hematology aplasticanemia-120108092936-phpapp02
TRANSCRIPT
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Aplastic Anemia
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Dr. Kalpana MallaMD Pediatrics
Manipal Teaching Hospital
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PANCYTOPENIA:
• Simultaneous presence of anaemia, leukopenia, thrombocytopenia
• Causes: aplastic anemia Subleukemic leukemia cytotoxic drugs radiotherapy bone marrow infiltration hypersplenism megaloblastosis SLE
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APLASTIC ANEMIA:
• Failure of two or more cell lines• Anaemia, leukopenia,
thrombocytopenia + Hypoplasia or aplasia of the marrow
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Pathology:• Reduction in the amount of haemopoietic
tissue- inability to produce mature cells for discharge into the bloodstream
• Patchy areas of normo/hypercellularity betn areas of hypocellularity
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CLASSIFICATION:
• Idiopathic• Secondary: idiosyncratic drug reaction chemical exposure infectious hepatitis paroxysmal nocturnal haemoglobinuria• Constitutional
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CLASSIFICATION
CONSTITUTIONAL/CONGENITAL• Diamond-Blackfan syndrome• Shwachmann-Diamond syndrome• Fanconi anemia• Dyskeratosis Congenita• TAR (thrombocytopenia with absent radii)• Amegakaryocytic thrombocytopenia
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FANCONI ANEMIA
• Familial • AR• M:F=1.3:1• Onset in 1st decade of life• Diminished capacity for DNA repair and
increased random chromosome breakage during mitosis
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C/F:
• Facies – microphthalmia,depressed nasal bridge,epicanthic fold,micrognathia
• Hyperpigmentation, café-au-lait spots• Absent / hypoplastic thumb• Skeletal and renal lesions• Short stature, • Microcephaly , subnormal intelligence• Hypogonadism,ano malies of urinary tract• Predisposition to leukemias• Poor prognosis
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DYSKERATOSIS CONGENITA
• X-linked, AR, AD• M:F= 4.3:1• Hyperpigmentation• Nail dystrophy, early loss of teeth• Leukoplakia• Ocular abnormalities: cataract etc• Short stature but No skeletal/renal lesions (diff
from FA)
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DIAMOND BLACKFAN SYNDROME
• Congenital pure red cell aplasia• AD, AR, Sporadic• Familial in 15 %• 90 % diagnosed in 1st year of life• Intrinsic defect in RBC, early apoptosis• Macrocytic anemia, reticulocytopenia,
absence of RBC precursors in an otherwise normocellular bone marrow
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DIAMOND BLACKFAN SYNDROME
• Eye - Wide set eyes, blue sclera,glaucoma,epicanthic fold,cataract,strabismus
• Thick upper,cleft lip palate in some cases• lip,intelligent expression• Upperlimb anomalies – flattening of thenar
eminence, Triphalangeal thumb
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C/F:
• Profound anemia at 2-6 months of age• Short stature• Renal anomalies and hypogonadism maybe
present
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ACQUIRED APLASTIC ANEMIA - CAUSES
• Radiation• Drugs and chemicals - chemotherapy - benzene - chloramphenicol - antiepileptics• Viruses: - CMV - EBV - Hep B, C,D - HIV
• Immune diseases: - eosinophilic fascitis - thymoma • Pregnancy• PNH• Marrow replacement: - leukemia - myelofibrosis - myelodysplasia
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PATHOPHYSIOLOGY
• Direct destruction of haemopoietic progenitors
• Disruption of marrow micro-environment• Immune –mediated suppression of marrow
elements Cytotoxic T cells in blood and marrow
release gamma IFN and TNF -> inhibit early and late progenitor cells
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Pathology:
• Hallmark: peripheral pancytopenia with hypoplastic/ aplastic bone marrow
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CLINICAL FEATURESRBC (anemia)• Progressive and persistent pallor• Anemia related symptoms WBC (Leucopenia/neutropenia)• Prone to infections - Pyodermas, OM,
pneumonia, UTI, GI infections, sepsisPlatelets (Thrombocytopenia)• Petechiae, purpura, ecchymoses• Hematemesis, hematuria, epistaxis, gingival bleed• IC bleed- headache, irritability, drowsiness, coma
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NO HEPATOMEGALY
NO SPLENOMEGALY
NO LYMPHADENOPATHY
Failure of entire RES. No extramedullary hematopoesis
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Blood picture:
• Anemia-normocytic, normochromic • Leukopenia (neutropenia)• Relative lymphocytosis• Thrombocytopenia• Absolute reticulocyte count low• Mild to moderate anisopoikilocytosis
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Other investigations
• BM : dry aspirate, hypocellular with fat (>70% yellow marrow)
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SEVERITYSEVERE APLASTIC ANEMIA• Granulocyte count <500/cu.mm• Platelet count <20,000/cu.mm• Reticulocytes <1%• BM < 25% of hematopoeitic cells
VERY SEVERE/ EXTREME APLASTIC ANEMIA• Above + Granulocyte count <200/cu.mm
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DIFFERENTIAL DIAGNOSIS• ITP• LEUKEMIA• MYELOID METAPLASIA
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Management:
• Identification and elimination of underlying cause
• Supportive therapy:1. Red cell transfusion for anemia2. Prevention and treatment of haemorrhage3. Prevention and treatment of infection
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SUPPORTIVE CARE
• Prophylactic antibiotics• If infection: cephalosporins + aminoglycosides
+ metronidazole• Antifungals: amphotericin B, fluconazole (if
fever >10 days despite antibiotics)
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THERAPY
DEFINITIVE
• BONE MARROW TRANSPLANTATION• IMMUNOSUPPRESSION
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BONE MARROW TRANSPLANTATION
• Treatment of choice• HLA matched donor. Usually siblings• Long term survival rates: 60-70%• Donor stem cells > 4 X 108 cells/kg
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IMMUNOSUPPRESSION
• Antithymocyte globulin (ATG)• Antilymphocyte glubulin (ALG)• Cyclosporin• Intensive immunosupression :
cyclophosphamide• Corticosteroids
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ATG administration:
• IV administration of Ig preparations containing antibody to human thymocytes
• Improvement in haematological indices in one-half of subjects
• Anaphylaxis
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ATG AND ALG
• Dose : 40 mg/kg/day X 4 days• Hematologic response rate 45%• Survival rate 60%• Side effects: serum sickness
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ANDROGENS
• No longer have primary role• Increase erythopoietin producion• Stimulate erythroid stem cells• Increase Hb levels in normal males methyl testosterone, testesterone enanthate,
oxymetholone, danazolOral dose : 2-5mg/kg/day, IM dose: 1-2mg/kg/wkSide effects: cholestatic jaundice, masculinization
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Corticosteroids:
• High dose steroids combined with anabolic agents
• Uncertain benefits• Side-effects
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HAEMATOPOIETIC GROWTH FACTORS
• GM-CSF• G-CSF• IL-3• IL-1• IL-6
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Thank youDownload more documents and slide shows on The
Medical Post [ www.themedicalpost.net ]