anemia kanker
DESCRIPTION
internaTRANSCRIPT
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Dr. Mika Lumban Tobing, SpPD-KHOMSub Bagian Hematologi-Onkologi Medik
Bagian Ilmu Penyakit Dalam
FK UNDIP / RS Dr. Kariadi
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Penderita KankerPenderita Kanker
• Insidensinya meningkat• Mortalitas tinggi
Nederland penyebab kematian no. 2Penderita kanker pd wanita usia 30-60 thPenyebab kematian no. 1Komplikasi : Hiperurisemia, hiperkalsemia, anoreksia, kaheksia, efusi maligna & anemi.
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Definisi pada Anemia
• Hemoglobin :– < 13 gr/dl pada laki-laki– < 12 gr/dl pada wanita
(WHO. Ania BJJ Am Geriatr Soc; 45.825.1997)
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Dampak Anemia pada UmumnyaDampak Anemia pada Umumnya
Patofisiologi: Oksigenasi jaringan .
Gejala :• Palpitasi • “Lightheadedness”• “Exhaustion” • Fatigue• Takhikardi • Anoreksia, Nausea• Dispnoe • Berkurangnya Libido
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Efek Anemia pd Penderita Kanker
• Fatigue• Toksisitas kemoterapi • pada pasien geriatri merupakan
ancaman karena cadangan sistem organ terbatas.
• Kualitas hidup menurun
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CANCER-RELATED ANEMIA
IS EXPERIENCEApproximatelly 60% of
All Cancer Patients
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Insiden Anemia pd Kanker
• Tergantung dari :
- Jenis Kanker- Kemoterapi- Radioterapi
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Insiden Anemia pd berbagai Kanker
• Kanker Payudara : 97%• Kanker Paru (NSCLC) : 85%• Kanker Leher & Kepala : 74%• Kanker Kolorektal : 60%
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Insiden Anemia pd keganasan Insiden Anemia pd keganasan HematologiHematologi
• Acute Leukemia 78%
• Multiple myeloma 62%
• Hodgkin’s disease 43% to 77%
• Lymphoma 42% to 72%
• Chronic lymphocytic leukemia 20%
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EtiologiEtiologiPenyebab anemia pd kanker :• Anemia of chronic disease• Blood loss• Bone marrow replacement by tumor• Bone marrow supression by chemotherapy• Chemoterapy related myelodysplasia• Hypersplenism• Microangiopathic hemolytic anemia secondary to drug
treatment (Mitomycin-C)• Microangiopathic hemolitic anemia secondary to
intravascular mucin release from certain widespread adenocarcinomas.
• Immune mediated hemolysis (autoantibody produced by certain B-cell lymphoma.
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Anemia pd Penderita Kanker (APPK)
• Anemia Hipergeneratif :- Anemia Hemolitik :
• Anemia hemolitik autoimun (AIHA)• Microangiopathic hemolytic anemia (MAHA)• Carcinoma-Associated MAHA
- Anemia karena perdarahan
• Anemia Hiporegeneratif- Anemia “carential”- Anemia mieloptisik- Anemia aplastik & sekunder- Anemia akibat kanker (AAK)
• Anemia akibat pengobatan kanker (AAPK) (?)
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Anemia akibat pengobatan kankerAnemia akibat pengobatan kanker
• Kemoterapi sitostatika :
- Mielotoksik leukopenia, trombopenia, anemia
- Toksik ginjal cisplatin
- sintesis DNA dihambat semua sitostatika
• antimetabolik : anemia megaloblastik.
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Patogenesis Anemia Akibat Kanker (AAK)
1. Usia eritrosit memendek2. Respons sumsum tulang thd anemia menurun3. Transportasi besi dari sel RES ke sumsum
tulang menurun atau terhambat.4. Pengaruh sitokin terhadap sel RES dan
sumsum tulang.
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Usia eritrosit memendekUsia eritrosit memendek
• Sel RES hiperaktif menghancurkan eritrosit darah tepi dan sel eritroid muda sumsum tulang.
• Makrofag lebih aktif mengenyahkan eritrosit dari sirkulasi.
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Respon sumsum tulang thd Respon sumsum tulang thd anemia menurunanemia menurun
• Normal : Hb hipoksemia hipoksia ginjal produksi eritropoitin meningkat merangsang prekursor eritroid sumsum
tulang eritrosit Hb • ACD / AAK :
Hb kadar eritropoitin < respon eritropoietin menurun prekursor eritroid tidak sensitif sitokin inflamasi : IL-1 & IL-1 , TNF- , TGF menghambat produksi eritropoietin (89%)
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Transportasi besi dari RES ke sumsum tulang Transportasi besi dari RES ke sumsum tulang terhambatterhambat == ‘Reticuloendothelial Iron Block’‘Reticuloendothelial Iron Block’
• Besi di RES meningkat• Besi di sumsum tulang & darah tepi menurun• Penyebab :
- Normal• Apotransferin mengikat makrofag dlm RES besi dari eritrosit hancur• Diikat apotransferin ke sumsum tulang sintesis Hb.• Inflamasi kronik :- IL-1 , merangsang apolaktoferin yg berkompetisi dng apotransferin pd makrofag.- Apolaktoferin berikatan dng besi dlm RES laktoferin.- Laktoferin tdk dpt membawa besi ke sumsum tulang
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Besi dari RES ke sumsum tulang Terhambat Besi dari RES ke sumsum tulang Terhambat = ‘Reticuloendothelial Iron Block’ akibatnya := ‘Reticuloendothelial Iron Block’ akibatnya :
• Besi di RES meningkat• Besi di sumsum tulang & darah tepi menurun
• Inflamasi kronik :- IL-1 , merangsang apolaktoferin yg berkompetisi dng apotransferin pd makrofag.- Apolaktoferin berikatan dng besi dlm RES laktoferin.- Laktoferin tdk dpt membawa besi ke sumsum tulang
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Pengaruh Sitokin thd RES & Sumsum Pengaruh Sitokin thd RES & Sumsum tulang.tulang.
• TNF :- Diperantarai TNF (mediator), sintesis eritropoietin prekursor eritrosit Hb - Diperantarai mediator lain
• IL-1 : merangsang IFN- menekan eritropoiesis.
• IL-6• TGF-
Menekan eritropoiesis
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Pendekatan Diagnosis APPKPendekatan Diagnosis APPK
• Diagnosis AAK : Singkirkan lebih dulu anemia lain pada APPK
Cara : • Anamnesis • Pem. Fisik • Lab skrining
• Morfologi eritrosit • Retikulosit koreksi
Algoritma anemiaAnemiaHiperregeneratif
AnemiaHiporegeneratif :
Algoritma SpesifikLab khusus• Status besi• Status B12 • Asam folat• dll
• AAK (?) atau anemia akibat terapi kanker (?)
• APPK (?)
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Pendekatan Diagnosis APPKPendekatan Diagnosis APPK
• Diagnosis AAK : Singkirkan lebih dulu anemia lain pada APPK
• Cara : Anamnesis Pemeriksaan fisik Laboratorium skrining
• Morfologi eritrosit• Retikulosit koreksi
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Pendekatan Diagnosis APPKPendekatan Diagnosis APPK
• Diagnosis AAK : Singkirkan lebih dulu anemia lain pada APPK
ANEMIA :
Hiperregeneratif
Hiporegeneratif
Laborat khusus :• Status besi• Status B12 • Asam folat
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• Tujuan koreksi anemia pd pendrt kanker :- Meningkatkan kadar Hb :
• Terapi definitif (+)- Meningkatkan kualitas hidup (st lanjut)- Meningkatkan hasil pengobatan (st terlokalisir)
• Cara Koreksi Anemia- Transfusi darah : risiko infeksi & reaksi transfusi- Obat-obat anemia : khusus- Eritropoietin Rekombinan (?)- Anti TNF-
• Koreksi Anemia memperbaiki prognosis
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What is The Recommended What is The Recommended ManagementManagement
• There has been a PARADIGM SHIFT in the management of anemia from the physiological to the functional. Patients are living longer either reccurence-free or with their cancer.
• Intervention should not be delayed until a patient reaches physiological anemia, I.E, hemoglobin falls to 80 g/L (Hb 8 gr%)
• Intervention should be initiated when a patient has a major drop of hemoglobin > 1.5 g/L even if the hemoglobin is at level of 120 g/L
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Pengobatan Kanker dng Eritropoitin Pengobatan Kanker dng Eritropoitin (EPO)(EPO)
Alasan :- Anemia pd kanker termasuk ACD- Eritropoeitin relativ kurang pd ACD- Pengobatan anemia dgn eritropoietin pada reumatoid artritis/ HIV berhasil
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Eritropoietin (EPO)Eritropoietin (EPO)
• Endogen :- Hormon glikoprotein : ginjal >>>
Hati <<<- Humoral regulator produksi eritrosit yg utama- Kadar Hb tekanan O2 jaringan ginjal produksi EPO
• Eksogen- Rekombinan- Sel ovarium ‘chinese hamster’- Ditransfeksi dng gen EPO manusia
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Indikasi, Dosis, Lama terapi r-HuEPOIndikasi, Dosis, Lama terapi r-HuEPO
• Indikasi : Kanker
• Dosis & lama- 4 minggu (ke-1) : 3 x 10.000 I.u perminggu (300 iu/kg, 3x seminggu- Pada minggu (ke-4) : evaluasi respon terapi
• Respon (-) 300 iu/kg, 3x seminggu s/d minggu (ke-8)
• Respon (+) 16 minggu
• Parameter :- Kenaikan Ht & kebutuhan transfusi darah
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Anti TNF-Anti TNF-
• Menghambat efek sitokin (TNF-) yg mengganggu proses eritropoesis.
• Belum tersedia di Indonesia
• identik dgn pengobatan pada penderita kolitis ulseratif.
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Kesimpulan (1)Kesimpulan (1)
• Insiden anemia pada pasien kanker > 60%• Anemia pada pasien kanker merupakan
masalah• Anemia akibat kanker (AAK) tidak sama dgn
anemia pd pasien kanker (APPK)• Sebelum mengobati anemia akibat kanker
(AAK) singkirkan : APPK lainnya.• Koreksi anemia meningkatkan kualitas hidup
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Kesimpulan (2)Kesimpulan (2)
• Pemberian r-HuEPO pd penderita kanker memberikan respon terapi berupa kenaikan Ht dan penurunan kebutuhan transfusi darah secara signifikan.
• Respon pemberian r-HuEPO pada kanker stadium selanjutnya akan meningkatkan kualitas hidup
• Pemberian r-HuEPO pada kanker stadium terlokalisir akan meningkatkan hasil pengobatan.
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Bp. Jelangkung
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Auto Immune Hemolytic Anemia( AIHA )
Anemia Hemolitik Auto Immune( AHA )
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Adalah suatu Anemia Hemolitik karena destruksi Eritrosit yg mengikat dgn adanya auto antibodi terhadap eritrosit sendiri
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Eritrosit diselimuti antibodi (IgG) dgn atau tanpa komplemen
Terjadi kerusakan membran eritrosit
Eritrosit di fagositer di organ RES (Liver, Lien) terjadi Hemolisis ekstravaskuler
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Primer (Ididopathic) : Pnykt yg mendasari (-)
Etiologi
Sekunder : Pnykt yg mendasari (+)
Warm Reacting
Antibodi Cold Reacting
Mixed
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Classification of Autoimmune Hemolytic Anemia
I. On basis of serologic characteristics of involved autoimmune process :
a. Warm autoantibody type-autoantibody maximally active at body temperature 370 C
b. Cold autoantibody type-autoantibody active at temperature below 370 C.
c. Mixed cold and warm autoantibodies
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II. On basis of presence or absence of underlying or significantly associated disorder :
a. Primary or idiopathic AHAb. Secondary AHA :1. Associated with lymphoproliferative disorder2. Associated with the rheumatic disorder, particulary SLE3. Associated with certain infections4. Associated with certain nonlymphoid neoplasm, e.g ovarian
tumors5. Associated with certain chronic inflammatory diseases, e.g
ulcerative colitis6. Associated ingestion of certain drugs, e.g -methyldopa
Classification of Autoimmune Hemolytic Anemia
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Bisa terjadi pd semua umur Pada AIHA sekunder autoantibodi bisa
berasal dari ggn regulasi imunologik (SLE, Leukemia limfositik, MM)
Methyldopa pd individu tertentu akan menginduksi antibodi spesifik dgn mekanisme yg blm diketahui
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• Gejala2 Anemia
• Onset lambat, tapi bisa cepat
• Splenomegali
• Bisa tampil pertama kali pd kehamilan
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• Anemia Ringan s/d Berat ( krisis )• Sediaan Apus Darah Tepi (Peripheral Blood Film ) ada
polikromasi, sferosit, fragmentasi• Trombositopenia (Evan’s Syndrome)• BMA : Hiperplasia Eritrosit• Bilirubin Total , Indirek lebih dominant• LDH • ICT, DCT positif ( Indirect Comb’s Test, Direct Comb’s
Test )
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Wash Red Cell Transfusion
Prednison 1-2 mg/ KgBB/ hari/ oral
Methyl Prednisolone 300 mg/ hari/ iv
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