi transferin (IST) >15%
IBC below normal limit or transferin below normal limit
Serum feritin 20 ng/mL.

IST

SI
* 100%
TIBC

Koreksi defisiensi besi

serum
Untuk menaikkan Hb sebesar 1 gr/dL dibutuhkan Fe

endogen 2,5 mg/kgBB

Kebutuhan initial Fe:

Fe = ( Kadar Fe serum x 0,2 x BB) mg, atau

Fe = (Hb x 2,5 x BB) mg

Iron Dextran max. 1,5 mg/kgBB/day

Jectofer 75 mg/2mL amp.

Cara 75 mg/deep im

Iron Sucrose

Venofer 100 mg/amp

Cara infusi 100 mg in 100cc NS 1jam

Anemia tersering pada

kehamilan
Makrositer (Normal Megaloblastik)

akibat defisiensi asam folat,

Suplemen asam folat 0,4 mg/hari dan

Suplemen vitamin B12 50 mg/hari mulai
sejak awal kehamilan.

Mikrositik hipokrom akibat defisiensi Fe,

Suplemen Fe 30-60 mg/hari mulai

kehamilan 18-20 minggu.

Anemia makrositer
Diagnostik: MCV > 100 fL
Penyebab:
Inefective

metabolisme vitamin B12

dan/atau asam folat.
Hambatan:
Pasokan vit.B12 dan/atau asam folat,
Transport vit.B12 dan/atau asam folat, atau
Pengikatan vit.B12 dan/atau asam folat
oleh reseptornya (Defisiensi enzim).

FLOW CHART ANEMIA MAKROSITER

Anemia
MCV > 100 fl

Indeks retikulosit <10 Indeks retikulosit 10-15 Indeks retikulosit >15

Kadar B12 & Folat

Defisiensi Folat

Analisis gizi
Baik

Defisiensi B12

Perdarahan/Hemolisis ?

Normal

Schilling test

TIDAK

YA

BMP

Kurang TerkoreksiTidak terkoreksi

Megaloblastik Non Megaloblastik

Malabsorpsi

Def. IntrinsikMalabsorpsi

Inapropriate diet

Cincin sideroblastik

Hipoplastik
mieloptisis
Kongenital/Obat

FLOW CHART ANEMIA NORMOSITIK

NORMOKROM
Anemia
MCV 80-100 fL and MCHC 30 g/dL or MCH 27 pg/dL

Indeks retikulosit <10

Indeks retikulosit 10-15

Abnormal
Hambatan
Produksi/Pematangan

BMP

Normal
Anemia hemolitik/def.Fe
dalam terapi ?
Periksa ACTH

Indeks retikulosit >15

Kehilangan/Penghancuran Berlebihan
Periksa: Bilirubin indirek, LDH

Normal

Tinggi

Perdarahan
?

Anemia Hemolitik

Tidak

Ya

Periksa urin

Infiltrasi Keganasan
Hipoplasia
SSTL
Cincin sideroblastik ?

Negatif
Tes coombs, C3/C4
Anti dsDNA

Positif
AIHA Primer or Secunder
Negatif
Defect Intra corpuscular

Positif Hb/
hemosiderin

Hemolisis
Hemolisis
Ekstravaskular Intravaskular
Defect Extra corpuscular
Mekanik, Toksin, Infeksi

Anemia normositik
normokrom
Diagnostik:
MCV

80-100 fL dan
MCH > 27 pg atau MCHC 30 g/dL
Penyebab:
Kegagalan

distribusi.
Hambatan produksi,
Kehilangan/Destruksi berlebihan.

Anemia Hemolitik Auto

Immun
Primer: Idiopatik
Sekunder:
Terjadi akibat adanya kelainan/ penyakit lain seperti:
Induksi obat atau bahan kimia
Kelainan limfoproliferatif
Kanker
Infeksi (HIV, Mycoplasma pnemoniae, Parvovirus, dll)
Penyakit Autoimmun lain (SLE, APS, dll)

Kriteria Diagnosis AHAI

Direct Coombs test positif (C3b &/ anti IgG pada eritrosit).
Perexclusionam menyingkirkan kemungkinan AHAI

sekunder:

Anamnesis obat-obatan, alkohol, bahan kimia (Occupational

disease), adakah keganasan ?,
Pemeriksaan serologi virus dan bakteria misalnya Dengue,
CMF, EBV, HIV, Rubella,
Pemeriksaan ACA untuk mengetahui adanya Sindroma Anti
Fosfolipid (APS),
Pemeriksaan Rematoserologi, C3 dan C4, ANA, Anti dsDNA
(Penyakit Auto Immun),
Pemeriksaan combs apakah ada IgG/IgM atau C3b pada
eritrosit dan/atau antibody terhadap eritrosit, jenis reaktifitas
cold type jika bereaksi pada suhu 20oC
Pemeriksaan sidikan hati, limpa, KGB mediastinum dan para
aorta (Limfoma Non Hodgkins),
Pemeriksaan Immunoelektroforesis protein (Penyakit proliferasi
sel B limfosit atau plasma),
BMP Aspirasi dan Biopsi untuk menilai adanya Penyakit
limfoproliferasi non sekretorik.

Defect corpuscular
Defisiensi enzim eritrosit (G6PD, dll)
Pemeriksaan yang diperlukan:

Pemeriksaan enzim G6PD or GSH eritrosit intrasel.

Hemoglobinopati
Thalasemia, Sickel cels anemia, dll
Pemeriksaan yang diperlukan:

Morfologi mikroskopik eritrosit,

Pemeriksaan Sugar Water Test (SWT), dan
Elektroforesis Hb.

Herediter sferositosis
Pemeriksaan yang diperlukan:

Morfologi mikroskopik eritrosit, dan

Resistensi osmotik.

Defect corpuscular
PNH
Pemeriksaan yang diperlukan:

Pemeriksaan Hb urin pada urin pagi pertama dan

Acid test (HAM).

Porfiria
Pemeriksaan yang diperlukan:

Pemeriksaan Porfirin,
Pemeriksaa Fosfatidil-inositol.

Defect Extra corpuscular

Manifestasi dapat:
Tanpa atau disertai AHAI.
Tanpa atau disertai Defect Intracorpuscular.
Penyebab:

Mekanik:

Toksik:

Obat-obatan: Sulfonamida, dll.

Metabolit:

Penurunan shear rate sistemik (CHF) atau

Penurunan shear rate partial luas (TTP, KID, vaskulitis,
hemangioma, dll)

Sindroma Hemolitik Uremik (Gagal ginjal),

Siklosporin, dll.

Zat kimia: Bahan pewarna (Anilin), dll.

Infeksi mengenai eritrosit:

Parasit: Malaria, Toxoplasma dll,

Virus: CMV, Mycoplasma pnemoniae, Parvovirus dll.

Thalasemia
Thalasemia : kegagalan produksi globin rantai
Thalasemia : Present Hb H or Barts
Single gene
Double gene
Genotype Hb Barts :
Triple gene
Genotype Hb H
:
Thalasemia : kegagalan produksi globin rantai
Heterozygot: defect gene (allele) single haploid
Homozygotes: defect gene (allele) diploid
Thalasemia : defect gene dan
Heterozygot: defect gene and(allele) single haploid
Homozygotes: defect gene and(allele) diploid

q 11

q 16

Triple gene deletion

Double gene deletion

Hb F :
Hb A2 :
Hb A1 :

Single gene deletion

Genotype globins

Homozygote

Heterozygote

Homozygote

Heterozygote

Intracellular
site protein
(globins)
product
B=babies
A=adult

B A

Globin abnormal
Abnormal hemoglobin:

Thalasemia
Insufficient of normal
globin
Hb Barts ()
Hb H ().

Hemoglobinopati
Changes amino acid in
normal globin

Hb
Hb
Hb
Hb
Hb
Hb

C,
D,
E,
G,
S, sickle cell
variant

Thalasemia
Delesi

Anemia

HbF HbA2 HbH

Heterozygote

Ringan

< 5% > 3.5%

Homozygote

SedangBerat

>
85%

> 3.5%

Heterozygote

Ringan

> 5%

< 1%

Homozygote

SedangBerat

100
%

Absent

single gene

Non

double gene

Ringan

<
< 2.5%
0.5%

Triple gene deletion Sedang

*triple
gene

<
< 2.5% Presen
0.5%
t

Mix

<0.5

Sedang

>3%

Presen

Clinical form
Thalasemia
Silent carrier (no hematologic or clinical symptom)
Trait
HbH disease
Unusual form

Thalasemia MDS
Thalasemia and Mental retardation syndromes
Thalasemia Associated with Structural Variants

Clinical form
Thalasemia
Mayor (Homo/Heterozygote) :
Transfusion dependent anemia
Intermedia (Homo/Heterozygote) :
Transfusion Independent anemia
Minor (Heterozygote) :

Asymptomatic

Minima (Heterozygote) :
Silent carrier (no hematologic or clinical symptom)

Dampak thalasemia pada

kehamilan
Fetal hanya membentuk:
Hb F mengandung 2 pasang rantai dan (N > 95%),
Hb A2 mengandung 2 pasang rantai dan
Thalasemia
; ; ;
;

Single genes
Double genes
Triple genes
Homozygotes

+++ +++
++ ++

+
+

+
++
+++

++
+
++ ++
+++ +++

Erythroblastosis foetalis
Hemolytic anemia of the foetus
Frequently caused by transplacental transmission of maternal
antibody

Immunogenisitas
Eritrosit
ABOEritrosit
& Rhesus
Serum
Reagen

Reagen
Ag

Blood
Type

Ab

AgA

AgB

None

A&B

A &B

None

AB

AbA

AbB

Ab-Rho

ABO

Ag-Rho

Rhesus

Rho

None

Rh+

None

Rho+

Rh-

Antibodi dan antigen

eritrosit
Blood type
Antibody
Antigen
A
B

B
A

A and B
Rho(C,D,E)

None
None

None
Kell (K)

Rho(C,D,E

Dufy (Fy)
hr (c,e)

IgG labeled erythrocyte

C3b labeled

erythrocyte

)
None
None
None
?
?

B
A
O
RhRh+
KFyhrc,e -

Incompatibilitas ABO &

Rhesus (erythroblastosis
Transfusi darah
Ibu & Janin
foetalis)
Resepien
Dono O A
r
O

-/+

Janin

AB

-/
+

-/+

AB

Rh+

Ibu O A

AB

AB

Rh+

Rh-

Rh+

Rh-

Rh
+

-/+

Rh-

Rh- Donor
-/+
Antibodi:
Antigen: Donor

Resepien
Resepien

Antibodi: Ibu
Antibodi: Janin

Janin
Ibu

Program kelasi besi

Target feritin serum <1000 ng/mL.
Desferroxamine (Desferal vial 500 mg); for
im (max.adult 2gr, child 1gr), or
sc slow continuous infusion over 12h at night
iv infusion max.rate 15 mg/kgBW/h
Starting dose 500 mg increasing until 24h of

iron urin excression has plateau.

Daily dose
< 2000
25mg/kgBW
Feritin 2000-3000
35 mg/kgBW
>3000
40 mg/kgBW

Potentiation chelatable DFO

Vitamin C
Recommended

only in patient with not

affected by myocardiopathy
50 mg/day for <10 yrs old
100 mg/day for 10 yrs old

Gene function
(Suppressor genes)
Protein/Amino acid

(Proto-oncogenes)
Control
Protein/Amino acid

Inducers
Hyperplasia:
Control proliferation
Inducers proliferation
Hypoplasia:
Control proliferation
Inducers proliferation

Cells Proliferation
Cells Diferentiation

Kanker
Sel kanker

Sel yang sifat pertumbuhannya berubah

menjadi tak terkendali
Onkogen
Gen

sel tumor
Muasal
Proto-onkogen: gen yang akan mengalami
penambahan atau relokasi material genetik (amplifikasi).
Gen supresor tumor atau gen anti tumor: gen yang
akan mengalami kehilangan material genetiknya (LOH).

Fungsi

Produk proteinnya akan mengendalikan pertumbuhan

(maturasi dan diferensiasi) dan replikasi sel tumor

Proto-onkogen changes
Gen supresor tumor

Onkogen

Leukemia
Generalized neoplastic disorders of the

blood forming tissues, primarily those of

the leukocytic series
Marked proliferation
Acute

Minimal diferentiation/maturation

Chronic
Normal diferentiation/maturation

Cyto-morphology diagnoses by Bone

marrow aspirate
Blast > 30%
Blast 50%
ME ratio 1

Blast > 50%

ME ratio > 1

PAS

Negative

Negative

Positive

Positive
M6/M7

M0/ALL
AP-L

SBB/POX

Blast with blebs,

megakaryocytic
fragments are
seen in peripheral
blood

Negative
Positive
B cell

M0
ALL

NSE

+
T cell

M1 Blast > 90% (Blast + myeloid)

>3%

Blast < 90% (Blast + myeloid),

M2 and
monocytoid < 20% myeloid

30%

M3

Promyelosit > Blast

100
%

monocytoid > 20% myeloid,

M4 and
Monosit perifer > 5000/mm3

80%

M5 monocytoid > 80% myeloid,

and
a Blast > 80% monocytoid

90%

monocytoid > 80% myeloid,

Subclassification of ALL
Cell size

chromatin

nucleoli

cytoplasm

L1

Homogenous
Small

Homogenous

Rare

Minimal
No granules

L2

Heterogeneou
s
Larger

Heterogeneou
s

More present

Often moderately
Some deep
basophilic

Homogenous
Larger

Finely
homogenous
stippled

Moderately
Prominent one
Deep basophilic
or more
and prominent
vesicular
vacuolation

L3

Hypothetical scheme of lymphocyte

differentiation


Terima kasih

Immunophenotype
Positive

Negative

M0
M1 HLA-DR, CD13, CD15, CD33, CD34,
CD65
M2 HLA-DR, CD13, CD14, CD33, CD36
M3 CD13, CD33, CD65

CD15, HLADR

M4 HLA-DR, CD13, CD14, CD33

M5 HLA-DR, CD13, CD14, CD33
M6 HLA-DR, CD14, CD36, CD41/CD61
M7 CD42, CD41/CD61
L1

CD33

L2

CD33