Gangguan Eritrosit

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 Gangguan Eritrosit

Anemia

Polisitemia

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 ANEMIA
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

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

• Hb ↓
• PCV ↓ Hypoxia → Otak , Otot
• RBC ↓
Kompensasi :
- Hear t 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 ↑ .
5
 Klasifikasi Anemia

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
E. Gangguan karena mekanisme lain:
 Anemia karena penyakit kronis,
 anemia sideroblastik
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 Anemia karena infiltrasi sumsum tulang
 Lanjutan…..anemia berdasarkan patofisiologi

II. Peningkatan destruksi sel darah merah:

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

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 Anemia
Anemia berdasarkan morfologi
Anemia sec. morfologi eritrosit, dilihat dari:
 ukuran dan warna di bawah mikroskop atau
 indeks eritrosit (MCV, MCH, dan MCHC)
(dihitung berdasarkan Hb, Ht & jlh eri)
- Kriteria Ukuran (size): Normositik, Mikrositik,
Makrositik
- Kriteria Warna (pucat): Normokromik, Hipokromik

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9
 Klasifikasi Anemia secara morfologi

1. Anemia Hipokromik-Mikrositik.

2. Anemia Normokromik-Normositik

3. Anemia Makrositik

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 Anemia Anemia Anemia makrositik
hipokromik- normokromik-
mikrositik normositik

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

MCV <80 fl; MCV 80 -95 fl

MCV > 95 fl
MCH <27 pg MCH 27-34 pg

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 Pendekatan diagnostik Anemia:
• 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)

12
• Pemeriksaan Laboratorium

- CBC (complete blood count )→ to confirm

anemia (Hb, PCV, RBC) & the type of anemia
(MCV; MCH; MCHC), RDW
- Hitung retikulosit → menggambarkan respons
sum2 tulang .
- MDT : 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) . 13
Lanjutan…. Pendekatan Doagnostik…
- 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

14
15
16
Anemia Hipokromik-Mikrositik

- 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

17
18
 ANEMIA DEFISIENSI BESI
• 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
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dengan preparat Fe
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Faktor Penyebab (Etiologi)

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)
21
Lanjutan….Faktor Penyebab

II. Inadequate presentation to erythroid

precursors:
- atransferrinemia
- Anti TrfR Ab

III. Abnormal Fe balance :

- Aceruloplasminemia
- Autosomal dominant hemochromatosis
( mutations in ferroportin )

22
 Patogenesis desifisiensi Fe
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 cell’s
membrane → RBC deformability ↓ → RBC viability ↓→
RBC destruction ↑ especially in spleen → reduced RBC
survival
23
 Status besi tubuh:
• 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 dan Sum2 tulang→
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)

24
• 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)

25
 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
26
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

27
• 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.

28
Siklus Fe dalam tubuh :

Diet’s Iron → duodenum / proximal jejunum .

Iron from gut → released into circulation , bound

to transferin → distributed to body’s organ /
tissues( to bone marrow as a part of heme / Hb )
→ circulate inside red blood cells with blood flow

29
The development of IDA

• Stage-1 (prelatent Fe-deficient):

- progressive loss of storage-Fe

- body’s 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

30
 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

31
 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

32
 Symptoms Morphology SI - TIBC Ferritin

IDA Hypo – SI↓ - ↓↓

Anemia Micro TIBC ↑

A.C D Hypo – SI ↓ -
Anemia N/ ↑
Micro TIBC ↓/N

33
 Pendekatan Diagnostik Anemia
Defisiensi Fe
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)

34
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

35
 SI TIBC

Normal N
(1/3 mol.Trsf)

IDA ↓ ↑

An.of Chronic
Disease
↓ N/↓

Fe Overload ↑↑ N/↑

36
 Pemeriksaan Lab. Anemia def. Fe

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)

37
 % 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 )

38
4. Transferrin Serum :
measured by immunodiffusion methode
Normal value : 2-4 g/L

5. Bone Marrow’s Aspirate evaluation :

( using Perls or Prussian Blue stain )

39
 Anemia of Chronic Infection

• 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

40
Penyebab menurunnya ‘circulating
Fe’ :

1. Impairment of Fe release from

macrophage in competing with
lactoferrin, phagocyte’s product , even
storage-Fe is still enough .

2. Inadequate EPO Respons towards

anemia (effects of cytokine production by
macrophage) .

41
Diagnosis Anemia akibat penyakit kronis:
• 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 .
42
 Anemia Sideroblastik
• 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
sum2 tulang.
43
Sideroblast and Ringed Sideroblast ( in
Sideroblastic Anemia )

44
45
• Classification of Sideroblastic Anemia

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

enzyme pathway

Fe absorption ↑ → % of Transferrin saturation

and Ferritin level ↑

46
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 .
47
- 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 )

48
 Macrocytic Anemia

- Non-Megaloblastic Macrocytic Anemia :

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

- Megaloblastic Macrocytic Anemia

49
Megaloblastic Macrocytic Anemia
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 synthesis’s
defect ) or cytoplasmic maturation ↑ ( increase of
EPO’s activities ) → critical level of Hb achieved
earlier → Macrocyte

50
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 )
51
• Etiology of DNA synthesis defect :

Deficiency of vit.B12 and folic acid →

maturation dysharmony between nuclei &
cytoplasm (delayed nuclei maturation) →
increased cels (megaloblastic changes) →
marrow’s ineffective erythropoiesis →
intramedullary hemolysis → total/indirect Bili
and LDH ↑.

52
• Deficiency of Folic acid:

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

- Drug’s effect (anti-epilepsi)

- FA loss ↑ (dialysis) 53
• Deficiency of Folic acid:

- Inadequate diet
(intake < / demand ↑ in pregnancy -
lactation , child’s growth / malabsorption

in tropical sprue / bowel resection / small

intestine inflammation )

- Drug’s effect (anti-epilepsi)

- FA loss ↑ (dialysis)
54
• 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 )

55
VITAMIN B12 ASAM FOLAT
-Food from animal products -Limited sources (vegetable ,
-Heat stabile
-Storage : enough for 3 yrs fruits)
-Relatively low needs (only -Heat labile
1% of folate requirements) -Storage enough only for 3
mths
-Higher folate needs
CAUSE OF DEFICIENCY CAUSE OF DEFICIENCY
-Vegetarian (seldom) -Nutrition (alcoholism, goat’s
-Impaired Intrinsic Factor milk diet)
(pernicious anemia) -Prematurity
-Gastrectomy -Hemodyalisis
-Atropic Gastritis -Bowel resection
-Anticonvulsant, alcoholism -Pregnancy
-Anticonvulsant , MTX

56
Pathogenesis of Megaloblastic Anemia :

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

57
B12 Metabolism

• 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 body’s
storage is 2-5 mg (enough for 3 yrs)
58
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)

59
 Hematological pictures of Megaloblastic Anemia

• 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

60
Megaloblastic Anemia
 find oval-Macrocyte cell and hypersegmenteneutrophil .

61
 Diagnosis of Megaloblastic Anemia

• Screening :
- CBC , Neutrophil’s 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
62
 Anemia Hemolitik
• Anemia hemolitik: anemia yang disebabkan
oleh proses hemolitik.
• Hemolisis: pemecahan eritrosit sebelum
waktunya (sebelum masa hidup rerata
eritrosit, yaitu 120 hari).
(Proses pemecahan eritrosit 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

• Normal red cell’s 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 (+) .

64
Definition of Hemolytic Anemia :

• Anemia caused by shortened red cell’s

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 .

65
- Compensation ability of bone marrow :

• Ability to ↑ red cells production ( 6-8 x

normal ) :
- survival shorten ½ → production ↑ 2x
- survival shorten ¼ → 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 (+).

66
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 .
67
The signs of Hemolytic process :

1. Increased of red cells destruction

- Unconjug.bilirubin serum ↑ → jaundice
- Urobilinogenuria
- Hb-uria → sign of intravascular hemolysis
- Abdominal pain → splenomegaly, spleen
infarction
- Leg’s Ulcer → intrinsic defect of erythrocyte
- Haptoglobin serum ↓↓/neg → intravascular
hemolisys .

68
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

69
70
71
72
73
Hemolisis Ekstra vaskular
• Hemolisis ekstravaskular lebih sering dijumpai
dibandingkan hemolisis intravaskular
• Hemolisis terjadi di sel makrofag dari sistem
retikuloendothelial (RES) terutama pada Lien,
hepar dan sum2 tulang 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)
75
76
77
 Klasifikasi Anemia Hemolitik

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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 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)

79
Hereditary Spherocytosis :

80
Hereditary Ovalocytosis :

81
Lanjutan……klasifikasi anemia hemolitik
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)

82
- Hereditary Spherocytosis :
• 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.
83
Thalassemia :
• Defect of 1 or more globin-chain synthesis (the
amount = quantitatively) :

- Deficiency of α globin-chain → α-thalassemia.

- Deficiency of β globin-chain → β-thalassemia.
- Deficiency of δβ globin-chain → δβ-thalassemia

the primary defects in Hb-pathia is in the globin

amino acids structure (qualitatively)

84
85
86
α-Thalassemia

• α-Thalassemia = is caused by the impairment of

α-globin chain production/synthesis .

• α-globin chain synthesis is directed by 2 pairs of

α-gene (4 locus α-gen) → depending of the
number of defected locus → 3 types of α-
Thalassemia (α-thal trait , HbH Disease, and
HbBart’s Hydrops Fetalis)

87
HbH-inclusion (β4) in HbH Disease as shown in
BCB staining (compare with reticulocyte)

88
 Defisiensi G-6PD

- Oxidant → produce H2O2 → oxidizing

Hb’s free sulfhydryl → to form Sulf-Hb →

aggregates that precipitated as Heinz

Bodies → destructed in spleen.
- Oxidant / Sulf-Hb are controlled by
Reduced Glutathione (GSH)

89
90
- 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

91
• The highest G-6PD activity is in
reticulocyte .
• G-6PD screening test :

Test’s principle :
G-6PD
G-6P + NADP 6-PG + NADPH
UV
(fluorescence)

92
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 marrow’s suppression

93
• 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
94
Acquired Hemolytic Anemia (extracorpusc.)

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

95
 Lanjutan….acquired hemolytic anemia

• Cell+IgG → destructed by spleen

Cell+IgM → enhance the activation of
complement’s cascade → intravascular
hemolysis

• Immune destruction often cause minimally

membrane damage → shape change into
spherocyte .
96
• 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 .

97
Hemolytic Disease of the Newborn (HDN) –
Rh-neg mother , with Rh-Pos fetus, during I and
second pregnancy

98
Antiglobulin Tests (Coombs) :

• 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 (.

99
 Drug-Induced hemolytic anemia :
• 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 membrane’s

structure → detected as foreign cell →
Autoantibody production .
100
101
 Aplastic (Hypoplastic?) Anemia

• 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
102
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 .
103
- Treatment for Aplastic Anemia :

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

104
 POLISITEMIA
(ERITROSITOSIS)
• 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% )
• 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

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

• Diagnosis PV bila :
+
A1 ++A2 ++A3 + atau
A1 ++A2 ++dan 2 dari kategori B +
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.
 II. ERITROSITOSIS SEKUNDER

• Merupakan respons terhadap keadaan lain

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

• Sindroma Gaisbock
• Stress erythrocytosis
• Pseudo erythrocytosis

- Massa eritrosit tinggi normal

- Volume plasma rendah
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