LOGO

Gangguan Eritrosit: Anemia

dr. Bastiana SpPK

 Gangguan Eritrosit LOGO

Anemia

Polisitemia

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 ANEMIA LOGO

Definisi Anemia:
Sindroma klinis yang disebabkan penurunan massa
eritrosit total dalam tubuh.
Keadaan dimana massa eritrosit dan atau massa
hemoglobin tidak dapat memenuhi fungsinya untuk
menyediakan oksigen bagi jaringan tubuh
Penurunan di bawah normal kadar Hb, hitung
eritrosit, dan hematokrit

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 ANEMIA LOGO

Penurunan Hb dan Hct :

< batas bawah 95% interval referens
dari kelompok usia, jenis kelamin
dan lokasi geografis (ketinggian)

Hb<12-14 g/dl ; (Hct <36-41%),

Anemia
Hb<7g/dl ! symptom (+)
Akut: hipovolumia (pucat,
ggn penglihatan, syncope, tachycardia) ;
Kronis: tissue hypoxia (fatique, dyspnea,
Headache, angina)

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ANEMIA symptoms / syndrome LOGO

Hb
PCV Hypoxia Otak , Otot
RBC
Kompensasi :
- heart rate tachycardia flow rate
cardiomegaly heart failure
- blood flow priority (pallor)
- RBC 2,3-DPG content O2 dissoc.curve
shift to the right O2 release to the
tissues .

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Klasifikasi Anemia LOGO

Berdasarkan patofisiologi:
I. Kegagalan produksi sel darah merah:
A. Gangguan sel induk hematopoesis
! Anemia Aplastik
B. Gangguan sintesis DNA
! Anemia Megaloblastik
C. Gangguan sintesis Hemoglobin (Hb)
! Anemia Defisiensi Besi, Thalasemia
D. Gangguan sintesis eritropoetin
! Anemia karena GGK

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 Lanjutan..anemia berdasarkan patofisiologi LOGO

E. Gangguan karena mekanisme lain:

! Anemia karena penyakit kronis,
! anemia sideroblastik
! Anemia karena infiltrasi sumsum tulang

II. Peningkatan destruksi sel darah merah:

! Anemia Hemolitik
III. Kehilangan darah (Blood Loss)
! Anemia karena perdarahan akut

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 Anemia LOGO

Anemia berdasarkan morfologi

Anemia sec. morfologi eritrosit, dilihat dari:
- ukuran dan warna di bawah mikroskop atau
- indeks eritrosit (MCV, MCH, dan MCHC)

- Kriteria Ukuran (size): Normositik, Mikrositik,

Makrositik
- Kriteria Warna (pucat): Normokromik,
Hipokromik

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Cara Mengetahui Ukuran eritrosit: LOGO

* membandingkan dengan inti sel limfosit kecil (di

bawah mikroskop) :
ukuran sama = normositik
lebih kecil = mikrositik
lebih besar = makrositik

* Menghitung MCV (Mean Cell Volume)

MCV= PCV/Ery X 10 (fL)
(1 fL=10-12L= 1m3)
N : dewasa = 80-100 fL , di bawah 1 thn = 76- 86 fL
MCV : normositik , mikrositik, makrositik

* Eritrosit dengan variasi ukuran yang abnormal!

anisositosis

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Bandingkan ukuran sel eritrosit dengan inti limfosit LOGO

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 LOGO

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 LOGO
Perhatikan Warna sel eritrosit :

- Bandingkan diameter central pallor(CP)

dengan diameter sel eritrosit tersebut .

- Normal, bentuk sel eritrosit adalah seperti cakram

bikonkaf (biconcave disk)
pada hapusan darah tepi terlihat bulat, 7-8
dengan area central pallor di bagian tengah

CP 1/3 Eri = normokromik

CP> Eri = hipokromik

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Eritrosit dengan central palor (CP) LOGO

Bandingkan diameter CP dengan diameter sel eritrosit

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 LOGO

- Warna, dapat diketahui juga dari MCH (Mean Cell Hb)

MCH= Hb/RBC x 10 (pg)
Dewasa: MCH=27-32 pg, Anak-anak: MCH=23-31 pg
(1pg=10-12g=1g)

MCH normal normokromik

MCH < normal hipokromik

- MCHC (Mean Cell Hb Concentration) :

MCHC=Hb/PCV x 100 (g/dL)
Normal: MCHC = 32-36 g/dL

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 Klasifikasi Anemia secara morfologi LOGO

1. Anemia Hipokromik-Mikrositik.

Anemia Normokromik-Normositik
2.

Anemia Makrositik
3.

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 LOGO

Anemia hipokromik- Anemia Anemia makrositik

mikrositik normokromik-
normositik

1 2 3
Contoh: Contoh: A. Megaloblastik,
- Anemia - Anemia pasca contoh:
perdarahan akut - Anemia defisiensi
defisiensi Fe - Anemia aplastik Folat,
- Thalasemia - Anemia hemolitik - Anemia defisiensi
- Anemia akibat - Anemia akibat vitamin B12
Penyakit Kronik penyakit kronik B. Nonmegaloblastik
- Anemia pada GGK contoh:
- Anemia - Anemia pada - Anemia pd peny.
sideroblastik mielofibrosis Hati kronis
- dll - Anemia pd
hipotiroid, dll

MCV <80 fl; MCH MCV 80 -95 fl MCV > 95 fl

<27 pg MCH 27-34 pg

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Hipokromik-Mikrositik LOGO

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Normokronik-normositik LOGO

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 Makrositik LOGO

makrosit-oval
(Anemia megaloblastik ditandai oleh makrosit oval ini)

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Pendekatan diagnostik Anemia: LOGO

Anamnesis:
onset /bleeding tendency / routine
medicinal / occupation / hobby / travel
history / family / diet / GI symptoms /
menstruation cycle / history of previous
pregnancy-delivery / alcohol consumption ,
etc

Pemeriksaan fisik :
conjunctiva & lips (pallor) / mouth
(cheilosis) / tongue (glossitis) / gum / nails
(koilonychia) , hair (signa de bandera,
alopecia) , jaundice , petechiae , liver &
spleen , lymphenodes ,rectal / vaginal
toucher , feet (ulcer,arthritis)

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 LOGO

Pemeriksaan Laboratorium
- CBC (complete blood count ) to confirm
anemia (Hb, PCV, RBC) & the type of anemia
(MCV; MCH; MCHC), RDW
- Reticulocyte count reflects marrows responses .
- PBS : to look for the RBCs shape and any abnormalities of
RBCs besides the other blood cell lines
- Iron status ( Serum Iron ,TIBC, % Transferrin
saturation , Iron storage )
- Blood chemistry ( direct/total bilirubin,LDH
and stool examination for occult blood test , etc) .
PBS: Pheripheral blood smear

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Lanjutan. Pendekatan Doagnostik LOGO

- Radiological examinations ( Chest X-ray,

USG , MRI )
- Cardiological examinations (EKG,Treadmill,
Echocardiography)

Notes ! :

- First confirm Anemia ( Hb , PCV , RBC )

- Classify the anemia (MCV, MCH, MCHC)
- Causes of anemia

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 LOGO

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Anemia Hipokromik-Mikrositik LOGO

- Setiap kondisi yang menimbulkan gangguan

sintesis Hb ! gambaran hipokromik mikrositik
- Anemia Defisiensi Besi !penyebab tersering
dari anemia Hipokromik-Mikrositik
- Perhatikan penyebab lain (DD=diff diagnosis)
sebelum mendiagnosis Anemia def. besi, spt:
- anemia akibat penyakit kronis
- Thalasemia
- anemia Sideroblastik, dll

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 LOGO

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 ANEMIA DEFISIENSI BESI LOGO

Definisi:
Anemia yang timbul akibat kosongnya cadangan besi
tubuh! besi utk eritropoeisis ! pembentukan Hb
Anemia def. Fe, ditandai dgn:
- anemia hipokromik mikrositik
- besi serum
- TIBC (Total Iron Binding Capacity)
- Saturasi transferin
- Feritin serum
- Pengecatan Besi sumsum tulang negatif
- Respon terhadap pengobatan dengan preparat Fe

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 LOGO

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Faktor Penyebab (Etiologi) LOGO

I. Keseimbangan negatif Fe (Negative Iron

balance):
- Asupan Fe
(inadequate diet , impaired absorption)
- Fe loss
(GI bleeding, excessive menstrual flow,
bleeding diathesis)
- demands
(infancy, pregnancy, lactation)

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Lanjutan.Faktor Penyebab LOGO

II. Inadequate presentation to erythroid

precursors:
- atransferrinemia
- Anti TrfR Ab

III. Abnormal Fe balance :

- Aceruloplasminemia
- Autosomal dominant hemochromatosis
( mutations in ferroportin )

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Patogenesis desifisiensi Fe LOGO

3 pathogenetic factors:
- Impaired Hb synthesis (consequence of
reduced Fe supply)
Transferin saturation< 16% !inadequate Fe-supply to
marrow Hb contents of RBC hypochromic &
microcytosis
- Generalized defect in cellular proliferation
- Fe-deficient oxidative damage to the red cells
membrane RBC deformability RBC viability
RBC destruction especially in spleen reduced
RBC survival

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Status besi tubuh: LOGO

Serum Iron = SI
Total Iron Binding Capacity (TIBC)
% Transferrin Saturation = SI/TIBCx100%
Simpanan besi (Iron storage):
- Hemosiderin produk degradasi feritin yang tidak
larut dalam air mayoritas tdd aggregat kristal ferric
oxyhydroxide, FeOOH (di Hepar danSutul dideteksi
dengan biopsi/aspirasi dan pengecatan besi
(prosedur invasif)

- Ferritin kompleks garam Fe3+dan apoferitin yang

larut dalam air, dengan jumlah yang sangat kecil di
serum.
(dideteksi dengan metode imunoasai)

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 LOGO

Kandungan besi tubuh = 35-50 mg/kgBB:

80% - Fe fungsional, sebagai heme-Iron
(65% Hb, myoglobin, enzim
heme : cytochrom-C,A,A3,B,
catalase , peroxidase)
- Non-heme-Fe (sebagian kecil)
20% - simpanan besi / Iron storage (ferritin,
hemosiderin)
hanya 15% pada wanita
0.2% - circulating (terikat padaTransferrin)

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 LOGO
Iron Cycle in the body :
Fe-diet as heme-Fe (Hb, myoglobin,
enzyme-Fe), 5-35% adsorbed
from animal/meat sources ,
adsorbed easily .
as non-heme-Fe (vegetables ,
legumes), 90% of diet-Fe but
only 2-20% of it absorbed
depends on the iron-status and
the ratio of Enhancer:Inhibitor

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 LOGO

Enhancers (zat yang menstimulasi

penyerapan (absorbsi) :
Ascorbate, Cytrate, organic acids / other
amino acids , by reducing Fe3+ to Fe2+.

Inhibitors (zat yang menghambat absorbsi) :

Carbonate, Phytate, Tannins, Phosphate,

Oxalat chelate Non-heme-Fe
unabsorbable

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 LOGO

Bahan makanan yang menghambat absorbsi

besi non heme (Non-heme Iron) :
- Phytate (dari legumes, sayuran)
- Tannin & Polyphenol (dari teh, kopi, wine,
coklat )
- Phosphate/phosphoprotein dari kuning telur
- Minerals (Ca, Zn, Cd)
- Tetracycline yang bereaksi dengan Fe
menghambat absorbsi

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Siklus Fe dalam tubuh : LOGO

Diets Iron duodenum / proximal jejunum .

Iron from gut released into circulation , bound to
transferin distributed to bodys organ / tissues( to
bone marrow as a part of heme / Hb ) circulate inside
red blood cells with blood flow

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The development of IDA LOGO

Stage-1 (prelatent Fe-deficient):

- progressive loss of storage-Fe
- bodys Fe reserve is still sufficient to
maintain both the transport and functional
compartment , so RBC development is
still normal .
- peripheral blood picture is normal , no
symptoms of anemia , but ferritin is .

*IDA= Iron Deficiency Anemia

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 LOGO

* Stage-2 (latent Fe-deficient)

- Exhaustion of storage-Fe , RBC
production is still normal , Ferritin

- Circulating-Fe (SI) begin , Transf-

Receptor .

* Stage-3 (Fe-Deficiency Anemia)

- Stadium of Iron Deficiency Anemia

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 LOGO

Stage-1 Stage-2 Stage-3

(prelatent) (latent) (IDA)

Marrow (-) (-)

Ferritin <12ug/L <12ug/L
Transf-Sat N <16% <16%
sTrfR N
Retic Hb N
content
Hb N N <
MCV N N <
Symptoms fatigue fatigue pallor
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 LOGO

Symptoms Morphology SI - TIBC Ferritin

IDA Anemia Hypo SI -

Micro TIBC

A.C D Anemia Hypo SI - N/

Micro TIBC /
N

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Pendekatan Diagnostik Anemia Defisiensi Fe LOGO

1. Anamnesis pola menstruasi, kehamilan /

persalinan, tendensi perdarahan,
penyakit kronis, diet, pekerjaan,
riwayat bepergian

2. Pemeriksaan fisik sistematik dari seluruh

permukaan tubuh sampai ke organ dalam ( hati,
limpa, kelenjar getah bening (lymphnodes)

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 LOGO

3. Laboratorium- Hema (DL, LED, Hapusan

darah tepi, Retikulosit)
- Serum (SI,TIBC,Ferritin, Bilirubin)
- BMA (Bone Marrow Aspiration)
- Pemeriksaan Urine dan tinja

4. Penunjang - Radiology (EKG, USG)

- Endoscopy

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 LOGO
SI TIBC

Normal N N
(1/3 mol.Trsf)
IDA

An.of Chronic N/
Disease

Fe Overload N/

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Pemeriksaan Lab. Anemia def. Fe LOGO

1. CBC confirm Anemia & find hypochromic

microcytic picture from BSE and Red
Cells Indices ( Hb, PCV ,MCV , MCH ,
MCHC)

2. SI Fe2+ released from Transferrin + ferrozine

(chromagen) measured colored
complex
TIBC serum + excess FeCl2 to fill all Transferrin-
binding sites the excess Fe is fixed by Mg-
carbonate Fe-saturated Transferrin is
measured with Ferrozine (= TIBC)

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 LOGO

% Saturasi Transferrin = SI/TIBC X 100%

Erythropoeisis impaired when % Tf.Sat < 15%

3. Ferritin Serum :
Serum Ferritin level ~ Fe-storage
Ferritin <15 ug/L Definitive Fe-Deficient
N/ Ferritin in IDA , if :
- impaired liver function ( damaged
hepatocyte),
hemolysis, inflammation / infection /
malignancy ( Ferritin = acute-phase
protein )

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 LOGO

4. Transferrin Serum :
measured by immunodiffusion methode
Normal value : 2-4 g/L

5. Bone Marrows Aspirate evaluation :

( using Perls or Prussian Blue stain )

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Anemia of Chronic Infection LOGO

Gejala klinis miripdengan anemia def.Fe

Gambaran lab. hematologi = Anemia def. Fe
(An.Hypo-Micro, MCV, MCH, SI) , tapi
TIBC N/ and Ferritin N/)
Pathogenesis :
Fe storage // Transferrin

Tissues / RES

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Penyebab menurunnya circulating LOGO
Fe :

1. Impairment of Fe release from

macrophage in competing with
lactoferrin, phagocytes product , even
storage-Fe is still enough .

2. Inadequate EPO Respons towards

anemia (effects of cytokine production by
macrophage) .

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Diagnosis Anemia akibat penyakit kronis: LOGO

lab hematologi:
- Anemia hipokromik mikrositik
- SI , TIBC /N , Ferritin N/
( jika Ferritin , !An. Def.Fe )
- Inflamasi / infeksi (+) :
CRP and LED

Problem: IDA with inflammation ferritin
(falsely diagnosed as ACD) ; it can be
differentiated by sTfR exam (serum
transferrin receptor) that in IDA but normal
in ACD .

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Anemia Sideroblastik LOGO

Defek pada sintesis Heme akumulasi Fe di

mitochondria degenerasi Fe granula Fe
di sekitar inti normoblast, membentuk
struktur spt cincin {paling jelas terlihat
dengan pengecatan Perl (Perls stain) }
Ringed Sideroblast (karakteristik anemia
Sideroblastik)

Sideroblast bisa dijumpai secara normal di

sutul

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 LOGO

Sideroblast and Ringed Sideroblast ( in Sideroblastic Anemia )

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 LOGO

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 LOGO

Classification of Sideroblastic Anemia

1. Hereditary : X-linked, defect in heme-

synthesis enzyme pathway

Fe absorption % of Transferrin saturation

and Ferritin level

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 LOGO

2. Acquired :
- Primary :

Stem cell clonal mutations(MDS =
MyeloDysplastic Syndromes , RA-RS)
Normochromic-macrocytic anemia .
Marrow : erythroid hyperplasia with
dysplastic or megaloblastic appearance
- ringed sideroblast in normoblast .

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 LOGO
-
- Secondary;
Abnormal metabolism of Vit.B6 (alcoholism,
malabsorption) , impairment of heme
synthesis ( Pb intoxication) , Rhematoid
Arthritis , or An.megaloblastik .

Usually related to myeloproliferative diseases

( AML, Myelofibrosis, Polycythemia or
another types of MDS )

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Macrocytic Anemia LOGO

- Non-Megaloblastic Macrocytic Anemia :

Reticulocytosis
Liver disease / Alcoholism
Myelodysplastic Syndrome
Erythroleukemia (FAB-M6)

- Megaloblastic Macrocytic Anemia

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Megaloblastic Macrocytic Anemia LOGO

macrocyte = erythrocyte with MCV > normal .

macrocyte/microcyte depend on the balance between
nuclei & cytoplasmic maturation .

(nuclear dividing stopped when intracellular Hb

production reach a proper level ) .
If nuclear maturation delayed ( in DNA
synthesiss defect ) or cytoplasmic maturation
( increase of EPOs activities ) critical level of
Hb achieved earlier Macrocyte

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 LOGO

Megaloblast = bigger than normal normoblast

.
Megaloblastic changes = increased size of
hemopoietic precursor cells in bone marrow (
not only in normoblast !)

Primary defect : Defect of DNA synthesis

( altered almost all active cells / organs i.e :
hemopoietic tissue, epithelial cells , mucous
cells, etc )

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 LOGO

Etiology of DNA synthesis defect :

deficiency of vit.B12 and folic acid
maturation dysharmony between nuclei &
cytoplasm (delayed nuclei maturation)
increased cels (megaloblastic changes)
marrows ineffective erythropoiesis
intramedullary hemolysis total/indirect Bili
and LDH .

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 LOGO

Deficiency of Folic acid:

- Inadequate diet
(intake < / demand in pregnancy -
lactation , childs growth / malabsorption
in tropical sprue / bowel resection / small
intestine inflammation )

- Drugs effect (anti-epilepsi)
- FA loss (dialysis)

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 LOGO

Deficiency of Folic acid:

- Inadequate diet
(intake < / demand in pregnancy -
lactation , childs growth / malabsorption
in tropical sprue / bowel resection / small
intestine inflammation )

- Drugs effect (anti-epilepsi)
- FA loss (dialysis)

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 LOGO

Deficiency of Vit.B12:

- Inadequate diet :
Intake < in vegetarians , demand ,
impaired absorption caused by
decreased Intrinsic Factor
( gastrectomy , pernicious anemia )
Malabsorption (bowel infection , worms
/ blind loop syndr )

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VITAMIN B12 ASAM FOLAT
LOGO

-Food from animal products -Limited sources (vegetable ,

-Heat stabile
-Storage : enough for 3 yrs
-Relatively low needs (only
1% of folate requirements)
CAUSE OF DEFICIENCY
fruits)
-Heat labile
-Storage enough only for 3
mths
-Higher folate needs
CAUSE OF DEFICIENCY

-Vegetarian (seldom) -Nutrition (alcoholism, goats

-Impaired Intrinsic Factor milk diet)
(pernicious anemia) -Prematurity
-Gastrectomy -Hemodyalisis
-Atropic Gastritis -Bowel resection
-Anticonvulsant, alcoholism -Pregnancy
-Anticonvulsant , MTX
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Pathogenesis of Megaloblastic Anemia :LOGO

Megaloblastic changes
atrophy of tongue papilla & mucosal GI
glossitis , gastritis, nausea , constipation.
B12 defic demyelinisation of spinal cord &
peripheral nerve loss of foots balance /
sensory (Neuropatia)
FA defic hyperhomocysteinemia
thrombosis and vascular occlusion .

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B12 Metabolism LOGO

Vit.B12 purine & pyrimidin synthesis

synthesis DNA & RNA mitosis and
maturation
Vit.B12 made from microbiological source
because plants do not produce B12 ( meat ,
liver, eggs and milk are rich of Vit B12 ).
Vit.B12 content in the daily diet is 5-3ug ,
daily requirement of B12 is 1-3 ug, and B12
bodys storage is 2-5 mg (enough for 3 yrs)

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 LOGO
Vit.B12 absorption
B12 diet in gaster bind by IF (Intrinsic Factor)
produced by parietal cells IF-B12 complex ileum
: B12 absorbed , IF freed into the lumen

impaired IF : gastrectomy/gastritis/ Auto-Ab-antiIF or

Auto-Ab-antiparietal) no absorption of B12
impaired DNA synthesis (Pernicious Anemia with
Achlorhydria)

Pernicious Anemia = autoimmune disease auto-Ab

to parietal cells (Anti-IF or Anti-Parietal)

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Hematological pictures of Megaloblastic AnemiaLOGO

Bone Marrow :
- megaloblastosis
- ineffective erythropoiesis

Peripheral blood :
- Oval macrocytosis
- Hypersegmented neutrophil ( five 5-lobed
cells or one 6-lobed cell) or the mean lobes
of 100 neutrophils is > 3.4

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Megaloblastic Anemia LOGO

! find oval-Macrocyte cell and hypersegmenteneutrophil .

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Diagnosis of Megaloblastic Anemia LOGO

Screening :
- CBC , Neutrophils lobe count
- Serum Indirect Bilirubin , LDH (lactate
dehydrogenase)

Spesific tests :
- Bone Marrow Aspiration: megaloblastosis &
megaloblastic changes, erythropoietic activitiy ( ineffective
erythropoiesis)
- Folate & Vit.B12 assay
- Gastric juice analysis
- Schilling Tests
- Antibody Assay

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 Anemia Hemolitik LOGO

Anemia hemolitik: anemia yang disebabkan

oleh proses hemolitik.
Hemolisis: pemecahan eritrosit sebelum
waktunya (sebelum masa hidup rerata eritrosit,
yaitu 120 hari).
(Proses pemecahan eri karena sdh waktunya!
senescence=penuaan)
Hemolisis dapat terjadi di dalam pembuluh
darah (hemolisis intravaskular) dan di luar
pembuluh darah (hemolisis ekstravaskular).

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HEMOLYTIC ANEMIA LOGO

Normal red cells survival = 110-120 days

destructed by macrophage in marrow and
spleen .
When the survival are shortened EPO
production is stimulated (compensated)
no Hb changes anemia () .
If the destruction is acute or chronic with very
shortened life of red cells , there will no
compensation anemia (+) .

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Definition of Hemolytic Anemia : LOGO

anemia caused by shortened red cells

survival as a result of excessive
uncompensated destruction of red cells .

Hemolytic process = every process of red

cells destruction with still / without
compensated by bone marrow anemia is
not always present .

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- Compensation ability of bone marrow : LOGO

Ability to red cells production ( 6-8 x normal

) :
- survival shorten production 2x
- survival shorten production 4x
- survival shorten 1/6 production 6x
- survival shorten 1/8 production 8x

of production 6-8 x is maksimum .
If red cells live only 20 days anemia (+).

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 LOGO
Diagnostic approach in Hemolytic Anemia :
1. Confirm anemia (Hb/PCV/RBC)
an acute case usually acquired , and
chronic case is mostly hereditary .

2. To find the signs of hemolytic process .

3. Extra or Intravascular ?
4. Hereditary or acquired ?
5. The cause of hemolysis episodes .

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The signs of Hemolytic process : LOGO

1. Increased of red cells destruction

- Unconjug.bilirubin serum jaundice
- Urobilinogenuria
- Hb-uria sign of intravascular hemolysis
- Abdom.pain splenomegaly, spleen infarction
- Legs Ulcer intrinsic defect of erythrocyte
- Haptoglobin serum /neg intravascular
hemolisys .

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 LOGO

2.Destruksi eritrosit :
- Microspherocyte, Fragmentocyte, Poikilocyte
- Erythrocyte Osmotic Fragility
- Positive Autohemolysis test
- Shortened of red cells survival

3. Tanda Peningkatan Eritropoisis:

- Reticulocytosis
- Normoblastosis
- Erythropoietic Hyperplasia in bone marrow

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 LOGO

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 LOGO

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 LOGO

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 LOGO

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 Hemolisis Ekstra vaskular LOGO

Hemolisis ekstravaskular lebih sering dijumpai

dibandingkan hemolisis intravaskular
Hemolisis terjadi di sel makrofag dari sistem
retikuloendothelial (RES) terutama pada Lien, hepar
dan sutul karena sel ini mengandung enzim heme
oksigenase
Lisis terjadi karena kerusakan membran eritrosit
(misal Akibat reaksi Ag-Ab; presipitasi hb di
sitoplasma, menurunnya fleksibilitas eri,dll)
 LOGO

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 LOGO

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 LOGO

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 Klasifikasi Anemia Hemolitik LOGO

Dibagi atas 2 golongan besar, yaitu:

1. Anemia hemolitik karena faktor di dalam
eritrosit sendiri (gangguan intra korpuskuler)
2. Anemia hemolitik karena faktor di luar
eritrosit (gangguan ekstra korpuskular)

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 LOGO
lanjutan.Klasifikasi anemia hemolitik :

1. Gangguan intra korpuskular (Hereditary

Hemolytic Anemia )

- Membrane abnormality (hereditary
spherocytosis , hereditary ovalocytosis )
- defect of globin chain (Thalassemia, Hb-
pathia)
- enzyme defect ( G-6PD deficiency , PK-
deficiency)

87
Hereditary Spherocytosis :
LOGO

88
Hereditary Ovalocytosis : LOGO

89
Lanjutanklasifikasi anemia hemolitik
LOGO

2. Gangguan ekstrakorpuskular
(Acquired Hemolytic Anemia):

- physical / chemical substances

- infections (bacteria, parasites, viruses,
fungi)
- mechanical trauma (prostetic heart valves)
- Immune mechanism (Alloimmune /
Autoimmune / Drug-Induced HA)

90
- Hereditary Spherocytosis : LOGO

autosomal dominant
Spherocytosis, decreased membrane surface area
relative to cell volume osmotic fragility test (OFT)
among the family member .
The primary lesion is caused by membrane protein
defects (of spectrin) cytoskeleton instability .
60% - chronic anemia , jaundice, splenomegaly, 20%
without hemolysis / splenomegaly .
Bilirubin excretion ,causing bilestone in USG.

91
Thalassemia : LOGO

Defect of 1 or more globin-chain synthesis (the

amount = quantitatively) :

- deficiency of globin-chain -thalassemia

- deficiency of globin-chain -thalassemia
- deficiency of globin-chain -thalassemia

the primary defects in Hb-pathia is in the globin amino

acids structure (qualitatively)

92
 LOGO

93
 LOGO

94
-Thalassemia LOGO

-Thalassemia = is caused by the impairment

of -globin chain production/synthesis .

-globin chain synthesis is directed by 2

pairs of -gene (4 locus -gen) depending
of the number of defected locus 3 types of
-Thalassemia (-thal trait , HbH Disease, and
HbBarts Hydrops Fetalis)

95
Clinical consequences in -Thalassemia LOGO

Deficiency of -globin chain excess of ,

chain since fetal life to form 4-tetramers
(HbH) or 4-tetramers (HbBart) .

Defect of 1-2 -Gen = -trait (clinically good)

Defect of 3 -Gen = HbH disease ( Hb 10-11 g/

dl) excess of -chain to form 4-
tetramers (HbH) as intracellular inclusion
detected by BCB-stain .

96
HbH-inclusion (4) in HbH Disease as shown in BCB
staining (compare with reticulocyte) LOGO

97
 LOGO

Defect of 4 -gene (HbBartshydrops fetalis)

clinically severe , stillborn baby with
hydrops fetalis ( severe hypoxia ) .
HbBarts = 4-tetramers (excess of -chains
that unable to form HbF ) .

HbBarts and HbH inclusions precipitated in

red cells membrane mechanical trapping
in spleen macrophagic phagocytosis
hemolysis .

98
 LOGO

99
 LOGO

100
- -Thalassemia LOGO

Clinically consequences in -Thalassemia :

- No problems during fetal life because HbF
synthesis is normally produced
(normal and chains)

- When HbA is dominantly needed , the
clinically
problems exist as incapability to synthesize
HbA (22) excess of -chain
compensated of and production
HbA2
(in -Thalassemia minor) and HbF (in
-Thalassemia mayor)

101
 -Thalassemia mayor : LOGO

- severe anemia repeated transfusion is

oftenly needed Fe hemochromatosis

- chronic ineffective erythropoiesis

medullary hypertrophy in childhood facial
malformation:
* Frontal bossing
* Maxillary hypertrophy
* Hypertelorism (mongoloids eye)

102
- -chain deletion forms : LOGO

0-Thalassemia : no -chain
production.
+Thalassemia : -chain production
<<
in heterozygous case : medium severe
in homozygous : severe (Cooleys
anemia)

103
 LOGO

104
Laboratory Diagnosis in Thalassemia LOGO

1. CBC, Peripheral Blood Smear

2. Hb-Electrophoresis : in Celulose-Acetat (pH

8.4) for thalassemia and Hb-pathia
screening
Using hemolysate formed bands of
different types of Hb ( normal : bands A, F,
and A2 , measured densitometrically)

105
 LOGO

106
 Lanjutan..Lab diagnosis in thalasemia LOGO

3. HbA2 mesurement to diagnose -Thalassemia trait

using anion-exchange resin column chromatography

in both HbELP and chromatography , HbC, HbE and

HbO can interrupt the conclusion because of the
same band location with HbA2 .

4. HbF determination :
- Alkali Denaturation Test
- Acid-elution (Kleihauer) test
- RID or ELISA methods

107
 LOGO

5. HbH Inclusion detection :

- Supravital staining using Brilliant
Cresyl Blue (BCB) or NewMethylene
Blue (NMB)
- HbH inclusion seen as dispersed blue-
green granules in red cells
(compare with reticulocyte as a filament)
- in HbH disease : HbH inclusion +++
- in Thalassemia--trait : HbH inclusion +
in 1: 10000 eritrosit .

108
 Defisiensi G-6PD LOGO

- Oxidant produce H2O2 oxidizing

Hbs free sulfhydryl to form Sulf-Hb
aggregates that precipitated as Heinz
Bodies destructed in spleen .

- Oxidant / Sulf-Hb are controlled by
Reduced Glutathione (GSH)

109
 LOGO

110
 LOGO

- X-linked, 300 variants .

normal G-6PD genes : - type B (GdB)
- type A (GdA)
- Abnormal enzyme types :
1. GdA (type A)
2. Gd-Mediterranean (GdMed)
3. Gd-Canton : many in Asia

- G-6PD deficient red cells are resistent

to Plasmodium Falciparum .

111
 LOGO

- Substances causing lysis in G-6PD

deficiency :

1. Antimalaria 6. Fava beans

2. Sulfonamides 7. Naphtalene
3. Vit.K, Vit.C 8. Uremia
4. Lung Infection 9. Antibiotics
(virus,bacteria) (Penicilline ,
5. Antipyreticum streptomycine

112
 LOGO

The highest G-6PD activity is in

reticulocyte .
G-6PD screening test :

Tests principle :
G-6PD
G-6P + NADP 6-PG + NADPH
UV

(fluorescence)

113
 LOGO
Acquired Hemolytic Anemia :

- Secondary Hemolytic Anemia caused by

infection / systemic disorders :

Malignancy Autoimmune-reacted hemolysis

, microangiopathy or hypersplenisme ,
appearing Anemia of chronic disease,
bleeding tendencies, and marrows
suppression

114
 LOGO

Disseminated Intravascular Coagulation

(DIC):
Systemic intravascular coagulation fibrin
deposit intravascularly / endothelial damage
(microangiopathyi) caused by sepsis red
cells destruction .

Chronic Liver Disease : hemolysis caused by

hypersplenism .

Chronic Renal Disease: hemolysis caused by

microangiopathy

115
Acquired Hemolytic Anemia (extracorpusc.) LOGO

Immune Hemolytic Anemia

Red cell membrane-bound Ab hemolysis .
The speed & hemolysis location depend on
IgG or IgM, and the ability to activate
complement .
Optimal temperature to bind Ab :
370C Warm-IgG-Type
<300C Cold-IgG-Type

116
 Lanjutan.acquired hemolytic anemia LOGO

Cell+IgG destructed by spleen

Cell+IgM enhance the activation of
complements cascade intravascular
hemolysis

Immune destruction often cause minimally

membrane damage shape change into
spherocyte .

117
 LOGO

Immune Hemolytic Anemia classification :

1. Alloimmune : Transfusion Rx , Hemolytic
Disease of the Newborn (HDN)

2. Autoimmune : Warm/Cold AIHA,
Paroxysmal Cold Hb-uria (PCH)

3. Drug-induced HA : penicilline type,
aldomet, and stibophen type .

118
Hemolytic Disease of the Newborn (HDN) LOGO
Rh-neg mother , with Rh-Pos fetus , during I and second pregnancy

119
Antiglobulin Tests (Coombs) : LOGO

Direct Coombs Test (Direct Antiglobulin Test/

DAT) = Ab detection test (IgG and or C3d /
complement-bound red cells) .

Indirect Coombs Test = test for serum free
Ab .

DAT usually positive in AIHA (.

120
Drug-Induced hemolytic anemia : LOGO

Penicilline type : drug as hapten binds red cell

membrane antigenic stimulate Ab production
against Drug in drug-red cell complex

Phenacetin/Quinidin type : Drug (hapten) adsorbed

protein stimulated-Ab binds drug-protein complex
activate complement red cell lysis.

Aldomet type : drug change red cell membranes

structure detected as foreign cell Autoantibody
production .

121
 LOGO

122
Aplastic (Hypoplastic?) Anemia LOGO

Severe & fatal Anemia because of red cells/

leucocytes/platelet production (pancytopenia)
caused by Stem Cells impairment (radiation,
chemicals, drugs, or genetic matters)

Marrow aplasia / hypoplasia-causing

substances - radiation , benzene,
cytostatics (6-MP,
busulfan), arsen, chloramphenicol,
anticonvulsant (phenytoin), analgetic
(phenylbutazone) , DDT, etc

123
 LOGO
Symptoms & Lab.appearance of Aplastic Anemia

fatigue, palpitation, infections, bleeding tendency

Lab : - pancytopenia
- normochromic normocytic
- dry-tap marrow , hypocellularity

Prognosis :
- bad especially for < 40 yrs old patients
marrow transplantation .

124
- Treatment for Aplastic Anemia : LOGO

1. Avoid every toxic material

2. Avoid infections / bleeding tendency
3. Use Washed-Erythrocyte if transfusion is
needed or Plat.Concentrate (PC) for any
profuse bleeding ( give corticosteroid if
bleeding is minimal)
4. Marrow stimulants (androgenic hormon )
5. Marrow Transplantation

125
POLISITEMIA
(ERITROSITOSIS) LOGO

Peningkatan patologis massa eritrosit

massa eritrosit normal : (sea level)
- o : 26 - 32 ml / kg BB
- o : 23 - 29 ml / kg BB
eritrositosis : massa eritrosit > normal
( PCV : o >51% ; o >48% )
 LOGO

Klasifikasi :
I. Primer (Otonomik)
A. Polisitemia Vera
B. Eritrositosis Murni (Eritremia)
II. Sekunder
A. Fisiologis (Oksigenasi Jaringan )
B. Non-fisiologis (Oksigenasi Jaringan N)
III. Eritrositosis Relatif
 ERYTHROCYTOSIS - DIAGNOSTIC TESTS LOGO

Complete Blood Count

Bone Marrow examination
Arterial Blood Gas analysis
Leukocyte Alkaline Phosphatase
P5O
IVP or renal ultrasound
Liver ultrasound or CT scan
Erythropoietin level
Erythroid progenitor assay
Sleep apnea evaluation
 LOGO
POLISITEMIA VERA
Proliferasi klonal neoplastik sel
progenitor hematopoitik pluripoten
Kriteria diagnosis P.V. :

Kategori A
1.Massa eritrosit:
Lk > 36 ml / kgBB (PCV > 54%)
Pr > 32 ml / kg BB (PCV > 51%)
2. Saturasi oksigen > 92%
3. Splenomegali
 LOGO

Kategori B
1. Trombositosis (> 400.000 / l)
2. Lekositosis (> 12.000 / l)
3. Skor LAP
4. B12 serum > 900 pg/ml

Diagnosis PV +bila :
A1 ++A2 ++ A3 + atau
A1 ++A2 ++ dan 2 dari kategori B +
 LOGO
PRIMARY PURE ERYTHROCYTOSIS
( ERYTHREMIA )

peningkatan massa eritrosit murni

tidak ada penyebab eritrositosis sekunder
kadar eritropoitin normal atau rendah
mungkin akibat mutasi gene reseptor
eritropoitin progenitor eritroid jadi lebih
sensitif terhadap eritropoitin.
 LOGO
II. ERITROSITOSIS SEKUNDER

Merupakan respons terhadap keadaan lain

yang bersifat :
- fisiologis : akibat oksigenasi jaringan yang
- non fisiologis : tanpa penurunan oksigenasi
jaringan
 LOGO
III. ERITROSITOSIS RELATIF

Sindroma Gaisbock
Stress erythrocytosis
Pseudo erythrocytosis

- Massa eritrosit tinggi normal

- Volume plasma rendah
LOGO

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 SOAL LATIHAN : LOGO

1. Nyonya Ana, usia 40 tahun, MRS (Masuk Rumah Sakit)

dengan keluhan pusing, dan badan terasa lemah. Pemeriksaan fisik:
KU lemah, Tensi: 100/60 mmHg, Nadi:90 x/menit, RR: 20 x/menit,
suhu:37C. Kepala/Leher: anemia (+), tidak dijumpai ikterus,
dyspnea dan sianosis, Thorak/Cor dan Abdomen :dalam batas
normal (dbn). Extremitas: dbn. Hasil laboratorium: Hb 8 g/dl, RBC
3,20 x 1012/L, Hematokrit 24 %, MCV 75 fl, MCH 25 pg, MCHC
33 g/dl. Jika anda adalah dokter jaga di RS tersebut, dari data yang
ada, kemungkinan diagnosis pasien tersebut adalah:

A. Anemia normokromik-normositik
B. Anemia hipokromik-mikrositik
C. Anemia makrositik
D. Anemia makrositik-megaloblastik
E. Anemia makrositik-non megaloblastik

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 Lanjutan ...soal latihan LOGO

2. Dari kasus ny. Ana, 40 tahun tersebut, diagnosis diferensial untuk

penyebab anemianya adalah:

A. Anemia defisiensi folat, anemia defisiensi Vitamin B12,

B. Anemia karena perdarahan akut, anemia aplastik
C. Anemia defisiensi besi, thalasemia, anemia sideroblastik
D. Anemia hemolitik, anemia pada penyakit mielofibrosis
E. Anemia pada penyakit liver, anemia pada penyakit hipotiroid

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 Lanjutan ...soal latihan LOGO

3. Dari soal kasus Ny. Ana, 40 tahun tersebut, langkah

pemeriksaan laboratorium selanjutnya yang perlu
dilakukan untuk konfirmasi diagnosis adalah:

A. pemeriksaan bilirubin, haptoglobin, hitung retikulosit

B. Serum Iron, TIBC dan Feritin
C. Pemeriksaan B12 dan asam folat dalam darah
D. Pemeriksaan T3, T4 dan TSH
E. Pemeriksaan Aspirasi sumsum tulang

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 CLINICAL CASE LOGO

A 35-year-old man complains of chronic physical fatigue, which

began 3-4 weeks ago. He said he felt tired all of the time even
through his occupation as a software developer was mentally but
not physically demanding. He breathed comfortably at rest but,
when he exerted himself, he experienced difficulty in breathing and
had hard time catching his breath. He also complained of more
than usual mental fatigue, confessing an increasing inability to
concentrate and focus his attention on tasks at hands. Colleagues
noticed his pallor and his inattentiveness at brainstorming sessions
and suggested he reschedule his annual physical examination for
an earlier date. He complained of vague abdominal pain and sense
of abdominal fullness. His appetite was depressed, and he thought
perhaps his physical and mental symptoms were caused by poor
diet. However, attempts to increase eating resulted in nausea. His
stools, he said, were sometimes loose and tarry. Eventually,
increased heart palpitations and chest pain made him seek medical
advice
 LOGO
Laboratory findings revealed the following:
Laboratory test Patient Normal
RBC (red blood cell count) 3.5 T/L 4.5-6.0 T/L
HCT (hematocrit ratio) 28% 40-52%
Hb (hemoglobin) 8.0g/dL 13-17g/dL
MCV (mean corpuscular 70fL 78-95fL
volume)
MCH (mean corpuscular 22.8pg 29pg
hemoglobin)
MCHC (mean corpuscular 28% 34%
hemoglobin concentration)
 QUESTIONS LOGO

Case history questions:

1. What general medical condition is suggested by
the persons symptoms?
2. What fundamental change in function of blood
related to the red blood cells could
simultaneously affect the function of several
systems (cardiovascular, respiratory,
gastrointestinal, and others)?
3. What specific diagnosis is supported by the
laboratory findings?
4. How could the stool be related to the laboratory
findings?
 ANSWER LOGO

1. Answers:
Anemia
2. A reduction in oxygen-carrying capacity of the
blood and thus a reduction in the delivery of
oxygen to various body tissues
3. An iron defficiency anemia
4. Most cases of iron-defficiency anemia result
from internal blood loss.
Dark, tarry loose stools suggest bleeding from
the gastrointestinal tract and warrant further
tests to determine the exact cause
LOGO

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