Hematoonkologi

HEMATOONKOLOGI

BIMBEL UKDI MANTAP dr. Anindya K Zahra

1

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

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Megaloblastic Anemia

Anemia megaloblastic

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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

37°C

0° to 4°C

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

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Deep Vein Thrombosis • VIRCHOW • FR • WELL’S

Well’s 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 Willebrand’s disease, Hipofibrinogenemia

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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 > 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 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 “Owl’s Eyes” Reed Stenberg cell (+)

Hodgkin Lymphoma

Reed Stenberg Cell –Owl’s 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 α / β 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 37°C 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