Bimbingan UKMPPD (UKDI) - Interna 3 (Hematoonkologi)

HEMATOONKOLOGI

BIMBEL UKDI MANTAP dr. Anindya K. Zahra dr. Gandhi Anandika Febryanto dr. Alexey Fernanda N.

RBC

1

Anemia?

• Gejala anemia secara umum – lemah, lesu, letih, lelah, penglihatan berkunang-kunang, pusing, telinga berdenging dan penurunan konsentrasi.

Approach to Anemia: MCV!

Thalassemia

N Sideroblastik Mikrositik Hipokromik

Besi Serum

MCV 

Anemia

Normositik normokromik



Retikulosit



MCV Normal

Defisiensi folat Makrositik

MCV 

N/

Defisiensi Besi Penyakit Kronik Anemia hemolitik Perdarahan Akut Anemia Aplastik Leukemia, etc

Defisiensi B12

Morfologi Darah Tepi (MDT)

Anisositosis Mikrositik (8 mikron) MCV tinggi

• Anemia megaloblastik • Anemia pernisiosa

Poikilositosis Sferosit

• Sferositosis

herediter

Elliptosis (Ovalosit) Sel pensil

• Thalassemia

• Anemia defisiensi besi

Poikilositosis Sel Target (Mexican Hat cell, bull’s eye cell)

• Thalassemia • Penyakit hati kronik

Stomatosit

• Stomatosis herediter • Keracunan timah • Alkoholisme akut

Poikilositosis Sel Sabit (sickle cell; drepanocyte; cresent cell; menyscocyte)

• Hemoglobinopati

Schystosit ( fragmented cell; keratocytes)

• Anemia hemolitik • Penyakit keganasan

Poikilositosis Sel Spikel Akantosit (Spurr cell)

• Penyakit hati dengan anemia hemolitik • Paska splenektomi

Echynocyte (Burr cell, Crenated cell, sea-urchin cell)

• Penyakit ginjal menahun (uremia) • Defisiensi piruvat kinase

Anemia Mi-Hi

Anemia Mi-Hi

ADB

Angular cheilitis / stomatitis angularis peradangan sudut mulut

Koilonychia – brittle spoon-shaped nail

Papil lidah atrofi  Smooth tongue

ADB – Apusan Darah Tepi

ADB: Mikrositik hipokromik (central pallor >>), Pencil cell (+)

Normal

Terapi ADB Lini Pertama  Terapi Besi Oral • Ferro sulfat  mengandung 20 % besi elemental • Sediaan 200 mg, 325 mg (65 mg besi elemental) • Ferro fumarat  mengandung 33 % besi elemental • Sediaan 325 mg (107 mg besi elemental) • Ferro glukonat  mengandung 12 % besi elemental • Sediaan 325 mg (39 mg besi elemental)

3 – 4x sehari dengan besi elemental 50 – 65 mg (3-6 mg besi elemental/kg/hari) • Ferro sulfat 3 x 200 mg, 3 x 325 mg

Target : Hb meningkat 1 g/dL dalam 2-3 minggu Hb terkoreksi  lanjutkan terapi besi oral hingga 3-4 bulan (untuk mengembalikan cadangan besi)

Oral Iron Therapy  • • • •

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

 • • • •

Daging Senyawa sitrat Fruktosa Asam askorbat

• Efek samping Fe  Gastric upset (mual, muntah) dan konstipasi • Intoleransi terutama berkaitan dengan besarnya kadar zat besi terlarut yang ada dalam lumen usus  dapat dicegah dengan memberikan dosis awal yang rendah (misal : sulfat ferosus 3x100 mg) atau memberikan preparat besi oral bersama dengan makan

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

Approach to Anemia: MCV!

Thalassemia

N Sideroblastik Mikrositik Hipokromik

Besi Serum

MCV 

Anemia

Normositik normokromik



Retikulosit



MCV Normal

Defisiensi folat Makrositik

MCV 

N/

Defisiensi Besi Penyakit Kronik Anemia hemolitik Perdarahan Akut Anemia Aplastik Leukemia, etc

Defisiensi B12

9

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

Hemolisis

Letak

Extravascular (90%)

Intravascular (10%)

Reticuloendothelial (RE) system

Penyebab

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 • Splenectomy 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  berfungsi untuk menyediakan jumlah glutathion tereduksi (GSH) GSH  berperan sebagai scavenger terhadap metabolit oksidatif di dalam RBC, sebagai sumber NADPH yang melindungi sel dari stress oksidatif

Anemia Defisiensi G6PD

G6PD Deficiency

Anemia Defisiensi G6PD

Harrison’s Principles of Internal Medicine 17 Edition, Part 7 Oncology & Hematology, Section 2 Hematopietic Disorders

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 – FACIES COOLEY

Thalasemia – Transfusi PRC Indikasi • Hb < 8 g/dL • Hb > 8 g/dL, bila keadaan umum kurang baik, anoreksia, gangguan aktivitas, gangguan pertumbuhan, adanya pembesaran limpa yang cepat, dan perubahan pada tulang

Pemberian dan kecepatan pemberian • Diberikan sampai target Hb 12 g/dL, tidak boleh melebihi 15 g/dL • Bila Hb > 5 g/dL berikan 10-15 mL/kg/kali dalam 2 jam atau 20 mL/kg/kali dalam 3-4 jam • Bila Hb < 5 g/dL berikan 5 mL/kg/kali dengan kecepatan 2 mL/kg/jam. Beri oksigen

Pemantauan dan kontrol • Kontrol 2-4 minggu sekali bagi penderita thalasemia lama • Kadar ferritin dan besi serum diperiksa tiap 6 bulan • Fungsi organ dipantau tiap 6 bulan • Pemeriksaan marker hepatitis B dan C

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 Agent (Deferoxamine/Deferiprone/Deferiprox/ICL670 )

+ IRON CHELATING

TRANSFUSI PRC BERKALA

Indikasi iron chelating agent - Ferritin >1000 mg/dL & saturasi transferrin serum >50 % - Transfusi >5 L, transfusi >10 kali, transfusi > 1 tahun

Deferiprox = 75 mg/kg/hari, dibagi 3 dosis, per oral

Thalassemia – Indikasi Splenektomi • Limpa terlalu besar (Schuffner IV-VIII atau >6 cm)  risiko ruptur • Hipersplenisme dini : jika jumlah transfusi >250 mL/kg dalam 1 tahun terakhir • Hipersplenisme lanjut : pansitopenia Splenektomi dilakukan pada usia >5 tahun () , PT (>>), APTT (>>) , platelet count (), AT III (400.000/mm3 2. Leukositosis >12.000/mm3 (tanpa demam/infeksi) 3. Leukocyte alkaline phosphatase score >100 4. Serum vitamin B12 >900 pg/ml atau serum UB12BC >2.200 pg/ml

KRITERIA DIAGNOSIS PV

A1 + A2+ A3 atau A1 + A2 + 2 kategori B

KEGANASAN HEMATOLOGI

Leukemia CBC

Hb AL AT

Acute

Chronic

 (anemia

 (anemia)

 (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 15% – Acute/Blast crisis: blast >30% (mirip AML)

Chronic Myeloid Leukemia • 90% of patients with CML have a chromosome abnormality known as Philadelphia( Ph) chromosome in the leukaemic blasts. It results from translocation between 9 and 22 chromosomes t( 9,22). This translocation can be detected by cytogenetics or polymerase chain reaction (PCR)

Chronic Lymphoid Leukemia • Leucocytic count is 50-200x109/L or higher, the absolute lymphocyte is > 5x109/L and may be up to 300x109/L. Between 70-99% of white cells in the blood film appear as small lymphocytes

Lymphoma Maligna : Hodgkin & NonHodgkin(85%)

B symptoms (+) in Hodgkin. NHL  B symptoms (+) in advance & late stage

Lymphoma Hodgkin VS Non-Hodgkin Lymphoma Hodgkin

Lymphoma Non-Hodgkin

Dijumpai gambaran sel B neoplastik raksasa (Reed Sternberg) Gambaran klinis tampak lebih jelas dan bermanifestasi sistemik Pola penyebaran teratur ke jaringan sekitar

Penyebarannya difus (tidak teratur)

Jarang mengenai limfonodi mesenterium dan cincin Walldeyer

Sering mengenai limfonodi mesenterium dan cincin Walldeyer

Jarang mengenai sistem di luar kelenjar getah bening

Sering ekstranodal

Terlokalisasi dan sering mengenai 1 kelenjar getah bening

Mengenai banyak kelenjar getah bening

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

Hodgkin Lymphoma

TERIMA KASIH