Aplastic Anemia

ETIOLOGY AND EPIDEMIOLOGY.

Drugs
Chemicals
Toxins
infectious agents
radiation
immune disorders

Mechanism - direct destruction of hematopoietic progenitors

destruction of the marrow and its necessary growth factors,
direct or indirect (e.g., virus-related) immune-mediated destruction of
marrow elements

careful history of exposure to known risk factors

genetic predisposition to bone marrow failure should always be considered
incidence of acquired aplastic anemia is low

drugs
antineoplastic agents (e.g., anthracyclines, alkylators, antimetabolites)
antibiotics (e.g., chloramphenicol).
Insecticides
Anticonvulsants
nonsteroidal anti-inflammatory agents
antihistamines
sedatives
metals).

viruses
Parvovirus B19 = pure red blood cell (RBC) aplasia,
sickle cell disease = transient aplastic crisis
hepatitis virus (both hepatitis B virus and hepatitis C virus
dengue virus
Herpes viruses
Epstein-Barr virus (EBV)
cytomegalovirus (CMV),
HIV

paroxysmal nocturnal hemoglobinuria (PNH)

collagen vascular diseases
bone marrow replacement by leukemic or neuroblastoma malignant cells.

PATHOLOGY AND PATHOGENESIS.

peripheral pancytopenia
hypoplastic or aplastic bone marrow.
two or more cell components have become seriously compromised
an absolute neutrophil count <500/mm3
a platelet count <20,000/mm3
a reticulocyte count <1% after correction for the hematocrit
bone marrow biopsy = hypocellular.

CLINICAL MANIFESTATIONS, LABORATORY FINDINGS, AND DIFFERENTIAL

DIAGNOSIS.

Acquired pancytopenia = anemia, leukopenia, and thrombocytopenia

The pancytopenia = fatigue, cardiac failure, infection, and bleeding

cancer, collagen vascular disorders, PNH, or infections that may respond to specific
therapies (e.g., intravenous immune globulin for parvovirus) should be considered in the
differential diagnosis.

peripheral blood smear for RBC, leukocyte, and platelet

congenital pancytopenia must always be considered and chromosomal breakage should
be evaluated (see earlier).
presence of fetal hemoglobin suggests a congenital pancytopenia

rule out PNH, a Ham's test should be performed.

Bone marrow examination should include both aspiration and a biopsy,
the marrow should be carefully evaluated for cellularity and morphology.
The presence of more than 70% lymphocytes has a poor prognosis.

COMPLICATIONS.

life-threatening bleeding due to thrombocytopenia

infection secondary to protracted neutropenia. =serious bacterial infections , invasive
mycoses.
TREATMENT.

supportive care
treat the underlying marrow failure.
antithymocyte globulin (ATG),
corticosteroids
cyclosporine
bone marrow transplantation
hematopoietic colony-stimulating factors
allogeneic bone marrow transplantation = complications of the transplantation, graft
versus host disease (which increases with patients' age), and the increased risk for
subsequent cancers
androgens, cyclophosphamide, and plasmapheresis.
PROGNOSIS.

severe pancytopenia have an extremely poor prognosis

PANCYTOPENIAS CAUSED BY MARROW REPLACEMENT

before or during malignancy = neuroblastoma or leukemia

consequence of osteoporosis -marble bone disease
myelofibrosis,
myelodysplasia.
collagen vascular disease (e.g., rheumatoid arthritis)
Chromosomal analysis = myelodysplastic syndromes .