3. Discuss the components and causes of bone marrow aplasia.

The aplastic anemias are characterized by peripheral blood pancytopenia, bone marrow
hypocellularity, and absence of a clonal hematological process. They have an incidence of
approximately two patients per million population in the West and four per million in Asia.
Bone marrow smears of various forms of aplasia:
a. Bone marrow cytology in erythroblastopenia: only activated cells of the granulopoietic
series are present. The megakaryopoiesis (not shown here) show no abnormalities (Theml,
Color Atlas of Hematology 2004 Thieme).

b Bone marrow aplasia: hematopoiesis is completely absent: only adipocytes and stroma
cells are seen (Theml, Color Atlas of Hematology 2004 Thieme).

c Giant erythroblast (arrow) in the bone marrow in acute parvovirus B19 infection (Theml,
Color Atlas of Hematology 2004 Thieme).

d Conspicuous binuclear erythroblasts in the bone marrow of a patient with congenital

dyserythropoietic anemia (type II CDA) (Theml, Color Atlas of Hematology 2004 Thieme).

Figure 1. Normal Bone Marrow, histological section (MODERN HEMATOLOGY Biology and
Clinical Management, Second Edition 2007 Humana Press Inc.)

Figure 2. Aplastic Anemia, histologic section ((MODERN HEMATOLOGY Biology and Clinical
Management, Second Edition 2007 Humana Press Inc.)
Morphology/Components (MODERN HEMATOLOGY Biology and Clinical Management,
Second Edition 2007 Humana Press Inc.; Robbins):
Contains acellular or hypocellular spicules (spicules: small needle-shaped bodies).
Cellular elements:
o May include a minimal number of residual myeloid or erythroid cells.
o Plasma cells and lymphocytes may be relatively increased in numbers but
they do not represent clonal populations.
o Fat cells and fibrous stroma
Major Causes of Aplastic Anemia (Stedmans, MODERN HEMATOLOGY Biology and Clinical
Management, Second Edition 2007 Humana Press Inc.)
INHERITED
Fanconi anemia - a type of idiopathic refractory anemia characterized by
pancytopenia, hypoplasia of the bone marrow, and congenital anomalies, occurring in
members of the same family (an autosomal recessive trait in at least five nonallelic types);
the anemia is normocytic or slightly macrocytic, macrocytes and target cells may be found
in the circulating blood, and the leukopenia usually is due to neutropenia. Congenital
anomalies include short stature; microcephaly; hypogenitalism; strabismus; anomalies of the
thumbs, radii, kidneys, and urinary tract; mental retardation; and microphthalmia
Diamond-Blackfan anemia - congenital nonregenerative, familial hypoplastic, or pure
red blood cell anemia; erythrogenesis imperfecta; Diamond-Blackfan syndrome; anemia
resulting from congenital hypoplasia of the bone marrow, which is grossly deficient in

erythroid precursors whereas other elements are normal; anemia is progressive and severe,
but leukocyte and platelet counts are normal or slightly reduced; survival of transfused
erythrocytes is normal.
Dyskeratosis congenital - premature keratinization in individual epithelial cells that
have not reached the keratinizing surface layer; dyskeratotic cells generally become
rounded, and they may break away from adjacent cells and fall off; epidermalization of the
conjunctival and corneal epithelium.
Kostmanns syndrome
Shwachman-Diamond syndrome
Thrombocytopenia absent radius syndrome- Congenital absence of the radius
associated with thrombocytopenia that is symptomatic in infancy but later improves;
congenital heart disease and renal anomalies occur in some cases; autosomal recessive
inheritance.
ACQUIRED
Idiopathic majority of cause
Chloramphenicol - can cause either dose-dependent bone marrow suppression
or idiosyncratic aplastic anemia
NSAIDS - indomethacin, diclofenac, and phenylbutazone
Sulfonamides/Sulfonylureas - Sulfa derivatives including the sulfa antibiotics,
the sulfonylureas, and furosemide all have been associated with aplastic anemia.
Antithyroid drugs
Anticonvulsants - the antiseizure medication carbamazepine also has been
implicated
Gold salts/Penicillamine - used to treat rheumatoid arthritis
Allopurinol - preferred and standard-of-care therapy for gout, which reduces
total uric acid body burden by inhibiting xanthine oxidase
Hepatitis - approximately 25% of patients with aplastic anemia have a history
of hepatitis occurring within several months prior to the development of pancytopenia.
Typically, the hepatitis is resolving when patients present with abnormal blood counts.
However, none of the hepatitis viruses identified so far, including hepatitis A, B, C, E, or G
(GVB-C), have been shown to be causally associated with the development of aplastic
anemia.
Benzene - causes dose dependent bone marrow failure
Ionizing radiation (Accidental Exposure) - rare cause of aplastic anemia;
approximately 100200 cGy of total body irradiation given as a single dose can cause
pancytopenia, whereas 400800 cGy can induce irreversible bone marrow failure.
Ionizing and Cytotoxic chemotherapy - iatrogenic causes of bone marrow
failure.