Anemia Aplastik

Dr.Jalila Zamzam, Sp.A

 Gangguan hematopoisis ditandai : -penurunan produksi eritroid,mieloid, dan megakariosit dalam sumsum tulang Pansitopenia pada darah tepi - keganasan sistem hematopoitik (-) - kanker metastatik yg menekan sumsum tulang (-)

 Aplasia : eritropoitik granulopoitik megakariositik

Panmieloptisis = Anemia Aplastik

Diagnosis
The International Agranulocytosis and Aplastic Anemia Study (IAAAS) Aplastic anemia : Haemoglobin 10 g/dl atau Hematokrit 30 Thrombocytopenia, 50.000/mm3 Leucocytopenia, 3500/mm3 granulositopenia, 1,5 x 109/L

ETIOLOGI :
Herediter:
Fanconi anemia Dyskeratosis congenital Schwachman-Diamond syndrome Amegakaryocytic thrombocytopenia

Acquired:
Obat-obatan :kloramfenikol, antirematik,

antitiroid
Zat Kimia : Benzene, insektisida Infeksi : virus hepatitis,tb milier Penyakit sistem imun

*Transfusion associated Graft versus host disease * radioaktif : radiasi, sinar Rontgen 70% kasus anemia aplastik : idiopatik
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Patofisiologi
1.Kerusakan sel induk hematopoitik LTC-IC(Longterm Culture initiating cell), LTMC (Longterm MarrowCulture), jumlah sel induk CD34 menurun sampai 1-10% dari normal BMT berhasil pd 60-80%kasus 2.Proses imunologi yg menekan hematopoisis th/Imunosupresif dgn Siklosporin atau Metilprednisolon menyembuhkan 70% 3.Kerusakan mikro sumsum tulang banyak penelitian tidak mendukung
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Classification
A. Acquired aplastic anemia 1. Idiopathic 2. Associated with radiation, chemical, or drugs a. Ionazing radiation (accidental or therapeutic exposure) b. Antineoplastic drugs c. Drugs or chemical exposure
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3. Associated or following infections: a. Viruses: hepatitis C, EBV, CMV, parvovirus B19, HIV b. Miliary tuberculosis c. Chronic mucocutaneous candidiasis 4. Paroxismal Nocturnal Hemoglobinuria (PNH) 5. Systemic disease (e.g., pancreatic disease, Shwachman-Diamond syndrome)

6. Graft Versus Host Disease (GVHD) 7. Immunologic disorders (e.g., X-linked lymphoproliferative disease, Thymoma) 8. Pregnancy 9. Preleukemic syndrome

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B. Constitutional aplastic anemia 1. With congenital anomalies (Fanconi anemia) 2. Without congenital anomalies (delayed onset) 3. Delayed onset aplasia with congenital Dysceratosis 4. Constitutional congenital aplastic anemia (Tipe II)- congenital trombocytopenia with delayed onset pancytopenia without congenital anomalies

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Manifestasi Klinis
Petekie, Echymosis, purpura, epistaksis Anemia pucat, anoreksia,palpitasi, dyspnoe Followed by systemic manifestation or local infections with fever, sore throat Tidak ditemukan adanya pembesaran organ hepar dan limpa(tanpa hepato/splenomegali)
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Peripheral blood: Decreased Hb Normocytic Normochromic Leucophenia Relative lymphocitosis Prolonged B.T B.M.P : Decreased in hematopoietic activity Very rare megakariosit /(-) >> fatty cell >> R.E.S cell
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TINGKAT KEPARAHAN ANEMIA APLASTIK :

Menurut The Internatinal Agranulocytosis and Aplastic Anemia Study (IAAS) : 1. Mild / Moderate aplastic anemia (MAA) adanya penurunan jumlah sel darah dimana penurunan tidak seberat pada severe aplastic anemia (SAA) 2. Severe aplastic anemia (SAA) selularitas sum-sum tulang (produksi sel darah) kurang dari 25% dan diikuti sedikitnya dua gejala sebagai berikut : - Jumlah netropil : < 500 /mm3 - Jumlah platelet : < 20.000/mm3 - Jumlah retikulosit : < 20.000/mm3 3. Very severe aplastic anemia (VSAA) jumlah netropil : < 2.00/mm3
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Differential Diagnosis
I.T.P & A.T.P A.L.L Preleukemic state in acute leukemia Myelofibrosis Neoplasmic infiltration

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1. Removal the causative agent 2. Therapeutic approaches: a. Supportive care Blood transfusion, antibiotics b. Androgen dan glucocorticosteroid therapy 1. Fluoxymesterone,orally, 0,4-1mg/kg daily 2. Methyltestosteron, or testosteron propionate, 1-2 mg/kg, usually 30 to 50 mg daily in divided dose 3. Testosteron enanthate, IM, 4 mg/kg once weekly or 9 mg/kg every 2 weeks
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Treatment

4. Testosteron cypionate, IM, 4 mg/kg once weekly or 8 mg/kg every 2 weeks 5. Oxymetholone, orally, 2 to 6,5mg/kg daily, max 100 mg daily 6. Nadrolone Decanoate,IM, 25 to 50mg every 3 to 4 weekss 3.Imunosuppresive therapy AntiThymociteGlobulin and dosis tinggi Cyclophosphamide sebelum bone marrow transplantation baik 4.Bone marrow transplantation HLA-matched HLA-identical sibling shows the best result
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5. Hematopoietic Growth Factors

G-CSF, GM-CSF dan IL-3 :

dapat meningkatkan jumlah granulosit

dapat diberikan pada pasien yang menderita

infeksi berat setelah terapi immunosuppresi

atau BMT

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PROGNOSIS :
Prognosis bergantung pada :

1. Gambaran sum sum tulang hiposeluler atau aseluler

2. Kadar Hb F yang lebih dari 200 mg% memperlihatkan prognosis yang lebih baik

3. Jumlah granulosit lebih dari 2000/mm3 menunjukkan

prognosis yang lebih baik 4.Pencegahan infeksi sekunder

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Sebab kematian
Infeksi : bronkopneumonia atau sepsis Perdarahan otak atau abdomen

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