Lab Studies:

The first step in the diagnosis of anemia is detection with reliable accurate
tests so that important clues to underlying disease are not overlooked and
patients are not subjected to unnecessary tests for and treatment of
nonexistent anemia. Detection of anemia involves the adoption of arbitrary
criteria.
o The World Health Organiation!s criterion for anemia in adults is Hb
values less than "#.$ g%d&. 'hildren aged ( months to ( years are
considered anemic at Hb levels less than "" g%d&) and children
aged (*"+ years are considered anemic when Hb levels are less
than "# g%d&. The disadvantage of such arbitrary criteria is that a
few healthy individuals fall below the reference range) and some
people with an underlying disorder fall within the reference range
for Hb concentration.
o ,sually) ,- values are slightly higher. .nemia is suggested in
males with Hb levels less than "/.$ g%d& and in females with Hb
levels less than "#.$ g%d&. Higher values are anticipated in
individuals living in altitudes significantly above sea level.
'onditions with an increase in plasma volume) such as during the
last trimester of pregnancy) are associated with lower values
without an existent anemia because the red cell mass is normal.
Once the existence of anemia is established) investigate the
pathogenesis. 0f an ade1uate history has been taken and a physical
examination has been performed) the etiology may be obvious) and
confirmatory studies and appropriate therapy can be undertaken with a
minimum of investigation. 0f this is not the case) initiate a definite plan of
investigation considering the cost to the patient along with a determination
of the etiology of the abnormality.
. rational approach is to begin by examining the peripheral smear and
laboratory values obtained on the blood count. 0f the anemia is either
microcytic 2mean corpuscular volume 34'56) 78+9 or macrocytic 24'5)
:;(9 or if certain abnormal <='s or W='s are observed in the blood
smear) the investigative approach can be limited 2see Table ") Table #)
and Table /9.
>resently) <=' cellular indices are computer calculated and automatically
placed on laboratory reports. The formulae for calculating these values
follow 2reference ranges are in parentheses9. <=' is per million cells.
o 4'5 ? Hct @ "A%<=' 28+*;( f&9
o 4ean corpuscular Hb 24'H9 ? Hb @ "A%<=' 2#(*/( pg9
o 4ean corpuscular Hb concentration 24'H'9 ? Hb @ "A%Hct 2/#*
/(B9
. rapid method of determining whether cellular indices are normocytic and
normochromic is to multiply the <=' and Hb by /. The <=' multiplied by
/ should e1ual the Hb) and the Hb multiplied by / should e1ual the Hct.
Deviation from the calculated values suggests microcytosis) macrocytosis)
or hypochromia versus the presence of spherocytes 24'H') :/(9.
Table ". 4icrocytic Hypochromic .nemia 24'5) 78/C 4'H') 7/"9
Serum
Iron
Total
Iron-
Binding
Capacity
(TIBC)
Bone
Marrow
Iron
Comment
0ron
deficiency
A <esponsive to
iron therapy
'hronic
inflammation
DD ,nresponsive to
iron therapy
Thalassemia
major
E DDDD <eticulocytosis
and indirect
bilirubinemia
Thalassemia
minor
E E DD Flevation of . of
fetal
hemoglobin)
target cells) and
poikilocytosis
&ead
poisoning
E E DD =asophilic
stippling of
<='s
-ideroblastic E DDDD <ing
sideroblasts in
marrow
Hemoglobin E E DD Hemoglobin
electrophoresis
? increased) ? decreased) E ? normal) A ? absent) D!s indicate amount
of stainable iron in bone marrow specimens on a scale of A*+.
Table #. 4acrocytic .nemia 24'5) :;$9
4egaloblastic bone marrow Deficiency of vitamin =*"#
Deficiency of folic acid
Drugs affecting DE. synthesis
0nherited disorders of DE.
synthesis
Eonmegaloblastic bone
marrow
&iver disease
Hypothyroidism and
hypopituitarism
.ccelerated erythropoiesis
2reticulocytes9
Hypoplastic and aplastic anemia
0nfiltrated bone marrow
Table /. 5arious Gorms of <='s
4acrocyte &arger than normal 2:8.$ m diameter9. -ee
Table #.
4icrocyte -maller than normal 27H m diameter9. -ee
Table ".
Hypochromic &ess hemoglobin in cell. Fnlarged area of
central pallor. -ee Table ".
-pherocyte &oss of central pallor) stains more densely) often
microcytic. Hereditary spherocytosis and certain
ac1uired hemolytic anemias.
Target cell Hypochromic with central ItargetI of
hemoglobin. &iver disease) thalassemia)
hemoglobin D) postsplenectomy.
&eptocyte Hypochromic cell with a normal diameter and
decreased 4'5. Thalassemia.
Flliptocyte Oval to cigar shaped. Hereditary elliptocytosis)
certain anemias 2particularly vitamin =*"# and
folate deficiency9.
-chistocyte Gragmented helmet* or triangular*shaped
<='s. 4icroangiopathic anemia) artificial heart
values) uremia) malignant hypertension.
-tomatocyte -litlike area of central pallor in erythrocyte. &iver
disease) acute alcoholism) malignancies)
hereditary stomatocytosis) and artifact.
Tear*shaped
<='s
Drop*shaped erythrocyte) often microcytic.
4yelofibrosis and infiltration of marrow with
tumor. Thalassemia.
.canthocyte Give to "A spicules of various lengths and at
irregular interval on surface of <='s.
Fchinocyte Fvenly distributed spicules on surface of <='s)
usually "A*/A. ,remia) peptic ulcer) gastric
carcinoma) pyruvic kinase deficiency)
preparative artifact.
-ickle cell Flongated cell with pointed ends. Hemoglobin -
and certain types of hemoglobin ' and l.
0n microcytic hypochromic anemia) seek a source of bleeding. The
appropriate laboratory tests are serum iron level and T0=' and either
serum ferritin level or stain of bone marrow specimen for iron. 0f the serum
iron level is decreased and T0=' is increased) a diagnosis of iron
deficiency can be made) therapy can be initiated) and a search for the
cause of the iron deficiency can be started. 0f this cannot be
demonstrated) suspect each of the other causes of a microcytic anemia
listed in Table ") and the order of investigation can be influenced by
findings in the history) physical examination) or peripheral smear.
-imilarly) a reasonable approach with macrocytic anemia is to determine if
the bone marrow aspirate is megaloblastic. 0f so) attempt to incriminate
either vitamin =*"# or folic acid deficiency with appropriate laboratory
studies. -imilar to the establishment of a diagnosis of iron deficiency
anemia) a diagnosis of vitamin =*"# or folic acid deficiency does not stop
with an abnormal laboratory value for one of these vitamins. >rompt
treatment can be instituted) but a continued search for an underlying
cause of the vitamin deficiency is indicated 2see >ernicious .nemia9.
When a normocytic normochromic anemia is encountered) classify the
anemia into / possible etiologies 2ie) blood loss) hemolysis) decreased
production9. 0n most anemias) one of these causes is the dominant factor.
However) in certain anemias) more than a single cause may play an
important role. Gor example) pernicious anemia is predominantly due to
decreased production of erythrocytes) but hemolysis adds significantly to
the severity of anemia.
=lood loss
o Obviously) significant hemorrhage produces anemia. 0mmediately
after blood loss) the Hct cannot be used as a reliable method to
determine the 1uantity of lost blood because the patient loses
plasma as well as <='s. .fter acute hemorrhage) the Hct falls for
#+*+8 hours until the plasma volume is replaced. .t that time)
anemia is normochromic and normocytic with normal cellular
indices because the cells in the peripheral blood have been
produced prior to bleeding 2see 0ron Deficiency .nemia9.
o 0f the patient had ade1uate iron stores) accelerated production of
<='s occurs) so that " week after bleeding) a larger than normal
number of young <='s and reticulocytes are circulating in the
peripheral blood. =ecause reticulocytes and young <='s have a
larger volume 24'5 of approximately "#A9) macrocytes may be
observed in the peripheral smear) and a slight increase in the 4'5
occurs.
o 0f hemorrhage was sufficient to deplete iron stores 2"*# & of blood)
$AA*"AAA mg of iron9) newly formed erythrocytes are microcytic and
hypochromic and gradually replace normal erythrocytes in the
circulation that were produced prior to the induction of iron
deficiency. =ecause <='s normally survive for "#A days in
circulation) maximal changes in the 4'5 and 4'H' are not
observed until that time. 0ron deficiency and the depletion of iron
stores can be detected several weeks after bleeding by
measurements of the serum iron level and T0=' and%or special
stains of bone marrow specimens showing an absence of storage
iron.
o Diagnosis of iron deficiency anemia in an adult in the ,nited -tates
should be attributed to bleeding unless other causes can be
proven. .side from recent multiparity) other causes are relatively
uncommon and include prolonged dietary idiosyncrasies 2eg) clay
eating) laundry starch consumption) protein deprivation for several
years9) urinary loss of iron due to intravascular hemolysis 2eg)
artificial aortic valves) paroxysmal nocturnal hemoglobinuria9)
gastrectomy) and other upper gastrointestinal surgery or disease.
o Diagnosis of iron deficiency anemia is made by demonstrating that
the patient has low serum iron levels and elevated T0=') absence
of stainable iron in a bone marrow specimen) or both. . low serum
ferritin level provides confirmation of the diagnosis. The presence of
microcytosis and hypochromia is helpful but not diagnostic.
o 4icrocytic hypochromic anemia is observed with conditions other
than iron deficiency anemia. 'ertain types of these disorders are
iron*overloading states in which the administration of iron can be
deleterious to the patient 2see Table "9. -imilarly) low serum iron
levels can be observed in chronic inflammatory states with normal
body stores of iron. However) in the latter) the T0=' is usually
decreased rather than increased) and stainable iron can be
demonstrated in bone marrow aspirates. Whenever the diagnosis
of iron deficiency anemia is in doubt) follow*up blood work after
administration of iron to show correction of the anemia can be
helpful in confirming the diagnosis.
o The patient notices hemorrhage from most body organs. Fpistaxis)
hemoptysis) or hematuria of sufficient degree to cause anemia is
usually reported to the physician long before iron deficiency
ensues. However) bleeding from either the uterus or the
gastrointestinal tract may be disregarded by the patient or be totally
undetected until anemia becomes profound and symptomatic.
o 4enstrual bleeding among healthy females varies monthly from "A*
#$A m&. ,nless the patient observes a change in menses) she
relates that menses are normal unless specific 1uestions are
asked. The presence of clots) abdominal cramps) excessive
gushing of blood upon removal of tampons) the need for both
tampons and pads) and the use of an unusual number of pads or
tampons can be used to determine if menstrual bleeding may be
sufficient to induce iron deficiency anemia.
o Jastrointestinal bleeding is the other occult cause of anemia due to
blood loss. 0f hemorrhage is profuse) it is usually detected before
evidence of iron deficiency anemia occurs because hematocheia
or melena causes the patient to seek medical attention. However) if
the bleeding occurs slowly) it is usually undetected until anemia
ensues because stools appear normal.
o Fvery patient with iron deficiency anemia should have a stool
examination for occult blood. . positive result necessitates a careful
search of the gastrointestinal tract to identify the site of bleeding.
,nfortunately) a negative result does not exclude gastrointestinal
blood loss because bleeding can be intermittent and re1uire several
examinations for detection. .lso) less than #A*/A m& of blood in the
stool per day may go undetected due to the insensitivity of the test.
The # methods used to detect small daily losses of blood from the
gut are as followsK 2"9 placing the patient on a meat*free diet for
several days and using more sensitive methods) such as a
benidine test) and 2#9 labeling the patient!s <='s with chromium
$" and collecting stool specimens for the detection of the
radioisotope.
o 0nvestigate gastrointestinal bleeding by endoscopy and
radiographic studies 2see >rocedures9.
Hemolysis 2increased <=' destruction9
o . normal <=' survives in the circulation for "#A days. 0f the
erythrocytic lifespan is shortened significantly 27+A d9) the patient
has a hemolytic disorder that may be demonstrated by showing
increased production of erythrocytes) increased destruction) or
both. The former is revealed most readily by the presence of
sustained reticulocytosis and the latter by the occurrence of indirect
bilirubinemia 2see Table +9.
o Other laboratory tests are available to detect hemolysis) but they
are either more expensive or less reliable.
Table +. 'lassification of the Hemolytic Disorders
Hereditary c!uired
0ntracorpus
cular defect
Hereditary spherocytosis
Hereditary elliptocytosis
Hemoglobinopathies
Thalassemias
'ongenital
dyserythropoietic anemias
Hereditary <=' enymatic
deficiencies
<arer hereditary
abnormalities
5itamin =*"# and folic
acid deficiency
>aroxysmal nocturnal
Hemoglobinuria
-evere iron deficiency
Fxtracorpus
cular defect
Physical agents: Burns, cold
exposure
Traumatic: Prosthetic heart
valves, march
hemoglobinemia, DIC, graft
rejection
Chemicals: Drugs and
venoms
Infectious agents: alaria,
toxoplasmosis,
mononucleosis, hepatitis,
primary atypical
pneumonia, clostridial
infections, bartonellosis,
leishmaniasis
!epatic and renal disease
Collagen vascular disease
alignancies: Particularly
hematologic neoplasia
Transfusion of incompatible
blood
!emolytic disease of the
ne"born
Cold hemagglutinin
disease
#utoimmune hemolytic
anemia Thrombotic
thrombocytopenic purpura
$TTP% and hemolytic uremic
syndrome $!&'%
o .nemia solely due to hemolysis does not occur until <='s are
being destroyed at (*8 times the normal rate) reducing the mean
<=' lifespan to less than #A days because of the bone marrow!s
capacity to undergo (*fold hypertrophy and hyperplasia. Thus) if the
clinician relies on the presence of anemia to detect hemolytic
states) the clinician misses most of them and) perhaps) an
important clue to an underlying disorder. On the contrary) if
reticulocytosis and indirect bilirubinemia are used to detect
hemolytic states) they are usually found when the mean lifespan is
less than +A*$A days. 4ore sophisticated methods) such as
measurements of <=' lifespan) are re1uired to detect less severe
shortening of erythrocyte lifespan 2$A*"AA d9 and are only
occasionally needed in clinical practice.
o .ll patients with both reticulocytosis and indirect bilirubinemia have
a hemolytic disorder. .ll patients with sustained reticulocytosis have
a hemolytic disorder. ,nfortunately) the contrary is not the case)
and significant hemolysis can occur without reticulocytosis if the
bone marrow is unable to produce cells at an accelerated rate 2eg)
pernicious anemia) leukemia) aplasia9. . single demonstration of an
elevated reticulocyte count is insufficient to establish a diagnosis of
hemolysis because transient reticulocytosis may occur without
hemolysis 2eg) in the treatment of iron deficiency anemia9.
o .lmost all patients with indirect bilirubinemia have a hemolytic
disorder. 0n adults) the exception is patients with Jilbert disease.
These patients can be distinguished from those with hemolytic
disorders and those who have no other obvious stigmata of
hemolysis 2eg) anemia) reticulocytosis) 'oombs test9 by having the
patient fast for / days. 0n Jilbert disease) indirect bilirubin doubles
with starvation) whereas in hemolytic disorders) it does not. Once
the presence of hemolysis has been established) the etiology of the
increased rate of <=' destruction can be sought.
o .ll causes of hemolytic disorders are either hereditary or ac1uired.
-imilarly) they are due to either an intrinsic abnormality of the <='
2intracorpuscular defect9 or external factors that shorten the
erythrocyte lifespan 2extracorpuscular9. ,sing this nomenclature)
only + groups of hemolytic disorders are possibleLhereditary
intracorpuscular) hereditary extracorpuscular) ac1uired
intracorpuscular) and ac1uired extracorpuscular.
o .ll hereditary hemolytic disorders are due to intracorpuscular
defects) and most ac1uired disorders are due to extracorpuscular
abnormalities 2see Table +9. Hereditary etiologies of hemolytic
disease are suggested strongly in any patient with a family history
of anemia) jaundice) cholelithiasis) or splenectomy. Whenever
possible) family members) particularly parents) siblings) and
children) should undergo a hematologic examination) including
hemogram with reticulocyte count) indirect bilirubin determination)
and careful examination of the peripheral smear.
o 0f a specific hereditary hemolytic disorder 2eg) hereditary
spherocytosis) hemoglobinopathy9 is suggested in a patient)
examine blood from family members for that entity by appropriate
laboratory methods. Fstablishment of a hemolytic defect in other
closely related family members permits a presumptive diagnosis of
hereditary intracorpuscular hemolytic disorder in the patient.
-howing a similar <=' abnormality 2eg) spherocytes) abnormal Hb)
J*(*>D deficiency9 among family members establishes the basic
etiology. Once the probability of a hereditary hemolytic disorder is
established) a planned approach to determine the definitive
abnormality is usually simple.
o . careful examination of the peripheral smear may reveal
spherocytes in hereditary spherocytosisC ovalocytes in hereditary
elliptocytosisC sickle cells in patients with major hemoglobinopathies
associated with sickle HbC target cells in patients with Hb ' or F
diseaseC and marked poikilocytosis with target cells) microcytes)
and hypochromic <='s in thalassemia.
o Fven in certain rare disorders) abnormal erythrocyte morphology
may provide an important clue. Fxamples are acanthocytosis in
abetalipoproteinemia) stomatocytosis in the hereditary disorder of
this name) and numerous target cells in lecithin cholesterol
acyltransferase deficiency. Other laboratory studies of value in the
hereditary hemolytic disorders include the followingK
Hereditary spherocytosis * 4'H' greater than /(B)
incubated osmotic fragility studies autohemolysis in oxalate)
and detection of the underlying molecular defect
Hemoglobinopathies * -ickle cell preparation) Hb
electrophoresis at one or more pH) heat denaturation test for
unstable Hbs) oxygen disassociation for Hbs with abnormal
oxygen affinity
Thalassemia * .# and fetal Hb) Hb electrophoresis)
characteriation of the molecular defect) 1uantification of
alpha and beta chains
'ongenital dyserythropoietic anemias * Demonstration of
abnormalities of erythroid precursors in bone marrow
aspirates) positive acid hemolysis 2Ham9 test with normal
result of sucrose hemolysis test in one form of this disease
2hereditary erythroblastic multinuclearity with a positive
acidified serum test 3HF4>.-69
Hereditary <=' enymatic deficiencies * -pecific <='
enyme assay
o 0n clinical practice) approximately ;AB of hereditary <=' enymatic
deficiencies with significant clinical manifestations are either J*(*
>D deficiencies or abnormalities of pyruvic kinase. The age at
which a hemolytic disorder is detected is not always helpful in
determining whether the disorder is hereditary. .lthough the
abnormality is inherited) congenital manifestations may be unusual.
.n infant with sickle cell anemia or beta thalassemia appears
healthy at birth. 'linical manifestations usually do not occur in
infants younger than ( months because fetal Hb has not been
replaced by adult Hb until that age. 4ost patients with J*(*>D
deficiency have no manifestations of the erythrocyte enymatic
abnormality until they receive an oxidant drug.
o ,sually) thalassemia minor is not detected until a routine
hemogram is performed) and) then) it is often mistaken for iron
deficiency anemia because of the microcytosis and hypochromia.
Thus) the physician dealing with adult patients must be as aware of
these disorders as the pediatrician.
o The most commonplace of the hereditary disorders is J*(*>D
deficiency because it occurs in "AB of the .frican .merican
population living in the ,nited -tates. 0n this population) J*(*>D
deficiency usually remains undetected until oxidant drugs are
administered. Then) it produces a mild*to*moderate hemolytic
anemia that is transient in nature. 0n white populations of
4editerranean derivation) J*(*>D deficiency can produce a chronic
hemolytic anemia without exposure to drugs. Fxposure to oxidant
drugs can produce lethal hemolysis.
o .c1uired hemolytic disorders occur in a large number of disease
states and can vary considerably in severity. 0n addition) hemolysis
may be observed as a result of physical injury to the <=' or
following exposure to drugs) chemicals) or venoms. 0n many
patients) the etiology of the hemolytic disorder is apparent because
of other manifestations of the disease 2eg) infections) collagen
vascular disease9.
o . confirmed positive 'oombs test result can be extremely helpful in
this group of disorders. 0t provides assurance that the hemolytic
disorder is an ac1uired extracorpuscular defect and limits it to the
group of disorders associated with autoimmune hemolytic anemia.
They include the followingK
Drug*dependent antibodies 2eg) to penicillin) 1uinidine) alpha
methyldopa9
'oexistence of an underlying disease 2eg) hematologic
malignancies) lupus erythematosus) certain viral infections9
0diopathic groups in which an underlying disease cannot be
demonstrated
o ,sually) the ac1uired hemolytic disorders with intracorpuscular
defects are not difficult to diagnose. 5itamin =*"# and folic acid
deficiencies are associated with macrocytic anemia) the presence
of hypersegmented polymorphonuclear leukocytes in the peripheral
smear) megaloblastic bone marrow) physical findings of the
underlying cause of the deficiency state) and abnormal serum
levels for the deficient vitamin.
o 0ron deficiency in the ,nited -tates is rarely of sufficient severity to
cause significant hemolysis and is merely mentioned herein for the
sake of completeness.
o >aroxysmal nocturnal hemoglobinuria is diagnosed only if the
physician considers it in the differential diagnosis) and it may
manifest by either a pancytopenia or a hemoglobinuria. However) a
sugar*water test can help exclude this cause of hemolysis.
o The major diagnostic problem encountered with hemolytic disorders
is when the known causes for hemolysis have been excluded by
history) physical examination) and laboratory studiesC the 'oombs
test result is negativeC and not enough family members can be
tested to differentiate between hereditary intracorpuscular
hemolytic disorders and ac1uired extracorpuscular defects.
o . donor cell chromium survival study can be helpful in
differentiating between a hereditary hemolytic disorder and an
ac1uired hemolytic disorder. &abeled <='s from a healthy blood
donor of a compatible blood group allow for a normal survival rate
in patients with hereditary hemolytic disease and a shortened
lifespan in those with an ac1uired extracorpuscular defect.
Decreased <=' production
o Diminished production of <='s is suggested in all patients without
evidence of either blood loss or hemolysis. Thus) a patient with
anemia without evidence of bleeding or iron deficiency with normal
indirect bilirubin and normal or decreased reticulocyte count
probably has a defect in the production of erythrocytes. 4any of
these patients have pancytopenia or other abnormalities of the
leukocytes or the platelets that can be detected with an
examination of a peripheral smear. When this group of disorders is
suspected) the most important laboratory test is a bone marrow
biopsy and aspiration 2see >rocedures9. The bone marrow biopsy
permits categoriation of these disorders into / separate groupsK
2"9 aplastic or hypoplastic) 2#9 hyperplastic) and 2/9 bone marrow
replaced with nonhematopoietic elements 2infiltration of bone
marrow9 2see 0mage "9.
o Drugs or chemicals commonly cause the aplastic and hypoplastic
group of disorders. 'ertain types of these causative agents are
dose related and others are idiosyncratic. .ny human exposed to a
sufficient dose of inorganic arsenic) benene) radiation) or the usual
chemotherapeutic agents used for treatment of neoplastic diseases
develops bone marrow depression with pancytopenia. 'onversely)
among the idiosyncratic agents) only an occasional human exposed
to these drugs has an untoward reaction resulting in suppression of
" or more of the formed elements of bone marrow 2"K"AA to
"Kmillions9. With certain types of these drugs) pancytopenia is more
common) whereas with others) suppression of one cell line is
usually observed. Thus) chloramphenicol may produce
pancytopenia) whereas a granulocytopenia is more fre1uently
observed with toxicity to sulfonamides or antithyroid drugs.
o The idiosyncratic causes of bone marrow suppression include
multiple drugs in each of the categories that can be prefixed with
anti* 2eg) antibiotics) antimicrobials) anticonvulsants)
antihistamines9. The other idiosyncratic causes of known etiology
are viral hepatitis and paroxysmal nocturnal hemoglobinuria. 0n
approximately one half of patients presenting with aplastic anemia)
a definite etiology cannot be established) and the anemia must be
regarded as idiopathic.
o Whenever possible) a cause for the aplastic anemia should be
uncovered because cessation of exposure may lead to recovery.
0dentification of the offending agent is likewise important in
determining the prognosis.
o 'hances of survival are poorer for patients with idiosyncratic
aplasia caused by chloramphenicol and viral hepatitis and better
when paroxysmal nocturnal hemoglobinuria or anti*insecticides are
the probable etiology. The prognosis for idiopathic aplasia lies
between these # extremes) with an untreated mortality rate of
approximately (A*HAB within # years after diagnosis.
o <are causes of anemia due to a hypoplastic bone marrow include
familial disorders and the ac1uired pure red cell aplasias. The latter
are characteried by a virtual absence of erythroid precursors in the
bone marrow with normal numbers of granulocytic precursors and
megakaryocytes.
o .mong patients with a hyperplastic bone marrow and decreased
production of <='s) one group has an excellent prognosis) and the
other is unresponsive) refractory to therapy) and has a relatively
poor prognosis. The former includes patients with disorders of
relative bone marrow failure due to nutritional deficiency in whom
proper treatment with vitamin =*"#) folic acid) or iron leads to a
correction of anemia once the appropriate etiology is established.
Drugs acting as an antifolic antagonist or inhibitor of DE. synthesis
can produce similar effects. The second group includes patients
with an idiopathic hyperplasia that may respond partially to
pyridoxine therapy in pharmacologic doses but) more fre1uently)
does not. These patients have ringed sideroblasts in the bone
marrow indicating an inappropriate use of iron in the mitochondria
for heme synthesis.
o 'ertain patients with marrow hyperplasia may have refractory
anemia for years) but some of the group eventually develop acute
myelogenous leukemia.
o <are causes of diminished erythrocyte production with hyperplastic
bone marrow include hereditary orotic aminoaciduria and
erythremic myelosis.
o 0nfiltration of the bone marrow with fibrous tissue) neoplastic cells)
or other cells that replace normal hematopoietic tissue can diminish
the production of <='s) granulocytes) and platelets. The diagnosis
of myelofibrosis or neoplastic involvement of bone marrow is often
suggested by evidence of myeloid metaplasia in the peripheral
smear 2ie) erythroid and granulocyte precursors9. <eplacement of
bone marrow with nonhemopoietic cells leads to activation of fetal
sites of blood production in organs) such as the liver and the
spleen) with release of abnormally shaped erythrocytes and
normoblasts) immature granulocytes and normoblasts) immature
granulocytes) and large platelets into the peripheral blood. 4yeloid
metaplasia does not occur in aplastic disease. Thus) its presence in
a patient who is anemic suggests bone marrow infiltration) even
before the biopsy specimen is obtained.