Aplastic Anemia

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

Failure of two or more cell lines
Anaemia, leukopenia,
thrombocytopenia + Hypoplasia or
aplasia of the marrow
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

CLASSIFICATION:
Idiopathic
Secondary:
idiosyncratic drug reaction
chemical exposure
infectious hepatitis
paroxysmal nocturnal haemoglobinuria
Constitutional
CLASSIFICATION
CONSTITUTIONAL/CONGENITAL
Diamond-Blackfan syndrome
Shwachmann-Diamond syndrome
Fanconi anemia
Dyskeratosis Congenita
TAR (thrombocytopenia with absent radii)
Amegakaryocytic thrombocytopenia


FANCONI ANEMIA
Familial
AR
M:F=1.3:1
Onset in 1
st
decade of life
Diminished capacity for DNA repair and
increased random chromosome breakage
during mitosis

C/F:
Facies microphthalmia,depressed nasal
bridge,epicanthic fold,micrognathia
Hyperpigmentation, caf-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

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)

DIAMOND BLACKFAN SYNDROME
Congenital pure red cell aplasia
AD, AR, Sporadic
Familial in 15 %
90 % diagnosed in 1
st
year of life
Intrinsic defect in RBC, early apoptosis
Macrocytic anemia, reticulocytopenia,
absence of RBC precursors in an otherwise
normocellular bone marrow

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

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

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

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

Pathology:
Hallmark: peripheral pancytopenia with
hypoplastic/ aplastic bone marrow

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

NO HEPATOMEGALY

NO SPLENOMEGALY

NO LYMPHADENOPATHY
Failure of entire RES. No extramedullary
hematopoesis
Blood picture:
Anemia-normocytic, normochromic
Leukopenia (neutropenia)
Relative lymphocytosis
Thrombocytopenia
Absolute reticulocyte count low
Mild to moderate anisopoikilocytosis



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


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
DIFFERENTIAL DIAGNOSIS
ITP
LEUKEMIA
MYELOID METAPLASIA
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
SUPPORTIVE CARE

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

THERAPY
DEFINITIVE

BONE MARROW TRANSPLANTATION
IMMUNOSUPPRESSION

BONE MARROW TRANSPLANTATION
Treatment of choice
HLA matched donor. Usually siblings
Long term survival rates: 60-70%
Donor stem cells > 4 X 10
8
cells/kg
IMMUNOSUPPRESSION
Antithymocyte globulin (ATG)
Antilymphocyte glubulin (ALG)
Cyclosporin
Intensive immunosupression :
cyclophosphamide
Corticosteroids

ATG administration:
IV administration of Ig preparations containing
antibody to human thymocytes
Improvement in haematological indices in
one-half of subjects
Anaphylaxis
ATG AND ALG
Dose : 40 mg/kg/day X 4 days
Hematologic response rate 45%
Survival rate 60%
Side effects: serum sickness

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


Corticosteroids:
High dose steroids combined with anabolic
agents
Uncertain benefits
Side-effects
HAEMATOPOIETIC GROWTH FACTORS
GM-CSF
G-CSF
IL-3
IL-1
IL-6

Thank you
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Medical Post [ www.themedicalpost.net ]