1. Aplastic Anemia
Dr. Kalpana Malla
MD Pediatrics
Manipal Teaching Hospital
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2. PANCYTOPENIA:
• Simultaneous presence of
anaemia, leukopenia, thrombocytopenia
• Causes: aplastic anemia
Subleukemic leukemia
cytotoxic drugs
radiotherapy
bone marrow infiltration
hypersplenism
megaloblastosis
SLE

3. APLASTIC ANEMIA:
• Failure of two or more cell lines
• Anaemia, leukopenia, thrombocytop
enia + Hypoplasia or aplasia of the
marrow

4. 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

5. CLASSIFICATION:
• Idiopathic
• Secondary:
idiosyncratic drug reaction
chemical exposure
infectious hepatitis
paroxysmal nocturnal haemoglobinuria
• Constitutional

6. CLASSIFICATION
CONSTITUTIONAL/CONGENITAL
• Diamond-Blackfan syndrome
• Shwachmann-Diamond syndrome
• Fanconi anemia
• Dyskeratosis Congenita
• TAR (thrombocytopenia with absent radii)
• Amegakaryocytic thrombocytopenia

7. 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

8. 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

9. 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)

10. 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

11. 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

12. C/F:
• Profound anemia at 2-6 months of age
• Short stature
• Renal anomalies and hypogonadism maybe
present

13. ACQUIRED APLASTIC ANEMIA -
CAUSES
• Radiation • Immune diseases:
• Drugs and chemicals - eosinophilic fascitis
- chemotherapy - thymoma
- benzene • Pregnancy
- chloramphenicol • PNH
- antiepileptics • Marrow replacement:
• Viruses: - leukemia
- CMV - myelofibrosis
- EBV - myelodysplasia
- Hep B, C,D
- HIV

14. 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

15. Pathology:
• Hallmark: peripheral pancytopenia with
hypoplastic/ aplastic bone marrow

16. CLINICAL FEATURES
RBC (anemia)
• Progressive and persistent pallor
• Anemia related symptoms
WBC (Leucopenia/neutropenia)
• Prone to infections -
Pyodermas, OM, pneumonia, UTI, GI
infections, sepsis
Platelets (Thrombocytopenia)
• Petechiae, purpura, ecchymoses
• Hematemesis, hematuria, epistaxis, gingival bleed
• IC bleed- headache, irritability, drowsiness, coma

17. NO HEPATOMEGALY
NO SPLENOMEGALY
NO LYMPHADENOPATHY
Failure of entire RES. No extramedullary
hematopoesis

18. Blood picture:
• Anemia-normocytic, normochromic
• Leukopenia (neutropenia)
• Relative lymphocytosis
• Thrombocytopenia
• Absolute reticulocyte count low
• Mild to moderate anisopoikilocytosis

19. Other investigations
• BM : dry aspirate, hypocellular with fat (>70%
yellow marrow)

20. SEVERITY
SEVERE 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

21. DIFFERENTIAL DIAGNOSIS
• ITP
• LEUKEMIA
• MYELOID METAPLASIA

22. Management:
• Identification and elimination of underlying
cause
• Supportive therapy:
1. Red cell transfusion for anemia
2. Prevention and treatment of haemorrhage
3. Prevention and treatment of infection

23. SUPPORTIVE CARE
• Prophylactic antibiotics
• If infection: cephalosporins + aminoglycosides
+ metronidazole
• Antifungals: amphotericin B, fluconazole (if
fever >10 days despite antibiotics)

24. THERAPY
DEFINITIVE
• BONE MARROW TRANSPLANTATION
• IMMUNOSUPPRESSION

25. 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

26. IMMUNOSUPPRESSION
• Antithymocyte globulin (ATG)
• Antilymphocyte glubulin (ALG)
• Cyclosporin
• Intensive immunosupression :
cyclophosphamide
• Corticosteroids

27. ATG administration:
• IV administration of Ig preparations containing
antibody to human thymocytes
• Improvement in haematological indices in
one-half of subjects
• Anaphylaxis

28. ATG AND ALG
• Dose : 40 mg/kg/day X 4 days
• Hematologic response rate 45%
• Survival rate 60%
• Side effects: serum sickness

29. ANDROGENS
• No longer have primary role
• Increase erythopoietin producion
• Stimulate erythroid stem cells
• Increase Hb levels in normal males
 methyl testosterone, testesterone
enanthate, oxymetholone, danazol
Oral dose : 2-5mg/kg/day, IM dose: 1-2mg/kg/wk
Side effects: cholestatic jaundice, masculinization

30. Corticosteroids:
• High dose steroids combined with anabolic
agents
• Uncertain benefits
• Side-effects

31. HAEMATOPOIETIC GROWTH FACTORS
• GM-CSF
• G-CSF
• IL-3
• IL-1
• IL-6

32. Thank you
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Medical Post [ www.themedicalpost.net ]