Anemia

Diagnosis dan
Tatalaksana
Dimmy Prasetya

Hematopoiesis
GM-CSF IL-3

CFU GM

BFU E

IL-1 IL-6 INF

IL-2

CFC Mix
IL-6

Pro B

MGDF, TPO

IL-2

IL-4

IL-4

GM-CSF
CFC Bas CFC Eos CFC GM CFU Meg

Erythrocyte

Segmen

IL-12

Thrombocyte

T cell

LAK

B Centroblast

B Immunoblast

IL-6

IL-11
Band

IL-4

IL-2

IL-6

Visible Hb

EPO

Reticulocyte

T Lymphoblast B

Mega
karyoblast T Immunoblast

Megakaryocyte

CFC BL
IL-2

IL-2

IL-6

Myeloblast

MGDF

Erithroblast

CFC TL

Pro Megacaryoblast
GM-CSF

CFC E

Proerythroblast
Promyelocyte
Normoblast :
Basophylic
Myelocyte
Polychromatophylic
Metamyelocyte
Orthochromatophylic

Maturasi

CFU L

IL-1 IL-2

IL-4

IL-6

IL-6 GM-CSF

EPO

Proliferasi dan Maturasi

Pluripotent stem cells

Centrocyte

Lymphoplasmacytoid

Plasma cell

B cell

NK

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

Pendekatan diagnosis
1. Memenuhi kriteria anemia
2. Derajat anemia
3. Jenis anemia
4. Penyakit dasar
5. Tatalaksana

Diagnosis
WHO:
Pria < 13 gr%,
Wanita < 12 gr%, dan
Kehamilan 10 gr%.

Derajat anemia

Ringan (mild)
Sedang (moderate)
Nyata (marked)
Berat (severe)

Hb
10 mg/dL
8 <10
mg/dL
6 <8 mg/dL
< 6 mg/dL

Digunakan dalam diagnostik laboratorium sebagai research cutof

Tidak dapat digunakan untuk batasan diagnostik klinis

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

b. Infiltrasi sel non eritroid kedalam sumsum tulang

c. Aplastik
II. Penghancuran SDM
a. Defect corpuscular:
1) Defisiensi enzim eritrosit:
2) Thalasemia
3) Hemoglobinopati

b. Defect extracorpuscular
III. Perdarahan

Gangguan Produksi SDM

1. Gangguan Proliferasi dan pematangan
a. Inti (Makrositik):
1) Normal megaloblastik:

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

2) Abnormal megaloblastik:

Sindroma mielodisplasia (MDS)

Eritrolekemia (AML-M6)

b. Sitoplasma (Mikrositik hipokrom):

Defisiensi Fe, Transferin (Protein transport)

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

c. Defisiensi eritropoietin

Renal disease

d. Defisiensi ACTH
e. 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. Erythropoietic Porphyria Congenital
b. Elliptocytosis herediter
c. Spherocytosis herediter (congenital hemolytic jaundice)

b.Didapat
a. Stomacytosis
b. Hypophosphatemia

2. Defisiensi enzim eritrosit congenital

a.Pyruvate kinase deficient (< 13 g/gHb)
. Autosom recessive

b.Defisiensi G6PD (< 5 g/gHb)

. X linked

3. Defect synthesis Globin

a.Thalasemia
b.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. Sistemik: CHF
b. Partial luas: TTP, KID, Vasculitis, Hemangioma, dll.

5. Toksin:
a. Obat-obatan: Sulfonamida, dll.
b. Metabolit: Uremia (HUS), Cyclosporin, dll.
c. Zat kimia: Bahan pewarna (Anilin), dll.

6. Infeksi:
a. Parasit: Malaria, Toxoplasma, dll.
b. Virus: CMV, Mycoplasma pnemoniae, Parvovirus, dll.

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

Extramedullar
hemopoesis

Hati dan limpa

Hepato-splenomegali

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

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

30 g/dL

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

Wanita :

Ht Rasio retikulosit
x
42
Ht
xRasio retikulosit
39

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 MAKROSITER

Anemia
MCV > 100 f

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

Kadar B12 & Folat

Defisiensi Folat

Defisiensi B12

Analisis gizi

Schilling test

Baik

Perdarahan/Hemolisis ?

Normal

TIDAK

YA

BMP

Kurang TerkoreksiTidak terkoreksi

Megaloblastik Non Megaloblastik

Malabsorpsi

Def. Intrinsik Malabsorpsi

Inapropriate diet

Cincin sideroblastik

Hipoplastik
mieloptisis
Kongenital/Obat

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 MIKROSITIK

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

Indeks retikulosit <10

Indeks retikulosit 10-15 Indeks retikulosit >15

SI/IBC, Transferin, Feritin

Normal/Tinggi

BMP

Defisiensi Fe

Elektroforesis hemoglobin
Normal

Abnormal

Dalam terapi Fe ?

Hemoglobinopati

Pasokan, Absorpsi ?
Hemolitik ?

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

Thalasemia

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,

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

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 karena Perdarahan

1. Perdarahan akut :

Contoh :
Pasca persalinan
Perdarahan Uterus Abnormal
Berakibat pada hilangnya volume darah
Syok hipovolemik
2. Perdarahan kronis
Saluran makan
Jalan lahir
Hilangnya zat besi
Anemia def. besi

SEVERITY

Initial steps in the management of upper gastrointestinal bleeding

Airway protection
Airway monitoring
Endotracheal intubation (if indicated)
Hemodynamic stabilization
Large bore intravenous access
Intravenous fluids
Red cell transfusion (for symptomatic anemia)
Fresh-frozen plasma, platelets (if indicated)
Consider erythropoeitin
Nasogastric oral administration
Large bore orogastric tube/lavage
Clinical and laboratory monitoring
Serial vital signs
Serial hemograms, coagulation profiles, and chemistries (as clinically indicated)
Electrocardiographic monitoring
Hemodynamic monitoring (if indicated in high-risk patients)
Endoscopic examination and therapy

Preparation of blood components

from whole blood
Whole blood
Leucodepleted
Cellular components

Fresh plasma

Fresh frozen plasma

Red cells
Platelets

Cryoprecipitate

Cryosupernatant

Factor VIII
Fibrinogen

Albumin
Immunoglobulin
etc

Indications for red cell transfusions

acute bleeding
GI bleed, trauma, surgical bleeding, obstetric haemorrhage

impaired production
neonates
bone marrow disorders
Life long transfusion thalassaemia, some sickle cell disease patients
leukaemia, myelodysplasia, aplastic anaemia

following chemotherapy

Thresholds for red cell transfusion

Acute bleeding >1L and further bleeding

anticipated, maintain Hb 9-10 g/dL
Perioperative blood loss and critically ill
patients maintain Hb 8-9 g/dL (possible
exception- MI and unstable angina)
Traditional cut of for transfusing where
Hb<10 is no longer considered
appropriate.

Indications for platelets

transfusions
decreased production
bone marrow disorders
chemotherapy related - commonest reason

increased destruction
impaired function
congenital
drug-related e.g aspirin

Thresholds for platelet transfusions

Prophylactic
Stable patients plat. counts <10 x 109/L
Sepsis
<20 x 109/L
Invasive procedures eg central lines, LP aim for plat count
>50
Surgery - aim for >100

Acute Bleeding
maintain platelet count around 50 -100

Monitoring of transfused
patient
Symptoms and signs of
transfusion reaction
Pyrexia > 1oC
Flushing
Urticaria
Rigors
Restlessness
Tachycardia

Anxiety
Pruritis
Palpitations
Dyspnoea
Headache
loin pain

Terima kasih