bimbingan ukmppd (ukdi) - interna 3 (hematoonkologi)

7/26/2019 Bimbingan UKMPPD (UKDI) - Interna 3 (Hematoonkologi)

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BIMBEL UKDI MANTAP

dr. Anindya K. Zahra

dr. Gandhi Anandika Febryantodr. Alexey Fernanda N.

HEMATOONKOLOGI


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RBC1


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Anemia?

Gejala anemia secara umum

lemah, lesu, letih, lelah, penglihatan berkunang-kunang,pusing, telinga berdenging dan penurunan konsentrasi.


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Anemia

Mikrositik

Hipokromik Besi Serum

N

Thalassemia

Sideroblastik

DefisiensiBesi

PenyakitKronik

Normositiknormokromik

Retikulosit

Anemiahemolitik

PerdarahanAkut

N/

AnemiaAplastik

Leukemia, etcMakrositik

Defisiensifolat

Defisiensi

B12

MCV

MCV Normal

MCV

Approach to Anemia: MCV!


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Morfologi Darah Tepi (MDT)


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Anisositosis

Anemia defisiensi besi

Anemia akibat penyakit

kronik

Keracunan tembaga

Anemia sideroblasik

Anemia megaloblastik

Anemia pernisiosa

Mikrositik (8 mikron)

MCV tinggi


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Poikilositosis

Sferosit

Thalassemia

Anemia defisiensi besi

Elliptosis (Ovalosit)

Sel pensil

Sferositosis herediter


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Poikilositosis

Sel Target (Mexican Hat cell,

bulls eye cell)

Thalassemia

Penyakit hati kronik

Stomatosit

Stomatosis herediter

Keracunan timah

Alkoholisme akut


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Poikilositosis

Sel Sabit (sickle cell;

drepanocyte; cresent cell;

menyscocyte)

Hemoglobinopati

Schystosit (fragmented cell;

keratocytes)

Anemia hemolitik

Penyakit keganasan


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Poikilositosis

Sel Spikel

Echynocyte(Burr cell, Crenated

cell, sea-urchin cell)Akantosit (Spurr cell)

Penyakit hati dengan

anemia hemolitik

Paska splenektomi

Penyakit ginjal menahun

(uremia)

Defisiensi piruvat kinase


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Anemia Mi-Hi


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Anemia Mi-Hi


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16/107Koilonychiabrittle spoon-shaped nail

Angular cheilitis / stomatitis angularis

peradangan sudut mulut

Papil lidah atrofiSmooth tongue

ADB


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ADB: Mikrositik hipokromik

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

Normal

ADBApusan Darah Tepi


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Terapi ADB

Lini PertamaTerapi Besi Oral

Ferro sulfatmengandung 20 % besi elemental

Sediaan 200 mg, 325 mg (65 mg besi elemental)

Ferro fumaratmengandung 33 % besi elemental

Sediaan 325 mg (107 mg besi elemental)

Ferro glukonatmengandung 12 % besi elemental

Sediaan 325 mg (39 mg besi elemental)

34x sehari dengan besi elemental 5065 mg (3-6 mg besielemental/kg/hari)

Ferro sulfat 3 x 200 mg, 3 x 325 mg

Target : Hb meningkat 1 g/dL dalam 2-3 minggu

Hb terkoreksilanjutkan terapi besi oral hingga 3-4 bulan (untukmengembalikan cadangan besi)


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Oral Iron Therapy

Efek samping Fe Gastric upset (mual, muntah) dan konstipasi

Intoleransi terutama berkaitan dengan besarnya kadar zat besiterlarut yang ada dalam lumen ususdapat dicegah denganmemberikan dosis awal yang rendah(misal : sulfat ferosus 3x100

mg) atau memberikan preparat besi oral bersama dengan makan

Antasida

Fitat (pada sereal) Tanin (pada teh)

Fosfat

Daging

Senyawa sitrat Fruktosa

Asam askorbat


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Anemia Mi-Hi

Th l i k dib h di


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Thalassemia akan dibahas dianemia hemolitik


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Anemia Sideroblastik

Genetic(X-linkedor AD) oracquired(myelodysplasiasyndrome)

Sideroblast:nucleatederythroblast

Ring: iron inperinuclear

mithocondria Iron (+) but

cannot corporateit to Hb

Bone marrow aspirate: ring sideroblast


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Anemia

Mikrositik

Hipokromik Besi Serum

N

Thalassemia

Sideroblastik

DefisiensiBesi

PenyakitKronik


Retikulosit

Anemiahemolitik

PerdarahanAkut

N/

AnemiaAplastik


Defisiensifolat

DefisiensiB12

MCV

MCV Normal

MCV


9


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Anemia Hemolitik

Curiga anemia hemolitik: Klinis: Anemia, Jaundice, Splenomegali

Lab: Retikulosit , Bilirubin indirek

9


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Hemolisis

Letak

Extravascular(90%)

Reticuloendothelial (RE)system

Intravascular(10%)

Penyebab

Intrinsik

Membran

Enzim

Hemoglobin

Extrinsik

Autoimun

Infeksi

Microangiopathy


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Anemia Hemolitik: Defek Intrinsik

Intrinsik

MembranHereditaryspherocyte

Osmotic fragilitytest

Enzim G6PD deficiency G6PD assay

Hemoglobin

ThalassemiaHb

elektroforesis

Sickle cell


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Intrinsik




Hemoglobin

ThalassemiaHb

elektroforesis

Sickle cell


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Membranopathy

Hereditary SpherocytosisMDTSpherocytesOsmotic fragility test

Splenectomy often very effective


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Intrinsik




Hemoglobin

ThalassemiaHb

elektroforesis

Sickle cell

Enzymopathy


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Enzymopathy

G6PD Deficiency

G6PDberfungsi untuk menyediakan jumlah glutathion tereduksi (GSH)

GSHberperan sebagai scavenger terhadap metabolit oksidatifdi dalam

RBC, sebagai sumber NADPH yang melindungi sel dari stress oksidatif


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Anemia Defisiensi G6PD


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G6PD Deficiency


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Anemia Defisiensi G6PD

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


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Intrinsik




Hemoglobin

ThalassemiaHb

elektroforesis

Sickle cell


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Hemoglobinopathy

Hemoglobin Deffect

Thalassemia

Hb elektroforesis

Sickle cell disease

Thalassemia: microcytic hypochromic anemia,

anisositosis, poikilositosis, target cell


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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


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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).


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Thalassemia


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Splenomegaly

Splenomegaly & Extramedullary hematopoiesis

FACIES RODENT FACIES COOLEY


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FACIES RODENTFACIES COOLEY


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ThalasemiaTransfusi 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 perubahanpada 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 dalam3-4 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


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Chronichemolysis

Iron overload Tissue damage

Thalassemia

Excess ironfree hydroxyl radicalsROS

Insoluble iron complexesdeposited inbody tissues

Mechanism

Pituitary impaired growth Heart cardiomyopathy, heart failure

Liver hepatic cirrhosis

Pancreas diabetes mellitus

Gonads hypogonadism, infertility

Clinical sequelae of iron overload

Iron Chelating Agent


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Iron Chelating Agent

(Deferoxamine/Deferiprone/Deferiprox/ICL670 )

TRANSFUSI PRC BERKALA

IRON CHELATING

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


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ThalassemiaIndikasi 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 (


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Anemia Hemolitik: Defek Ekstrinsik

Extrinsik

Autoimun

Warm

Cold

MicroangiopathyProstheticvalves etc

Infeksi Malaria, etc

Autoimmune Hemolytic Anemia


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Autoimmune Hemolytic AnemiaWarm & Cold AIHA

Warm (70 %) Cold (30 %)

Maximally bindRBCs at

37C 0 to 4C

Clinical Acute and severe

Collagen disease, idiopathic

Post infectious, idiopathic

Younger age group Older age group

Mediated byautoandibodies

IgG IgM(cold agglutinin)which fixescomplement (C3), antibodi Donath-

Landsteiner

Mechanism IgG-coated RBCspartially

ingested by the macrophages of

the spleenmicrospherocytes

extravascular hemolysis

IgM + RBCactivate complement

C3 coated RBCagglutination

intravascular hemolysis

Treatment Corticosteroid

Splenectomy (if steroid isnt

adequate)

Avoidance of cold

Corticosteroid and splenectomy

wasnt effective

Transfusion therapy in AIHA is challenging, and the most compatible

red blood cells should be given


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Coombs Test


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Autoimmune Hemolytic Anemia

Warm AIHA:

spherocytes

Mi i hi A i


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Microangiopathic Anemia

Cause: Microvascular disease (DIC, TTP etc) Heart valve prostheses

Trauma / implanted devices

Schistocytes and microspherocytes noted on the blood smear

f


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Anemia Defisiensi EPO

Anemia padachronic kidney

disease (CKD)

(mulai pada

stage III) Anemia

normositik

normokromik


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Anemia Aplastik

Pansitopeniayang disertaihiposelularitas sumsumtulang

Etiologi =

idiopatik (sebagian besar),

Radiasi Obat & bahan kimia

kemoterapi, benzena, gold,kloramfenikol,hidantoin,carbamazepine

Infeksi virushepatitis,

virus Ebstein-Barr, CMV,parvovirus, HIV-1

Penyakit imun

Hemoglobinuriaparoksismal nokturnal

Kehamilan


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5 L (lemah, letih, lesu, lalai, lupa)

Pucat, pusing, jantung berdebar,dispnea, penglihatan kabur, telingaberdenging

Anemia

Perdarahan mukosa

Perdarahan bawah kulit (memar)Trombositopenia

Rentan terhadap infeksi

DemamLeukopenia

Anemia AplastikManifestasi Klinis


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Anemia Aplastik

Gambaran histologis anemia aplastik pada biopsi sumsum tulang

Gambaran hiposeluler, banyak terisi lemak

ThalassemiaApproach to Anemia: MCV!


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Anemia

Mikrositik

HipokromikBesi Serum

N

Thalassemia

Sideroblastik

DefisiensiBesi

PenyakitKronik


Retikulosit

Anemiahemolitik

PerdarahanAkut

N/

AnemiaAplastik


Defisiensifolat

DefisiensiB12

MCV

MCV Normal

MCV



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Megaloblastic Anemia


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Anemia Megaloblastic Vitamin B12


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Anemia MegaloblasticVitamin B12

Deficiency

Anemia Megaloblastikukuran eritrosit

membesar dan hampir sama dengan leukosit

Tampak neutrofil dengan hipersegmentasi

Perbandingan eritrosit dan leukosit

pada keadaan normal


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Tatalaksana Defisiensi Folat & B12

Defisiensi asam folat

Asam folat 1-5 mg/hariselama 1-4 bulan

Dosis 1 mg/hari biasanyasudah efektif

Defisiensi vitamin B12

Vitamin B12 parenteral (IMatau SC) 1 mg/hari selama 1minggu

Dilanjutkan dengan 1

mg/minggu selama 4 minggu,lalu 1 mg/bulan

Sediaan oral sama efektif,tetapi membutuhkankompliansi pasien (1-2

mg/hari) Sediaan oral kurang efektif

apabila terdapat gangguanabsorpsi vitamin B12 digastrointestinal

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Komponen Darah

WholeBlood

Komponen lengkap

Perdarahan masifatau hipovolemik

Packed RedCell (PRC)

Eritrosit yangdipisahkan dari

plasma

Anemia tanpapenurunan

komponen darah lain

WashedRed Cell

PRC dicuci NaCl

fisiologis,menghilangkanantibodi yang

menempel di plasma

Penderita transfusi

berulang ataumengalami demam

pada transfusisebelumnya

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Komponen Darah

PlateletConcentrate

Trombosit

Trombositopenia,profilaksis (operasi),

Fresh FrozenPlasma

All coagulationfactor

Multiple coagulationfactor deficiency,

DIC

Cryoprecipitate

Fibrinogen, vonWillebrand factor,factor VIII, factor XIII

and fibronectin.

Haemophilia A, VonWillebrandsdisease,

Hipofibrinogenemia


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HemogramDifferential Leukocytes Count

Mulai dengan sel basofil / eosinofil / neutrofil

batang / neutrofil segmen / limfosit / monosit Nilai normal hitung jenis pada dewasa

- Basofil : 0 - 1 %

- Eosinofil : 1 3 %

- Neutrofil Batang : 2 6 %- Neutrofil Segmen : 50 70 %

- Limfosit : 20 40 %

- Monosit : 2 8 %

Stab

Neutrophil


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Bleeding timemenilai

fungsi hemostasis primer

(aktivitas platelet)

Clotting timemenilai fungsi

hemostasis sekunder (aktivitas

faktor koagulasi)

coagulation


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coagulation

cascade

waterfall

PT

APTT

TT

*

Fibrinolysis system


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Fibrinolysis system


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20


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ITP


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ITPManifestasi Klinis


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Terapi ITP


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Terapi ITP

ITP: antiplatelet antibody

platelet destruction

Indikasi : AT < 20.000 atau perdarahan

Prednisone 1 mg/kg/hari (2 minggu)

Kortikosteroid

Indikasi : severe, life-threatening bleeding, atau anak dengan AT


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Intravascu lar Coagulat ion)

Clinical manifestation of DIC


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b di i f


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Lab diagnosis of DIC

DIC Screening : bleeding time (>>) , PT (>>), APTT

(>>) , platelet count (), AT III (


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Evans Syndrome

Definisi

AIHA (direct Coombstest +) dan immune-mediatedthrombocytopenia tanpa adanya penyebab yang mendasari

Manifestasi Klinis Trombositopenia (76%), anemia (67%), neutropenia (24%),

pansitopenia (14%), hemolitik

Manajemen

Stabilisasi fungsi kardiovaskular dan respirasi

Transfusi PRC

Prednison (first line), IvIg

H h S h l i P


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Henoch-Schonlein Purpura

Definisi

Gangguan imun akut yang diperantarai oleh IgAvaskulitis general yang melibatkanpembuluh darah kulit, GI tract, ginjal, sendi, dan paru / CNS (jarang)

Manifestasi Klinis

Gejala prodromal : sakit kepala, anorexia, demam Ruam (95-100% kasus), terutama melibatkan tungkai. Lesi urtikaria atau macula

eritematosa, berkembang menjadi papul pucat lalu purpura

Nyeri perut dan muntah

Nyeri sendi, terutama di tungkai bawah dan ankle

Edema subkutan, edema skrotum

Feses berdarah

Manajemen

Suportif, analgetik, corticosteroid

H h S h l i P


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Henoch-Schonlein Purpura

Characteristic rash of Henoch-Schnlein purpura.


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P li it i


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Polisitemia

P li it i V


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Polisitemia Vera

Kelainan neoplastik yang ditandai dengan peningkatan eritorosit (disertaidengan leukositosis dan trombositosis)

Sering tidak bergejala (asimptomatik)

Peningkatan volume dan viskositas eritrositsakit kepala, malaise,dyspnea, fatigue, gangguan penglihatan

Peningkatan turnoversel darahhiperurisemiarisiko gout dan batu

saluran kemih

Hiperviskositastrombosisstroke, TIA, DVT, infark miokard, oklusiarteri vena retina

Polisitemia


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Polisitemia

K it i PV l h PVSG


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Kriteria PV oleh PVSG

KATEGORI A KATEGORI B

1. Total volume RBC 36 ml/kg pada

pria, 32 ml/kg pada pria

2. SaO2 > 92%

3. Splenomegali

1. Trombositosis >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


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KEGANASAN HEMATOLOGI

Le kemia


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LeukemiaCBC Acute Chronic

Hb (anemia (anemia)

AL (leukositosis) (leukositosis)

AT (trombositopenia) - N/- in CML blast crisis

Diff count blast cells (nucleoli (+)) immature granulocytes (allstage of maturation)

Myeloid (AML) Lymphoid (ALL) Myeloid

(CML)

Lymphoid CLL

80-90% caseAdult & children

Myeloblast >20%

Auer rod (+)

Children>>

Limfoblast >20%

AdultsPhiladelphia

chromosom

>55 yoLimfositosis

>50rb

*Pansitopenia may present in the early sign of leukemia


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Auer rod

nucleoli

AML M1:

AML without

maturation

Myeloblast > 80-90%

AML-M3


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AML-M3

Hypergranular: consist of procoagulant

(promote coagulation activity)induce DIC

Multiple Auer rod

promyelocytes


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ALL-L1: small uniform cells

ALL-L3: large varied cells with

strongly basophilic cytoplasm &

vacuoles (bubble-like features)

ALL-L2: varied cell, large blast cells

with prominent nucleoli & cytoplasm

and with more heterogeneity

ALL-L1: uniform cell, small blast cell

with scanty cytoplasm


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Blast

transformationAccelerated

phase

Chronic

phase

biphasic

triphasic

several years

several years

Fase:

Kronik: blast 15%

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

Chronic Myeloid Leukemia


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Chronic Myeloid Leukemia

90% of patients with CML have a chromosomeabnormalityknown as Philadelphia( Ph)

chromosomein the leukaemic blasts. It results

from translocation between 9 and 22chromosomes t( 9,22). This translocation can

be detected by cytogenetics or polymerase

chain reaction (PCR)


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Chronic Lymphoid Leukemia


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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 smalllymphocytes

Lymphoma Maligna : Hodgkin & Non-

Hodgkin(85%)


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Hodgkin(85%)

B symptoms (+) in Hodgkin.

NHLB symptoms (+) in

advance & late stage

Lymphoma Hodgkin VS Non Hodgkin


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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 teraturke 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 kelenjargetah bening

Sering ekstranodal

Terlokalisasi dan sering mengenai 1

kelenjar getah bening

Mengenai banyak kelenjar getah bening

Hodgkin Lymphoma


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Hodgkin Lymphoma

Owls EyesReed Stenberg cell (+)

Hodgkin Lymphoma


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Hodgkin Lymphoma


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TERIMA KASIH

bimbingan ukmppd (ukdi) - interna 3 (hematoonkologi)

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