Aplastic anemia

What is Pancytopenia

• a reduction in the blood count of all the

major cell lines – red cells, white cells and
platelets.

• it has several causes which can be broadly divided into

decreased bone marrow production or increased
peripheral destruction.
What are the causes of pancytopenia
decreased bone marrow function
• aplasia (reduction of haemopoietic stem cells)
• acute leukaemia, myelodysplasia, myeloma
• infiltration with lymphoma, solid tumours, tuberculosis
• megaloblastic anaemia
Cont. ……
increased peripheral destruction
• splenomegaly
 Aplastic anemia

• Aplastic (hypoplastic) anemia is defined as

pancytopenia resulting from hypoplasia of the
bone marrow.
• it is classified into primary (congenital or acquired) or
secondary.
Aplastic anemia
Causes of
Aplastic Anemia
Pathogenesis

• the underlying defect in all cases appears to be a

substantial reduction in the number of
haemopoietic pluripotential stem cells, and a
fault in the remaining stem cells or an
immune reaction against them, which makes
them unable to divide and differentiate sufficiently to
populate the bone marrow.
Congenital:
Fanconi anemia (FA)
• it autosomal recessive pattern of inheritance.
• often associated with growth retardation and
congenital defects of:
the skeleton (e.g. microcephaly, absent radii or
thumbs), of
 the renal tract (e.g. pelvic or horseshoe kidney) or
skin (areas of hyper‐ and hypopigmentation)and
sometimes there is learning disability.
Cont. …..
• the usual age of presentation of FA is 3–14 years,
approximately 10% of patients develop acute
myeloid leukemia.
 (a) X-rays showing absent thumbs
(b) left kidney abnormally placed in the pelvis
Dyskeratosis congenita (DC)

• rare
• sex‐linked disorder, with nail and skin atrophy and
a high risk of pulmonary fibrosis, cirrhosis,
osteoporosis and cancer
Idiopathic acquired aplastic anemia

• this is the most common type of aplastic anemia,

accounting for at least two‐thirds of acquired case.
• in most cases haemopoietic tissue is the target of an
autoimmune process.
Secondary causes
• Ionizing radiation: accidental exposure (radiotherapy,
radioactive isotopes, nuclear power stations)
• Chemicals: benzene, organophosphates and other
organic solvents, DDT and other pesticides,
organochlorines, recreational drugs (ecstasy)
• Viruses: viral hepatitis (non-A, non~B, non-C, non-G in
most cases), EBV
Cont….
• Drugs
that regularly cause marrow depression (e.g.
busulfan, cyclophosphamide, anthracyclines,
nitrosoureas)
that occasionally or rarely cause marrow depression
(e.g. chloramphenicol, sulphonamides, gold, anti-
inflammatory, antithyroid, psychotrophic,
anticonvulsant!antidepressant drugs)
Clinical features
• the onset is at any age with peak incidences around
10–25 and over 60 years.
• it can be insidious or acute with symptoms and signs
resulting from anemia, neutropenia or
thrombocytopenia.
• bruising, bleeding gums, epistaxes and
menorrhagia
Cont….
• infections, particularly of the mouth and throat,
are common and generalized infections are frequently
life threatening.
• the lymph nodes, liver and spleen are not enlarged.
Cont….

• A careful history and examination, e.g. for bone

deformities, are needed at all ages to exclude inherited
forms.
Laboratory findings

• in aplastic anemia, there must be at least two of the

following:
1. anemia (hemoglobin <10 mg/dL), this is
normochromic, normocytic or macrocytic (mean cell
volume (MCV) often 95–110 fL), the reticulocyte count
is usually extremely low in relation to the degree of
anemia.
2. Neutrophil count <1.5 × 109/L.
3. Platelet count <50 × 109/L.
Cont….

4. the bone marrow shows hypoplasia, with loss of

hemopoietic tissue and replacement by fat
which comprises over 75% of the marrow.
• Trephine biopsy may show patchy cellular areas in
a hypocellular background, the main cells present
are lymphocytes and plasma cells; megakaryocytes
in particular are severely reduced or absent.
Cont. ….

5. Cytogenetic and, more recently, molecular analysis is

performed to exclude inherited forms and
myelodysplasia.