Aplastic Anemia

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Aplastic Anemia

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Aplastic Anemia

• Definition
• Pancytopenia with hypocellularity (Aplasia) of
  Bone Marrow
• One cell line may be affected more than the
  others
• Aplastic anemia is a severe, life threatening
  syndrome in which production of erythrocytes,
  WBCs, and platlets has failed.

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• Aplastic anemia may occur in all age groups and
  both genders.
• The disease is characterized by peripheral
  pancytopenia and accompanied by a hypocellular
  bone marrow.
• Failure of the bone marrow percursors to produce
  mature cells. Characterized by hypocellular
  marrow and pancytopenia.

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Etiology

• Acquired More common
• Inherited Fanconi anemia
• Acquired
• Drugs
• Agents with predictable, dose-related effects
  (e.g., chemotherapeutic drugs)
•  Agents with unpredictable, non-dose-related
  effects (e.g., chloramphenicol)
• - Cytotoxic drugs - Antibiotics
• - Chloramphenicol - Anti-inflammatory
• - Anti-convulsant - Sulphonamides
• - 2-3 months usually between exposure and the
  development of aplastic anemia.

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Aplastic Anemia (Cont.)

• Acquired
• Radiations
• Chemicals e.g., Benzene and pesticides
• Viruses
• Hepatitis A, Non-A and Non-B
• Herpes simplex
• E-B virus
• Parvovirus Transient
• Important clinically in patients with hemolytic
  anemias
• 5-10 of cases of AA in the West and 10-20 in
  the Far East.
• 2-3 months between exposure to the virus and the
  development of AA.
• Immune SLE, RA (rheumatoid arthritis)
• Pregnancy
• Idiopathic 75
• PNH

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INHERITED(20)

• Fanconi Anaemia
• Dyskeratosis congenita
• Shwachman-Diamond syndrome
• Diamond-Blackfan anaemia.

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• substantial reduction in the number of
  haemopoietic pluripotential stem cells, and a
  fault in the remaining stem cells or an immune
  reaction againstthem, which makes them unable to
  divide and differentiate sufficiently to populate
  the bone marrow.
• A primary fault in the marrow microenviromnent
  has also been suggested but the success of stem
  cell transplantation (SCT) shows this can only be
  a rare cause because normal donor stem cells are
  usually able to thrive in the recipient's marrow
  cavity.

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Pathogenesis

• Potential mechanisms
• Absent or defective stem cells (stem cell
  failure).
• Abnormal marrow micro-environment.
• Inhibition by an abnormal clone of hemopoietic
  cells.
• Abnormal regulatory cells or factors.
• Immune mediated suppression of hematopoiesis.
• It is believed that genetic factors play a role.
  There
• is a higher incidence with HLA (11) histo comp.
• Antigen. Immune mechanism is involved.

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Pathogenesis (Cont)

• The latest theory is
• there is an intrinsic derangement
• of hemopoietic proliferative capacity, which is
  consistent
• with life. The immune mechanism attempt to
  destroy
• the abnormal cells (self cure) and the clinical
  course and
• complications depend on the balance. If the
  immune
• mechanism is strong, there will be severe
  pancytopenia.
• If not, there will be myelodysplasia.

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• Forms of disease
• Inevitable dose related e.g. cytotoxic drugs,
  ionizing radiation. The timing, duration of
  aplasia and recovery depend on the dose. Recovery
  is usual except with whole body irradiation.
• Idiosyncratic unpredictable to drugs e.g.,
  anti-inflammatory antibiotics, anti-epileptic,
  these agents usually do not produce marrow
  failure in the majority of persons exposed to
  these agents.

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Clinical Features

• Non-specific
• Bruising, petechiae
• Manifestations of anemia
• Infections
• Hematological findings
• Peripheral blood
• Pancytopenia initially only 1 or 2 parameters.
  WBC lt 2.0, Hb lt 10. Plat. lt 100. No gross
  morphological abnormalities.
• Anemia is usually NCNC.
• Reticulocytopenia.
• 10 Hams test is (complement mediated lysis)

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Clinical Features

• Hematological findings (Cont)
• Bone Marrow
• Hypocellular
• lt50 of normal cellularity Trephine biopsy is
  the most important for diagnosis.
• Most of the cells present are lymphocytes, plasma
  cells and stromal cells.
• Iron stores increased

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BM Aspiration
BM Biopsy
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BM biopsyhypocellular ,increased fat spaces
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Treatment

• Withdrawal of etiological agents.
• Supportive.
• Restoration of marrow activity
• Bone marrow transplant
• Immunosuppressive treatment
• - Prednisolone - Antilymphocyte glob.
• - Cyclosporin - Anti T cells abs.
• - Splenectomy
• Androgens
• Growth factors

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Clinical Course

• Usually fatal in constitutional type.
• In the acquired type depends on severity
  defined by retic count, months or years depending
  on the severity.
• Stable course constant over a long period.
• Progressive, fluctuating.
• Unstable Associated with abnormal clones.

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Degree of Severity of Acquired Aplastic Anemia 
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Inherited Anemia

• Fanconis Anemia
• The most common type of inherited aplastic
  anemias.
• Associated with anomalies e.g., skeletal, skin.
• Autosomal recessive.
• Marrow failure is at the level of CFU-GM.
• Genetics
• Increased sensitivity of the cells to chromosomal
  damage by DNA cross linking agents.
• 5 genes are responsible A? E.
• IV54 mutation, is associated with multiple
  dysmorphism, severe pancytopenia, higher
  incidence of AML.

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Inherited Anemia

• Clinical Features
• Skeletal and skin anomalies seen at birth e.g.,
  microcephally.
• Manifestations of marrow failure, usually later
  at age 5-10 yrs. Present as anemia, mucusal
  bleeding e.g. nasal.
• Chromosomal breaks.

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Clinical Features of Fanconis Anemia

• Common Findings
• Low birth weight
• Short stature
• Microcephaly
• Microphthalmia
• Microstomia
• Skeletal abnormalities, particularly of thumbs
  and radii
• Hypoplastic hypothenar eminences
• Generalized increased pigmentation of skin

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Clinical Features of Fanconis Anemia

• Patches of hypopigmentation
• Cryptorchism
• Abnormalities of renal anatomy
• Horseshoe kidneys - Pelvic kidney
• Strabismus
• Hyper-reflexia
• Uncommon associations
• Mental retardation
• Vascular malformations
• Growth hormone deficiency

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PURE RED CELL APLASIA

• PURE RED CELL APLASIA
• Pure red cell aplasia is characterized by a
  selective decrease in erythroid precursor cells
  in the bone marrow. WBCs and platlets are
  unaffected.
•         Acquired
• Transitory with viral or bacterial infections
• Patients with hemolytic anemias may suddenly halt
  erythropoiesis
• Patients with thymoma  T-cell mediated responses
  against bone marrow erythroblasts or
  erythropoietin are sometimes produced.
•         Congenital
• Diamond-Blackfan syndrome occurs in young
  children and is progressive. It is probably due
  to an intrinsic or regulatory defect in the
  committed erythroid stem cell.