DIAGNOSIS
The first case of AA was described clinically by Ehrlich in
1888 as a "rapidly fatal
severe case of anemia and leukopenia with associated fever,
ulcerated gums and menorrhagia
in young women"; upon autopsy there was no active marrow.
Various clinical definitions
have been applied through the intervening century, but the most
current definition of severe AA is
"marked pancytopenia with at least two of the following:
granulocytes less than 500/microliter,
platelets less than 20,000/microliter, anemia with corrected
reticulocyte count less than 1%, plus
markedly hypoplastic marrow depleted of hematopoietic cells."
Moderate AA is defined as having a
hypocellular bone marrow and cytopenia in at least two cell lines
not in the severe range.
Onset is insidious and the initial
complaint may be progressive fatigue and
weakness due to the anemia, followed in some cases by hemorrhage,
usually from the skin
and mucosal linings, due to thrombocytopenia. Although bleeding
is usually mild, retinal or
other CNS bleeds may occur as the presenting sign. Infection is
rare despite the severe
neutropenia.
Physical examination reveals pallor and
possibly bruising or petechiae, although these
are not as evident as would be expected with the degree of
thrombocytopenia. AA patients exhibit no
lymphadenopathy or splenomegaly. Fever may or may not be
present.
Peripheral blood shows pancytopenia;
presence of immature RBC/WBCs strongly argues
against AA. RBCs may be mildly macrocytic due to increased erythropoietic stress but
usually are normocytic and normochromic 
.
The absolute neutrophil
count (%segs + %bands x
total WBCs) is low or will progressively decrease and there are
70-90% circulating
lymphocytes. The corrected reticulocyte count is very low or
zero, indicating lack of
erythropoiesis. Bleeding time may be prolonged even with normal
coagulation parameters.
Patients have an increased serum iron and a normal transferrin,
resulting in an elevated
transferrin saturation. Plasma iron clearance is decreased due
to a reduction in erythropoiesis.
Bone marrow
aspirate may be dry 
but the biopsy
will show severe hypocellular or
aplastic marrow with fatty replacement. There have been cases in
which the initial marrow
biopsy exhibited hypercellularity, implying that more than one
biopsy may be necessary for
accurate diagnosis. A severe depression is noted in all
hematopoietic progenitor cells,
including myeloid, erythroid, pluripotent cell lines and
megakaryocytes.
Diagnosis is based on finding the classic triad of anemia,
neutropenia and
thrombocytopenia in both blood and bone marrow specimens. X rays
are needed to rule out
bone lesions or neoplastic infiltrates; MRI has been useful in
clearly defining hypoplastic
marrow. Since the diagnosis is one of exclusion, all other
causes of pancytopenia and other
lab findings must be ruled out before AA can be diagnosed.
CREATED: 6/24/94,
LAST MODIFIED: 4/24/96,
UT DPALM MEDIC, copyright 1994-96
.
The absolute neutrophil
count (%segs + %bands x
total WBCs) is low or will progressively decrease and there are
70-90% circulating
lymphocytes. The corrected reticulocyte count is very low or
zero, indicating lack of
erythropoiesis. Bleeding time may be prolonged even with normal
coagulation parameters.
Patients have an increased serum iron and a normal transferrin,
resulting in an elevated
transferrin saturation. Plasma iron clearance is decreased due
to a reduction in erythropoiesis.
but the biopsy
will show severe hypocellular or
aplastic marrow with fatty replacement. There have been cases in
which the initial marrow
biopsy exhibited hypercellularity, implying that more than one
biopsy may be necessary for
accurate diagnosis. A severe depression is noted in all
hematopoietic progenitor cells,
including myeloid, erythroid, pluripotent cell lines and
megakaryocytes.