3. Aplastic anemia
Aplastic anemia is a severe, life threatening syndrome in
which production of erythrocytes, WBCs, and platelets
has failed.
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.
5. Aplastic anemia
PATHOPHYSIOLOGY:
The primary defect is a reduction in or depletion
of hematopoietic precursor stem cells with
decreased production of all cell lines. This is what
leads to the peripheral pancytopenia.
6. This may be due to quantitative or qualitative damage
to the pluripotential stem cell.
In rare instances it is the result of
1. Abnormal hormonal stimulation of stem cell
proliferation or
2. The result of a defective bone marrow
microenvironment or
3. From cellular or humoral immunosuppression of
hematopoiesis.
8. Aplastic anemia
ACQUIRED
Most cases of aplastic anemia are idiopathic and
there is no history of exposure to substances known
to be causative agents of the disease
Exposure to ionizing radiation – hematopoietic
cells are especially susceptible to ionizing radiation.
Whole body radiation of 300-500 rads can
completely wipe out the bone marrow. With
sublethal doses, the bone marrow eventually
recovers.
Chemical agents – include chemical agents with a
benzene ring, chemotherapeutic agents, and certain
insecticides.
Idiosyncratic reactions to some commonly used
drugs such as chloramphenicol or quinacrine.
9. Aplastic anemia
Infections – viral and bacterial infections such as
infectious mononucleosis, infectious hepatitis,
cytomegalovirus infections, and miliary
tuberculosis occasionally lead to aplastic anemia
Pregnancy (rare)
Paroxysmal nocturnal hemoglobinuria – this is
a stem cell disease in which the membranes of
RBCs, WBCs and platlets have an abnormality
making them susceptible to complement mediated
lysis.
Other diseases – preleukemia and carcinoma
10. Aplastic anemia
CONGENITAL DISORDERS
Fanconi’s anemia – the disorder usually
becomes symptomatic ~ 5 years of age and is
associated with progressive bone marrow
hypoplasia. Congenital defects such as skin
hyperpigmentation and small stature are also seen
in affected individuals.
Familial aplastic anemia – a subset of Fanconi’s
anemia in which the congenital defects are absent.
13. Aplastic anemia
LAB FINDINGS
Severe pancytopenia with relative lymphocytosis
(lymphocytes live a long time)
Normochromic, normocytic RBCs (may be
slightly macrocytic)
Mild to moderate anisocytosis and poikilocytosis
Decreased reticulocyte count
Hypocellular bone marrow with > 70% yellow
marrow
14. TREATMENT
in untreated cases the prognosis is poor
Remove causative agent, if known
Multiple transfusions
Bone marrow transplant
15. Related disorders
Disorders in which there is peripheral
pancytopenia, but the bone marrow is
normocellular, hypercellular, or infiltrated with
abnormal cellular elements
Myelopthesic anemia – replacement of bone
marrow by fibrotic, granulomatous, or neoplastic
cells
16. Related disorders
MYELODYSPLASTIC SYNDROMES – are primary,
neoplastic stem cell disorders that tend to terminate in acute
leukemia.
The bone marrow is usually normocellular, or hypercellular
with evidence of qualitative abnormalities in one or more cell
lines resulting on ineffective erythropoiesis and/or
granulopoiesis and/or megakaryopoiesis.
The peripheral smear shows dysplastic (abnormality in
development) cells including nucleated RBCs, oval
macrocytes, pseudo-Pelger-Huet PMNs (hyposegmented
neutrophils) with hyperchromatin clumping, hypogranulated
neutrophils, and giant bizarre platlets.
HYPERSPLENISM – why can this lead to pancytopenia?
17. 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.
18. Pure Red Cell Aplasia
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.
19. OTHER HYPOPROLIFERATIVE
ANEMIAS
Renal disease – due to decreased erythropoietin
Endocrine deficiencies – may lead to decreased
erythropoietin production. For example:
hypothyroidism leads to decreased demand for
oxygen from tissues; decreased androgens in
males; decreased pituitary function