HAEMOLYTIC

ANAEMIA
Dairion Gatot, Savita Handayani
Divisi Hematologi-Onkologi Medik
Departemen Ilmu Penyakit Dalam FK-USU/
RS H.Adam Malik, Medan 2011

WHEN

Hb 9 g%

BY

transfusion

No sign of bleeding

HEMOLYTIC ?

THEN

Hb 4 g%

Definition
Any situation in which there is a
reduction in RBC life-span due to
increase RBC destruction. Failure of
compensatory marrow response
results in anemia. Predominant site
of RBC destruction is red pulp of the
spleen.

Used Drug or
traditional
medicine

Hb
decreased

no sign of bleeding

Hemolytic ?

Infection

Anemia +
icterus (mild)

Hemolytic ?

INTERPRETATION

LABORATORY TEST

NORMOCYTIC
ANAEMIA

PERIPHERAL SMEAR
RETICULOCYTE
COUNT

INCREASE
D

BLOOD IN STOOL OR
OTHER SOURCE OF
BLEEDING
IDENTIFIED

POSITIV
E

ANTIHUMAN GLOBULIN
(COOMBSTEST)

REDUCED

NEGATIVE

POSITIVE

NEGATIVE

NEGATIVE

BONE MARROW AND

BONE MARROW BIOPSY

HYPERCELLULA
R ERYTHROID
HYPERPLASIA

HYPERCELLULA
R ERYTHROID
HYPERPLASIA

DECREASED
CELLULARITY

DIAGNOSIS

AUTO IMMUNO
HAEMOLYTIC
ANAEMIA

OTHER HAEMOLYTIC
ANAEMIAS

OTHER

BLOOD
LOSS
ANAEMIA

Erythroblastosi
s
foetalis
Transfusion
reaction
Collagen
vascular
disease

Parasites

Renal
disease

Hypersplenism

Infection

Microangiopathic

Malnutrition

haemolysis
Hereditary
spherocytosis
Paroxysmal noctural
haemoglobinuria
Enzyme deficiencies
Drug or toxin
Haemoglobinopathies

Aplastic
anaemia
Radiation

REPLACEMENT
OF NORMAL
MARROW
ELEMENTS
MYELOPHTHISIC
Tumor
Myelofibrosis
Infection
Leukaemia

normositic normochromic
anemia

Diagnostic:
MCV 80-100 fL and
MCH > 27 pg or MCHC 30 g/dL
Cause :
Distribution failure .
Lack of production,
Rate of RBC destruction
reduced red-cell life span

Haemolytic
anaemia

Rate of RBC destruction

RBC production
Reticulocyte counts

Classification of Hemolytic
anemias
Red cell abnormality
(Intracorpuscular factors)
I.

A. Hereditary
1. Membrane defect (spherocytosis,
elliptocytosis)
2. Metabolic defect (Glucoze-6-PhosphateDehydrogenaze
(G6PD) deficiency, Pyruvate kinase (PK)
deficiency)
3. Hemoglobinopathies (unstable hemoglobins,
thalassemias, sickle cell anemia )

II. Extracorpuscular factors

A. Immune hemolytic anemias
1. Autoimmune hemolytic anemia
- caused by warm-reactive antibodies
- caused by cold-reactive antibodies
2. Transfusion of incompatible blood
B. Nonimmune hemolytic anemias
1. Chemicals
2. Bacterial infections, parasitic infections
(malaria),
venons
3. Hemolysis due to physical trauma
- hemolytic - uremic syndrome (HUS)
- thrombotic thrombocytopenic purpura
(TTP)

Mechanisms of hemolysis:
-

Intravascular
- Extravascular

Inravascular hemolysis (1):

- red cells destruction occurs in vascular space
- clinical states associated with Intravascular
hemolysis:
acute hemolytic transfusion reactions
severe and extensive burns
paroxysmal nocturnal hemoglobinuria
severe microangiopathic hemolysis
physical trauma
bacterial infections and parasitic
infections (sepsis)

Inravascular hemolysis (2):

- laboratory signs of intravascular hemolysis:
indirect hyperbilirubinemia
erythroid hyperplasia
hemoglobinemia
methemoalbuminemia
hemoglobinuria
absence or reduced of free serum
haptoglobin
hemosiderinuria

INTRAVASCULAR HAEMOGLOBIN
DEGRADATION
Free Hb in blood
Haptoglobin (102
mg/dL)
Hb-haptoglobin
extravascular)
Hb
dimers
kidney

Urine
haemoglobi
n

liver (catabolism same as

in excess of
haptoglobin
Methaemoglobi
n

globin
tubular
pool
reabsorptio
Heme
n
(Fe+++)
Urine
haemosideri
n

haemopexi
n
albumi
n

amino acid

haemopexinheme
methemalbumin
albumi
hemen
RE cells in

Extravascular hemolysis :
- red cells destruction occurs in
reticuloendothelial system
- clinical states associated with
extravascular hemolysis :
autoimmune hemolysis
delayed hemolytic transfusion
reactions
hemoglobinopathies
hereditary spherocytosis
hypersplenism
hemolysis with liver disease

Extravascular hemolysis (2):

Laboratory signs of extravascular hemolysis:
indirect hyperbilirubinemia
increased excretion of bilirubin by bile
erythroid hyperplasia
hemosiderosis

EXTRAVASCULAR HAEMOGLOBIN
DEGRADATION
Haemoglobi
n

plasma protein
and amino acid
pool

Heme + globin

Macropha
ge

lungs
Biliverdin + CO + Fe

transferrin +
Fe

Bone
marrow

Bilirubi
n
plasma
albumin
Bilirubin-Albumin
(unconjugated)
liver
Bilirubin diglucuronide
(conjugated)
bile duct to
duodenum
Urobilinogen
Blood
stool
Urobilinogen +

kidney
Urobilinogen
(urine)

Hemolytic anemia - clinical

features:
- pallor

- jaundice
- splenomegaly

Laboratory features:
1. Laboratory features
- normocytic/macrocytic, hyperchromic
anemia
- reticulocytosis
- increased serum iron
- antiglobulin Coombs test is positive
2. Blood smear
- anisopoikilocytosis, spherocytes
- erythroblasts
- schistocytes
3. Bone marrow smear
- erythroid hyperplasia

LABORATORY
1. BLOOD FILM
Microspherocyte : 1. Autoimmuno haemolytic
anaemia
(AIHA)
2. Hereditary spherocytosis
3. Haemoglobinopathies : HbC
4. Hipersplenisme
MCV

MCH

MCHC

Spherocyte

AIHA

LABORATORY
RBC abnormalities
Sel target

: HbC

Fragmented RBC : schistocytes

burr cells
helmet cells (MAHA)
Plasmodium

P. falciparum

HbC

Helmet cells

Burr cells

LABORATORY
2. BONE MARROW
Erythroid hyperplasia : rubrisit
predominant
Iron stores

: negative /

or

DIAGNOSIS OF HEMOLYTIC ANAEMIA

Basic steps are :
1. Evaluation of clinical information from a
review of the history & physical
examination
2. Evaluation of the basic blood examination &
specialized laboratory examination
3. Bone marrow examination

Diagnosis of hemolytic syndrome:

1. Anemia
2. Reticulocytosis
3. Indirect hyperbilirubinemia

Autoimmune hemolytic anemia caused by

warm-reactive antibodies:
I. Primary
II. Secondary
1. acute
- viral infections
- drugs ( -Methyldopa, Penicillin, Quinine,
Quinidine)
2. chronic
- rheumatoid arthritis, systemic lupus
erythematosus
- lymphoproliferative disorders
(chronic lymphocytic leukemia,
lymphomas,

Autoimmune hemolytic anemia caused by

cold-reactive antibodies:
I. Primary cold agglutinin disease
II. Secondary hemolysis:
- mycoplasma infections
- viral infections
- lymphoproliferative disorders
III. Paroxysmal cold hemoglobinuria

Autoimmune hemolytic
anemia diagnosis
- positive Coombs test

Kriteria Diagnosis AIHA

Direct Coombs test positif (C3b &/ anti IgG pada eritrosit).
Perexclusionem menyingkirkan kemungkinan AIHA sekunder:
Anamnesis obat-obatan, alkohol, bahan kimia (Occupational
disease), adakah keganasan ?,
Pemeriksaan serologi virus dan bakteria misalnya Dengue, CMF,
EBV, HIV, Rubella,
Pemeriksaan ACA untuk mengetahui adanya Sindroma Anti
Fosfolipid (APS),
Pemeriksaan Rematoserologi, C3 dan C4, ANA, Anti dsDNA
(Penyakit Auto Immun),
Pemeriksaan Coombs apakah ada IgG/IgM atau C3b pada eritrosit
dan/atau antibodi terhadap eritrosit, jenis reaktifitas cold type jika
bereaksi pada suhu 20oC
Pemeriksaan sidikan hati, limpa, KGB mediastinum dan para aorta
(Limfoma Non Hodgkins),
Pemeriksaan Immunoelektroforesis protein (Penyakit proliferasi sel
B limfosit atau plasma),
BMP Aspirasi dan Biopsi untuk menilai adanya Penyakit
limfoproliferasi non sekretorik.

Treatment:
- steroids
- splenectomy
- immunosupressive agents
- transfusion

G-6PD deficiency
G6-PD
activity

G-6PD deficiency
X-linked disorders, heterozygote females
only
rarely have significant haemolysis
Haemolysis cause by infection, acidosis,
drugs & toxins
Red blood cells membrane oxidation
Precipitation of haemoglobin
bodies
PB smear

Heinz

bite cells

In acute haemolytic episode G-6PD activity

maybe normal

Diagnosis

Low level G-6PD concentration

Treatment :
1. Avoid of drugs exposure.
2. Transfusion .
3. No spesific treatment.
4. Anti oksidan, ???.

Drug exposure of hemolytic.

Asetanilid
Furazolidon
Biru metilen
Asam nalidixat
Naftalen
Nitrofurantoin
Fenazopirid
Fenilhidrazin

primakuin
sulfasetamid
sulfametoksazol
sulfanilamid
sulfapiridin
biru toluidin
trinitrotoluen
jamu

Hereditary microspherocytosis (1)

1. Pathophysiology
- red cell membrane protein defects (spectrin
deficiency)
resulting cytoskeleton instability
2. Familly history
3. Clinical features
- splenomegaly
4. Laboratory features
- hemolytic anemia
- blood smear-microspherocytes
- abnormal osmotic fragility test
- positive autohemolysis test
- prevention of increased autohemolysis by including
glucose in
incubation medium
5. Treatment
- splenectomy

Osmotic fragility test

A : congenital non-spherocytic
anaemias
B : spherocytosis

Hereditary microspherocytosis (2)

5. Treatment :
Splenectomy

Paroxysmal nocturnal hemoglobinuria

(PNH).

1. Pathogenesis
- an acquired clonal disease, arising from a
somatic mutation in a
single abnormal stem cell
- glycosyl-phosphatidyl- inositol (GPI) anchor
abnormality
- deficiency of the GPI anchored membrane
proteins
(decay-accelerating factor =CD55 and a
membrane inhibitor
of reactive lysis =CD59)
- red cells are more sensitive to the lytic effect of
complement

3. PNH laboratory features:

- pancytopenia
- chronic urinary iron loss
- serum iron concentration decreased
- hemoglobinuria
- hemosiderinuria
- positive Hams test (acid hemolysis test)
- positive sugar-water test
- specific immunophenotype of erytrocytes
(CD59, CD55)

HAMS & SUGAR WATER TEST

Paroxymal nocturnal haemoglobinuria (PNH)

RBC in PNH are abnormally sensitive to

lysis to complement

Diagnosis can be made by :

1. Abnormal lysis of RBC by acidic serum
(Hams tests)
2. Hypotonic medium solution (Sugar
water test)

4. Treatment :
- washed RBC transfusion
- iron therapy
- allogenic bone marrow transplantation

Haemolytic crisis
Increased rate of haemolysis
Reticulocytosis
Painful crisis

stasis blood vessel

auto splenectomia
priapism
retinopathy
necrosis papilla

renalis