HEMATOONKOLOGI

BIMBEL UKDI MANTAP

dr. Anindya K Zahra

RBC

Anemia?

Approach to Anemia: MCV!

Mikrositik
Hipokromik

ADB

Penyakit
kronik

Besi Serum
Thalassemia

MCV

N
Sideroblastik

Anemia

Normositik
normokromik

Restikulosit

MCV Normal

Anemia
hemolitik
Perdarahan
Akut

Aplastik
Defisiensi
folat

Makrositik

MCV

N/
Leukemia, etc

Defisiensi
B12

MDT

Anemia Mi-Hi

Anemia Mi-Hi

ADB

Angular cheilitis

Smooth tongue
Koilonychia brittle spoon-shaped nail

ADB

ADB: Mikrositik hipokromik

(central pallor >>), Pencil cell (+)

Normal

Terapi ADB
First line: Oral iron therapy
Ferrous sulphate 3x200 mg
Ferrous sulfate 325 mg = 65 mg elemental iron
Ferrous gluconate 325 mg = 38 mg elemental iron.
Bone marrow response to iron is limited to 20 mg per day of
elemental iron

Target: Hb increase of 1 g/dL every 2-3 weeks

Hb corrected iron stores return to normal (~4 months)

Oral Iron Therapy

Antasida
Fitat (pada sereal)
Tanin (pada teh)
Fosfat

Daging
Senyawa sitrat
Fruktosa
Asam askorbat

Efek samping Fe Gastric upset. Intoleransi terutama berkaitan

dengan besarnya kadar zat besi terlarut yang ada dalam lumen usus
dapat dicegah dengan memberikan dosis awal yang rendah.

Anemia Mi-Hi

Thalassemia akan dibahas di

anemia hemolitik

Anemia Sideroblastik
Genetic (X-linked
or AD) or acquired
(myelodysplasia
syndrome)
Sideroblast:
nucleated
erythroblast
Ring: iron in
perinuclear
mithocondria
Iron (+) but
cannot corporate
it to Hb

Bone marrow aspirate: ring sideroblast

Anemia Mi-Hi

Megaloblastic Anemia

Anemia megaloblastic

Anemia Hemolitik
Curiga anemia hemolitik:
Klinis: Anemia, Jaundice, Splenomegali
Lab: Retikulosit , Bilirubin indirek

Hemolisis

Letak

Extravascular
(90%)

RE system

Penyebab

Intravascular
(10%)

Intrinsik

Extrinsik

Membran

Autoimun

Enzim

Infeksi

Hemoglobin

Microangiopathy

Anemia Hemolitik: Defek Intrinsik

Intrinsik

Membran

Hereditary
spherocyte

Osmotic fragility
test

Enzim

G6PD deficiency

G6PD assay

Thalassemia

Hb
elektroforesis

Hemoglobin
Sickle cell

Anemia Hemolitik: Defek Intrinsik

Intrinsik

Membran

Hereditary
spherocyte

Osmotic fragility
test

Enzim

G6PD deficiency

G6PD assay

Thalassemia

Hb
elektroforesis

Hemoglobin
Sickle cell

Membranopathy

Hereditary Spherocytosis
MDT Spherocytes
Osmotic fragility test
Slenectomy often very effective

Anemia Hemolitik: Defek Intrinsik

Intrinsik

Membran

Hereditary
spherocyte

Osmotic fragility
test

Enzim

G6PD deficiency

G6PD assay

Thalassemia

Hb
elektroforesis

Hemoglobin
Sickle cell

Enzymopathy
G6PD Deficiency

G6PD Deficiency

G6PD Deficiency

Anemia Hemolitik: Defek Intrinsik

Intrinsik

Membran

Hereditary
spherocyte

Osmotic fragility
test

Enzim

G6PD deficiency

G6PD assay

Thalassemia

Hb
elektroforesis

Hemoglobin
Sickle cell

Hemoglobinopathy
Hemoglobin Deffect
Thalassemia
Hb elektroforesis

Thalassemia: microcytic hypochromic anemia,

anisositosis, poikilositosis, target cell

Sickle cell disease

What is thalassemia?

Inherited disorders
Defective hemoglobin chains
The two main types:
Alpha
Beta more severe

Hb Elektroforesis HbA2 & HbF

Suspect thalassemia if:

Family history (+)

Microcytic anemia
Jaundice
Bone deformities
Splenomegaly
Appearance early in life

a Thalassemia minor: often no target cells, but an increase in the number of small erythrocytes
(shown here in comparison with a lymphocyte), so that sometimes there is no anemia.
b More advanced thalassemia minor: strong anisocytosis and poikilocytosis (1), basophilic
stippling (2), and sporadic target cells (3).

Thalassemia

Splenomegaly

Splenomegaly &Extramedullary hematopoiesis

FACIES RODENT

Thalassemia
Chronic
hemolysis

Iron overload

Tissue damage

Mechanism
Excess iron free hydroxyl radicals ROS
Insoluble iron complexes deposited in
body tissues
Clinical sequelae of iron overload

Pituitary impaired growth

Heart
cardiomyopathy, heart failure
Liver
hepatic cirrhosis
Pancreas diabetes mellitus
Gonads hypogonadism, infertility

Iron Chelating
(Deferoxamine/Deferiprone/ICL670 )

IRON CHELATING

TRANSFUSI PRC BERKALA

Anemia Hemolitik: Defek Ekstrinsik

Warm
Autoimun
Cold

Extrinsik

Microangiopathy

Infeksi

Prosthetic
valves etc

Malaria, etc

Autoimmune Hemolytic Anemia

Warm & Cold AIHA
Warm

Cold

Maximally bind
RBCs at

37C

0 to 4C

Clinical

Acute and severe

Collagen disease, idiopathic

Post infectious, idiopathic

Younger age group

Older age group

Mediated by
autoandibodies

IgG

IgM which fixes complement

(C3)

Mechanism

IgG-coated RBCs partially

ingested by the macrophages of
the spleen microspherocytes
extravascular hemolysis

IgM + RBC activate

complement C3 coated RBC
agglutination
intravascular hemolysis

Treatment

Corticosteroid
Splenectomy

Avoidance of cold

Transfusion therapy in AIHA is challenging, and the most compatible

red blood cells should be given

Coombs Test

AIHA
Warm AIHA:
spherocytes

Microangiopathic Anemia

Schistocytes and microspherocytes noted on the blood smear

Cause:
Microvascular disease (DIC, TTP etc)
Heart valve prostheses
Trauma / implanted devices

16

Deep Vein Thrombosis

VIRCHOW
FR
WELLS

Wells Score

18

Komponen darah
Platelet
Concentrate

Fresh Frozen
Plasma

Cryoprecipitate

Trombosit

All coagulation
factor

Fibrinogen, von
Willebrand factor,
factor VIII, factor XIII
and fibronectin.

Trombositopenia,
profilaksis (operasi),

Multiple coagulation
factor deficiency,
DIC

Haemophilia A, Von
Willebrands
disease,
Hipofibrinogenemia

20

ITP

Terapi ITP
ITP: antiplatelet antibody platelet destruction
Kortikosteroid
Prednisone 1-1,5mg/kg/hari

Platelet
Not indicated unless there is significant bleeding. In ITP
transfusion increments are usually poor and platelet survival is
short
Another source: Indication: AT <30.000 asymptomatic, 30.00050.000 bleeding (+).

IvIg
Indication: major bleeding, TC <5000 despite 3 days of steroid or
extensive progressive purpura

Polisitemia

Polisitemia

KEGANASAN HEMATOLOGI

Leukemia
CBC

Acute

Chronic

Hb

(anemia

(anemia)

AL
AT

(leukositosis)

(leukositosis)

(trombositopenia)

- N/
- in CML blast crisis

Diff count blast cells (nucleoli (+))

immature granulocytes (all

stage of maturation)

Myeloid (AML)

Lymphoid (ALL)

Myeloid
(CML)

80-90% case
Adult & children
Myeloblast >20%
Auer rod (+)

Adults
Children>>
Philadelphia
Limfoblast >20% chromosom

*Pansitopenia may present in the early sign of leukemia

Lymphoid CLL
>55 yo
Limfositosis
>50rb

AML M1:
AML without
maturation

Myeloblast > 80-90%

Auer rod
nucleoli

AML-M3
promyelocytes

Multiple Auer rod

Hypergranular: consist of procoagulant

(promote coagulation activity) induce DIC

ALL-L1: small uniform cells

ALL-L1: uniform cell, small blast cell

with scanty cytoplasm

ALL-L2: varied cell, large blast cells

with prominent nucleoli & cytoplasm
and with more heterogeneity

ALL-L3: large varied cells with

strongly basophilic cytoplasm &
vacuoles (bubble-like features)

Chronic
phase

several years

Blast
transformation

Accelerated
phase
triphasic
biphasic

several years

Fase:
Kronik: blast <5%
Accelerated: blast >15%
Acute/Blast crisis: blast >30% (mirip AML)

Lymphoma: Hodgkin & Non-Hodgkin(85%)

B symptoms (+) in Hodgkin.

NHL B symptoms (+) in
advance & late stage

Hodgkin Lymphoma
Owls Eyes
Reed Stenberg cell (+)

Hodgkin Lymphoma

Reed Stenberg Cell Owls Eyes

Biopsy
Excisional or incisional biopsy
In this type of biopsy, a surgeon cuts through the skin to remove the entire tumor
(called an excisional biopsy) or a small part of a large tumor (called an incisional
biopsy).

Enucleation
surgical removal of a mass without cutting into or dissecting it. Eg: eye, oral pathology,
uterine fibroids (without hysterectomy)

FNA
does not require an incision

Core biopsy
uses needles that are slightly larger than those used in FNA
Local anasthesia
Sometimes uses a special vacuum tools to get larger core biopsies from breast tissue

Terima Kasih

Clinical classification and management of thalassemia*

Homozygous disorder

Significant imbalance of / globin chains

Severe anemia presenting early in life

Requires lifelong RBC transfusions

If untreated, leads to death usually in first decade

Various genetic interactions

Globin chain production moderately impaired
Mild anemia, diagnosed usually in late childhood
Occasional blood transfusions may be required

Thalassemia
intermedia

Heterozygous condition
Asymptomatic
May require genetic counseling

Thalassemia
minor

Severity of disease

Thalassemia major

Thalassemia*

PT
APTT
coagulation
cascade

waterfall

TT

Activity of Platelet

: Bleeding Time. No longer recommended to use.

Fibrinolysis system

Clotting time
is the time required for a sample of blood to coagulate in vitro under standard
conditions.
In order for blood to clot, the enzyme thrombin must be generated from the
plasma precursor prothrombin. Thrombin then converts soluble fibrinogen
into insoluble fibrin. Generation of thrombin involves the sequential activation
of a number of other plasma clotting factor, this process is also being assisted
by Ca++ and by factors released by platelets and damaged tissues . The time
taken for blood to clot mainly reflects the time required for the generation of
thrombin in this manner. If the plasma concentration of prothrombin or of
some of the other factors is low (or if the factor is absent, or functionally
inactive), clotting time will be prolonged. The expected range for clotting time
is 4-10 mins.

Bleeding Time:
This test measures the time taken for blood vessel constriction and platelet
plug formation to occur. No clot is allowed to form, so that the arrest of
bleeding depends exclusively on blood vessel constriction and platelet action.

A sample of the patient's blood is obtained by

venipuncture. The blood is decalcified (by collecting it into
a tube with oxalate or citrate ions) to prevent the clotting
process from starting before the test. The blood cells are
separated from the liquid part of blood (plasma) by
centrifugation. The PT test is performed by adding the
patient's plasma to some source of Tissue Factor (e.g.: a
protein, thromboplastin, from homogenized brain tissue)
that converts prothrombin to thrombin. The mixture is
then kept in a warm water bath at 37C for one to two
minutes. Calcium chloride (excess quantities of ionized
calcium) is added to the mixture in order to counteract the
sodium citrate and allow clotting to start. The test is timed
from the addition of the calcium chloride until the plasma
clots. This time is called the Prothrombin Time. The
prothrombin test specifically evaluates the presence of
factors VII, V, and X, prothrombin, and fibrinogen. A
prothrombin time within the 11 -15 second range (depends
on the source of thromboplastin used) indicates that the
patient has normal amounts of the above clotting factors.
A prolonged prothrombin time indicates a deficiency in any
of factors VII, X, V, prothrombin, or fibrinogen. It may mean
that the patient has a vitamin K deficiency (vitamin K is a
co-factor in the synthesis of functional factors II
(prothrombin), VII, IX and X) or a liver disease (the liver is
the site of synthesis of the plasma protein factors). The
prothrombin time of patients receiving a vitamin Kcompeting coumarin drug such as warfarin
(anticoagulation therapy used in deep venous
thrombophlebitis) will also be prolonged, usually in the
range of one and one half to two times the normal PT time.

PT Faktor
Ekstrinsik

The activated partial thromboplastin

time (aPTT) is a test performed to
investigate bleeding disorders and to
monitor patients taking an anticlotting
drug such as heparin which inhibits
factors X and thrombin, while activating
anti-thrombin.
The aPTT test uses blood which is
decalcified to prevent clotting before
the test begins. The plasma is separated
by centrifugation. (Ionized) Calcium and
activating substances are added to the
plasma to start the intrinsic pathway of
the coagulation cascade. The
substances are: kaolin (hydrated
aluminum silicate) and cephalin. Kaolin
serves to activate the contactdependent Factor XII, and cephalin
substitutes for platelet phospholipids.
The partial thromboplastin time is the
time it takes for a clot to form,
measured in seconds. Normally, the
sample will clot in 35 seconds.

aPTT Faktor
intrinsik