Anemia hemolitik

dr Putra Hendra SpPD

UNIBA
Proses hemopoiesis
 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

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 Lanjutan..anemia berdasarkan patofisiologi

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 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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 Anemia

Acute Chronic
( < 7 Days ) ( > 2 Months )
 Acute anemia

Acute blood loss Acute hemolysis

History of History of

GI bleeding dark urine

hypermenorrhea jaundice
 Acute anemia

Acute blood loss Acute hemolysis

Intravascular Extravascular

- - Hb H with crisis
- Mis-match - HS with crisis
- AIHA
 Chronic anemia
Chronic
blood loss
RBC production Hemolysis

BM failure Precursors IVH EVH

Dietary intake
Bleeding
AA Iron def. Hx of
PNH Family history
Thalassemia
CRF
Absorption MAHA
tendency
Myeloph. dark urine Hx
HSof blood
Megaloblastic
Chronic blood transfusion
loss
 Anemia Hemolitik
Anemia karena peningkatan destruksi
eritrosit
Terjadi hiperplasi eritropoetik &
perluasan anatomis tulang
SS tl : 6 8 x N
Retikulosit meninggi
Proses hemolitik tidak selalu anemi
 - Compensation ability of bone marrow :

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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Hemoglobin (Hb)

www.drsarma.in
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Figure 19.5 Red Blood Cell
Turnover

Figure 19.5
16
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 Laboratory Evaluation of Hemolysis
Extravascular Intravascular
HEMATOLOGIC
Routine blood film Polychromatophilia Polychromatophilia
Reticulocyte count
Bone marrow Erythroid Erythroid
examination hyperplasia hyperplasia

PLASMA OR SERUM
Bilirubin Unconjugated Unconjugated
Haptoglobin , Absent Absent
Plasma hemoglobin N/
Lactate dehydrogenase (Variable) (Variable)

URINE
Bilirubin 0 0
Hemosiderin 0 +
Hemoglobin 0 + severe cases
Hemolytic Anemias
The signs of Hemolytic process

1. Increased of red cells destruction

- Unconjug.bilirubin serum jaundice
- Bilirubin conjugated
- Urobilinogen urine (++)
- Bilirubin urine
- splenomegaly spleen infarction abd pain
- Legs Ulcer intrinsic defect of erythrocyte
- Haptoglobin serum /neg intravascular
hemolisys .
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 Pembagian Anemia Hemolitik
1. Anemia hemolitik herediter (genetik)/intrinsik:
a. Defek membran: sperositosis,eliptosit, Spur cell
b. Defek enzim/metabolik : G6PD, Pyruvat kinase
c. Defek Hb (hemoglobinopati): sickle sel, HbC, HbD,
HbE,HbSC,HbM, Hb Koln&Zurich, Thalasemia

2. Anemia hemolitik akuisita/ekstrinsik:

a. Autoimun : AIHA
b. Isoimun : Rx Tranfusi
c. Hypersplenism
d. Mechanical trauma: MAHA
e. Lain2 : Obat zat kimia, mekanik, infeksi
 2.Kelainan eritrosit destruksi
- Microspherocyte, Fragmentocyte,
Poikilocyte
- Erythrocyte Osmotic Fragility
- Positive Autohemolysis test
- Shortened of red cells survival

3. Tanda Peningkatan Eritropoisis:

- Reticulocytosis
- Normoblastosis
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- Erythropoietic Hyperplasia in bone marrow

 Gambaran laboratorium
Anemia Hemolitik
1. Peningkatan destruksi eritrosit: bilirubin ,
urobilinogen urin , sterkobilinogen ,
haptoglobin serum
2. Peningkatan produksi eritrosit: retikulositosis,
normoblastosis , BM hiperplasi
3. Sdm rusak : Morfologi (fragmentosit, sferosit,
mikrosit), fragilitas osmotic abn,
Autohemolitik, Umur SDM memendek.
4. OFT : abnormal
5. Usia eritrosit memendek
Evaluation of Hemolysis
LDH: increases
Indirect bilirubin increases
(increased Hgb catabolism)
Haptoglobin decreases
Reticulocyte count increases
Urine hemosiderin test =
present for intravascular,
absent for extravascular
hemolysis!
Coombs test + = autoimmune
hemolytic anemia, - consider
PNH (abnormal GPI protein,
send flow for CD55 and CD59)
 Reticulocyte Count
Anemia with high retic # = appropriate response
Anemia with normal to low retic # = reduced marrow
response
Must adjust for anemia, use reticulocyte production index
Retic % x HCT/45 or x , nml is 1.0, less = inadeq. Retic
Or RI = retics x (Hct/45) / Correction Factor
CF: Hct 41-50 (1), 30-40 (1.5), 20-29 (2), 10-19 (2.5)
Reflects increased circulating time for retics as Epo pushes them out
of the marrow earlier
Red Cell Membrane Defects
 1. Sferositosis herediter
Autosomal dominan
Cacad struktur membran: Deficiency of Beta
Spectrin or AnkyrinSel menjadi sferis, mati
lebih dini
Mikrosferosit
Direk coomb test negatif
Autohemolitik
destruksi limpa >>
Pathophysiology of sickle cell disease
 Sickle cell disease
Normal adult spleen is
11cm in craniocaudal Auto-splenectomy
length.

This picture illustrates a

spleen that has infarcted
due to sickle cell disease
and shrunk to 4.5cm in
length. This spleen
would not be functional.
 Px:
Testwill confirm Hemolysis
P Smear: Spherocytes
Osmotic Fragility: Increased

Screen Family members

RBC Membrane
Osmotic Fragility
 Sickle Cell Anemia (HbSS)
1. 6 glu to val
2. tactoids at low oxygen tension
3. sickled red cells
4. small blood vessel occlusion
5. tissue infarction
Sickle Cell Anemia blood film

Sickle
Cells

Erythroblasts
Howell-
Jolly Body
Sickle Cell
Anemia

EM of red
cell showing
tactoids
Sickle Cell Anemia - treatment
Opiates and hydration for painful crises
Pneumococcal vaccination
Retinal surveillance
Hydroxyurea
Transfusion for serious manifestations
Stem cell transplant
Support, folate, iron chelation
 Sickle Cell Trait

Heterozygous state for HbS (HbAS)

No serious clinical consequences
Sudden death during intensive training
Hematuria, isosthenuria (renal papillary
necrosis)
Hemolytic Anemia: Intrinsic causes
Spherocytosis, Sickle Cell
42
Hereditary Spherocytosis :

43
Hereditary Ovalocytosis :

44
 Sickled red blood cells

Sickle Cell Disease (SCD)

2.Hereditary Elliptocytosis
Equatorial Africa, SE Asia
Functional abnormality in one or more anchor
proteins in RBC membrane- Alpha spectrin ,
Protein 4.1
Usually asymptomatic
Mx: Similar to H. spherocytosis
Variant:
3.SE-Asian ovalocytosis:
Common in Malaysia , Indonesia
Asymptomatic-usually
Cells oval , rigid ,resist invasion by malarial
parasites
Defek enzim
 G-6-PD deficiency

complication
 Defek enzim G6 PD
Sex linked
hemolysis when certain drugs are ingested
that induce oxidant stress on RBCs.
10% worlds population
Protection against Malaria
Faktor pencetus : infeksi, peny akut, obat2,
kacang fava
 Obat yang harus dihindari: Elitec
Methylene blue, Pyridium, Sulfacetamide,
Sulfasalazine, Isobutyl nitrite,
Nitrofuratoin, Primaquine,
Sulfamethoxazole (Bactrim), Toluidine
blue
 Management:
FolicAcid 5mg weekly, prophylaxis life long
Spleenectomy
Blood transfusion in , severe hemolytic crisis
 Diagnosis G6PD deficiency
evidence of hemolysis
Elevated bilirubin levels
Elevated serum LDH
Low serum haptoglobin
Hemoglobinuria
Elevated retic count
Low RBC count and hemoglobin
Methylene blue test
Methemoglobin reduction test

sel krenasi, fragmen, bite sel, blister sel, Heinz

bodies(Hb denaturasi/oksidasi)
Test : enzim G6 PD
Defek enzim Piruvat Kinase
Resesif autosomal homozigot
Sdm kaku krn pembentukan ATP
berkurang,
poikilositosis dg sdm distorsi
Prickle cells
Roulleaux >>
Autohemolisis
Test PK enzim
Anemia post splenektomia
What the hell is a Howell-Jolly
Body?
Mikroangioplastik hemolitik
anemia
Helmet sel
Teardrop Cells
 Hemoglobinopathies
Defined as a genetic defect that
results in an abnormal structure
of one or both of the globin
chains of the hemoglobin
molecule
62
Hemoglobins in normal adults

HbA HbF HbA2

98% ~1% <3.5%

 Defek Hb
Gangguan sintesa hemoglobin:
a. sel sabit
b. HbC
c. Hb SC, Hb D&E, Hb M
Ggn sintesa rantai globin: thalasemia
 Thalassemia Syndromes
Definition: inherited genetic disorders that cause
decreased production of normal Hgb A.
Three types:
Beta Thalassemia major
Beta Thalassemia minor
Alpha Thalassemia
 The Thalassemias

Syndromes in which the rate of synthesis of a

globin chain is reduced
beta thalassemia - reduced beta chain
synthesis
alpha thalassemia reduced alpha
chain synthesis
 Thalasemia
Thalasemia mayor= Cooley
Anemia mikrositik hipokromik berat
Signs and symptoms usually present in infants prior to
6 months of age including irritability, poor feeding,
pallor, growth retardation Growth failure and death
gangguan globin rantai beta, menimbulkan hemolisis
Iron overload
Hati&Limpa >>,
hiperplasi ss tl
elektroforesis HbF
 Tata laksana
life long chronic blood transfusions to
replace abnormal Hgb with normal Hgb.
Chronic transfusions lead to iron overload
which must be removed from the body
with chelation therapy (Desferol, Exjade)
to avoid liver and heart failure.
 Thalassemia Minor
Definition: less severe form of thalassemia whereby pt
does produce some normal Hgb A
Labs: Hgb electropheresis shows decreased Hgb A and
increased Hgb A2 and F. Peripheral smear often shows
target cells and basophilic stippling. Iron studies are
normal
Signs and Symptoms are usually absent
Physical exam: normal or may have splenomegaly
Management: no specific therapy is required. Iron
supplements are not recommended unless iron studies
confirm iron deficiency with low ferritin
 Thalasemia alfa
Rantai alfa penting utk HbF
Kehilangan 4 gen alfa kematian intra
uterin
Kehilangan 3 gen alfa anemia hemolitik
berat: mikrositik hipokromik dg
Splenomegali
Management: most often there is no
specific therapy. Genetic counseling
recommended for families with history of
thalassemias prior to pregnancy
RBC Target Cells
Anemia sel sabit : sel sabit dan
target sel
Target sel, tear drop sel eliptosit,
sperosit, mikrosit
Beta thalassemia major
Male 18 years
Mongoloid facies

Thalassemia
 Secondary
AIHA

AIHA
Investigation

Treatment
 AIHA
Antibodi tubuh melawan sdm sendiri
Coombs tes direk positip
AIHA panas: 37 oC, idiopatik, sekunder(SLE,
CLL,Limfoma, metil dopa)
AIHA dingin:4 oC, idiopatik, infeksi
monoklonal, poliklonal, PCH paroksismal cold
hemoglobinuri, pneumonia, mikoplasma
 mekanisme penyakit aiha
Dalam keadaan normal, eritrosit dalam sirkulasi
tidak pernah dilapisi oleh imunoglobulin (IgG
atau IgM). Tetapi pada penyakit ini, pasien
memiliki antibodi yang bereaksi dengan sel-sel
mereka sendiri.
 complement

Direct antiglobulin test

demonstrating the presence of autoantibodies (shown
here) or complement on the surface of the red blood
cell.
Mekanisme penyakit aiha
 AIHA HANGAT (WARM AIHA)
AIHA reaktif-hangat disebabkan oleh
autoantibodi IgG yg tetap berada di permukaan
eritrosit selama sel tersebut berada di sirkulasi.
Sel-sel yg dilapisi oleh antibodi beredar dan
disingkirkan secara prematur oleh limpa.
 Aiha dingin (cold aiha)
Antibodi yg hanya reaktif pada suhu rendah
tidak menimbulkan masalah klinis pada suhu
tubuh biasa. Autoantibodi dingin yg
menyebabkan penyakit klinis mungkin bekerja
optimum pada suhu 25C , 18C, atau 4C, tetapi
memperlihatkan sebagian aktivitas pada suhu
37C.
 Px:
Tanda hemolysis,
P Smear: Microspherocytosis,
Confirmation: Coombs Test / Antiglobulin test
 Auto-Immune Hemolytic anemia
Treatment:
Correct the underlying cause
Prednisolone 1mg/kg po until Hb reaches
10mg/dl then taper slowly and stop
Transfusion: for life threatening problems
Splenectomy
Immunosuppressive: Azathioprine,
Cyclophosphamide
 Acquired hemolysis
2.Infection
F. malaria: intravascular hemolysis: severe
called Blackwater fever
3.Chemical/Drugs: oxidant denaturation of
hemoglobin
Eg: Dapsone, sulphasalazine, Arsenic gas,
Cu, Nitrates & Nitrobenzene
 Non-Immune Acquired Hemolytic
Anemia
1. Mechanical Trauma
A). Mechanical heart valves
B). Arterial grafts: cause shear stress damage
C). Thermal injury: burns
D). Microangiopathic hemolytic anemia (MAHA):
by passage of RBC through fibrin strands
deposited in small vessels disruption of RBC
eg: DIC, Malignant HTN
TRAUMATIC HEMOLYSIS
 Neonatal jaundice

What is jaundice?
 Physiological jaundice
Physiological jaundice is jaundice that is present
between day 2 and day 10
 Gejala Klinik HDN

Gejala Klinik :
1. HDN ringan bayi kelihatannya sehat seperti
normal pada waktu dilahirkan 24 jam
kemudian mulai kuning.
2. HDN berat bayi sudah pucat dan anemia
berat pada waktu dilahirkan
 Causes of neonatal jaundice

Early Intermediate Late/prolonged

Haemolytic causes: Physiological jaundice Conjugated (dark urine, pale
Rh isoimmunisation Breast milk jaundice stools):
(erythroblastosis (inadequate intake) Bile duct obstruction
foetalis) Sepsis Biliary atresia
ABO incompatibility Neonatal hepatitis
Haemolysis
G6PD deficiency
Crigler-Najjar syndrome Unconjugated:
(glucuronyl transferase
Congenital infection Physiological
absent/reduced)
Breast milk jaundice
Polycythaemia, bruising
Infection
Hypothyroidism