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Other lower limits according to sex, age, and race, based on data from NHANES III and
Scripps-Kaiser studies, have been proposed (table 2) [3]. These values are as low as 12.7
g/dL for black men >60 years of age and 11.5 g/dL for black women >20 years of age.
There are a number of immediate limitations to this approach:
The above ranges may be "two-tailed" to be used for defining both anemia and
polycythemia. In such cases, 2.5 percent of normal adults will have values that are more
than 2 standard deviations below whatever "normal range" has been selected, and will
be considered anemic. On the other hand, some ranges are "one-tailed", such that 5
percent of normal subjects will have levels below the stated lower limit of normal [3].
The normal range for HGB and HCT is so wide that, for example, a male patient with a
baseline HCT of 49 percent may lose up to 15 percent of his RBC mass and still have a
HCT within the normal range.
"Normal" ranges may not apply to special populations (eg, high altitude living, smokers,
athletes, older adults). (See 'Special populations' below and "Approach to anemia in
adults with heart failure", section on 'Evaluation'.)
Setting a lower limit of normal for hemoglobin does not imply that such levels are
"optimal" in terms of morbidity and mortality. One study has suggested that the lower
limits of an optimal hemoglobin level, as assessed by all-cause mortality data, are 13.0
and 14.0 g/dL for elderly women and men, respectively [6]. However, in one report, older
black subjects classified as anemic by WHO criteria did not appear to be at risk for
adverse events such as mortality and mobility disability [7], suggesting that alternative
criteria for anemia might be required for this group (table 2) [3]. (See "Anemia in the
older adult", section on 'Defining anemia in the older adult'.)
Volume status HGB, HCT, and RBC count are all concentrations and dependent on the
red blood cell mass (RCM) as well as the plasma volume. As a result, values for all three
will be reduced if the RCM is decreased and/or if the plasma volume is increased [8].
Similarly, values for all three will be increased if the plasma volume is decreased (ie,
hemoconcentration). Three common clinical examples will help make this point:
Acute bleeding A 70 kg adult with a bleeding peptic ulcer who had a 750 mL
hematemesis (ie, 15 percent of a normal total blood volume) within the past 30 minutes
may have postural hypotension due to acute volume depletion, but will have normal
values for HGB and HCT. Over the ensuing 36 to 48 hours, most of the total blood volume
deficit will be repaired by the movement of fluid from the extravascular into the
intravascular space. Only at these later times will the HGB and HCT reflect blood loss.
However, if the total blood volume deficit is not fully repaired and the patient remains
hypovolemic, the HGB and HCT will underestimate the degree of blood loss [9].
Late pregnancy In the third trimester of pregnancy the RBC mass and plasma
volume are expanded by 25 and 50 percent, respectively, resulting in reductions in HGB,
HCT, and RBC count, often to anemic levels (figure 1). However, according to the RBC
mass, such women are polycythemic. The terms "physiologic" or "dilutional" anemia have
been applied to this setting.
Volume depletion Anemic patients admitted to the hospital in a volume depleted
(hemoconcentrated) state may not show abnormally low HGB/HCT values on initial
testing. Their underlying anemia may become apparent only after their volume status
has been corrected.
Special populations Normal ranges (table 1) may not be appropriate for all
populations:
Patients living at high altitude have values higher than those living at sea level [10].
(See "High altitude, air travel, and heart disease", section on 'Long-term altitude
exposure'.)
A study of blood donors who smoke found a significant and direct correlation between
the patients' blood carboxyhemoglobin and HGB values [11]. The same study also found
a significant relationship, although of lesser magnitude, between HGB values and the
degree of environmental air pollution with carbon monoxide in nonsmoking blood donors.
Thus, patients who smoke or have significant exposure to secondary smoke or other
sources of carbon monoxide may have hematocrits higher than normal [12], occasionally
reaching polycythemic levels. (See "Diagnostic approach to the patient with
polycythemia", section on 'Acquired secondary polycythemia'.)
Values for HGB in African-Americans of both sexes and all ages are 0.5 to 1.0 g/dL lower
than values in comparable Caucasian populations [3,13-17]. Some, but not all, of these
differences may be attributable to co-existing iron deficiency anemia and/or alpha
thalassemia [18].
Normal values for a population with a high incidence of chronic disease may be skewed
toward anemic levels. Thus, anemia may be difficult to define in countries in which
malnutrition, infection (eg, tuberculosis, malaria), and/or congenital hematologic
disorders (eg, thalassemia) are common. (See "Community public health issues and the
thalassemic syndromes: Lessons from other countries", section on 'Introduction'.)
Older adults Anemia in older adults is discussed separately. (See "Anemia in the older
adult".)
Athletes Values in male and female endurance athletes may vary significantly from
those in otherwise normal people [19-24]. Dilutional anemia secondary to an increased
plasma volume [20,25], gastrointestinal bleeding [21], intravascular hemolysis (eg,
march hemoglobinuria) [22], iron deficiency [26,27], as well as polycythemia [23,25]
have all been reported as a consequence of strenuous sports, or the use of performanceenhancing agents, such as androgens and erythropoietin. (See "Extrinsic nonimmune
hemolytic anemia due to mechanical damage: Fragmentation hemolysis and
hypersplenism", section on 'Mechanical trauma' and "Use of androgens and other
hormones by athletes", section on 'Androgens'.)
THE RBC LIFE CYCLE
Overview Erythropoiesis in the adult takes place within the bone marrow under the
influence of the stromal framework, cytokines, and the erythroid specific growth factor,
erythropoietin (EPO). EPO is a true endocrine hormone produced in the kidney by cells
that sense the adequacy of tissue oxygenation relative to the individual's metabolic
activity (figure 2). (See "Regulation of erythropoiesis".)
EPO enhances the growth and differentiation of the two erythroid progenitors: burst
forming units-erythroid (BFU-E) and colony forming units-erythroid (CFU-E) into
normoblasts of increasing maturity. The most mature of these, the orthochromatic
normoblast, extrudes its nucleus to form a red blood cell, via mechanisms that are still
unclear [28]. As such, the enucleate red blood cell still has a ribosomal network which,
when stained supravitally, identifies it as a reticulocyte, a cell still capable of a limited
amount of hemoglobin and protein synthesis [29].
The reticulocyte retains its ribosomal network (and its staining characteristics) for
approximately four days, of which three days are generally spent in the bone marrow and
one day in the peripheral blood (figure 3). The resulting mature RBC circulates for 110 to
120 days, after which it is removed from the circulation by macrophages that detect
senescent signals, primarily on the RBC membrane, through mechanisms that are poorly
understood. (See "Red blood cell survival: Normal values and measurement".)
Under steady state conditions, the rate of RBC production equals the rate of RBC loss.
Assuming, for ease of calculation, a survival of mature RBC of 100 days, 1 percent of
RBCs will be removed from the circulation each day. To achieve a constant RBC mass,
RBC losses must be replaced with an equal number of reticulocytes during the same time
period.
Reticulocytes normally survive in the circulation for one day; after this time they lose
their reticulum (RNA) and become mature red blood cells. Under steady-state conditions
reticulocytes will represent approximately 1 percent of total circulating RBC (table 1).
Since the normal RBC count is approximately 5 million/microL (5.0 x 10 12/liter), the bone
marrow must produce approximately 50,000 reticulocytes/microL of whole blood each
day in order to achieve a stable RBC mass. Lesser rates of RBC production, if persistent,
lead to anemia.
The rate of red cell production increases markedly under the influence of high levels of
erythropoietin (EPO). A normal bone marrow replete with iron, folate, and cobalamin can
increase erythropoiesis in response to EPO approximately fivefold in adults and seven- to
eight-fold in children. Thus, under optimal conditions, steady-state absolute reticulocyte
counts as high as 250,000/microL (2.5 x 1011/liter) are possible in the adult.
Reticulocytes Reticulocytes can be enumerated manually after supravital staining of a
blood sample with dyes such as new methylene blue (picture 2). The normal range (ie,
percent of RBC with positive staining) in adults is 0.5 to 2.0 percent (table 1).
Reticulocytes can be appreciated on a standard blood smear stained with Wright Giemsa
as RBC with a blue tint (polychromatophilia) that are larger than mature RBC, with
irregular borders and a lack of central pallor (picture 3).
Reticulocytes can be counted with more accuracy via automated blood counters after
staining with a fluorescent dye such as thiazole orange, which binds to the RNA of
reticulocytes [30]. (See "Automated hematology instrumentation", section on 'Automated
counting of reticulocytes'.)
The utility of reticulocyte counting in some settings can be improved by determination of
the absolute reticulocyte count, the corrected absolute reticulocyte count, and/or the
reticulocyte production index. This subject is discussed separately. (See "Approach to the
diagnosis of hemolytic anemia in the adult", section on 'Reticulocyte response'.)
CLINICAL CONSEQUENCES The signs and symptoms induced by anemia are dependent
upon the degree of anemia and the rate at which it has evolved, as well as the oxygen
demands of the patient. Symptoms are much less likely with anemia that evolves slowly,
because there is time for multiple homeostatic forces to adjust to a reduced oxygen
carrying capacity of blood.
Normal red cell function RBCs carry oxygen linked to hemoglobin from the lungs to
tissue capillaries. Oxygen is then released from hemoglobin according to the
characteristics of the oxyhemoglobin dissociation curve, with each gram of hemoglobin
carrying 1.3 mL of oxygen. Thus, approximately 20 mL/dL (or 20 volumes percent) can be
carried by 15 g/dL of hemoglobin at full saturation. Approximately 5 volumes percent (25
percent of the total) is normally removed by the tissues [31]. (See "Oxygen delivery and
consumption" and "Genetic disorders of hemoglobin oxygen affinity", section on
'Mutations that decrease the affinity of hemoglobin for 2,3-BPG'.)
Symptoms Symptoms related to anemia can result from two factors: decreased
oxygen delivery to tissues, and, in patients with acute and marked bleeding, the added
insult of hypovolemia. There is some reduction in blood volume but not plasma volume
after acute severe hemolysis, due to the fall in RBC mass. In comparison, total blood
volume remains normal in anemia due to chronic, low-grade bleeding, since there is
ample time for equilibration with the extravascular space and renal retention of salt and
water.
Symptoms of impaired oxygen delivery reflect the fall in hemoglobin concentration. The
extraction of oxygen by the tissues can increase from a baseline of 25 percent to a
maximum of about 60 percent in the presence of anemia or hypoperfusion. Thus, normal
oxygen delivery of 5 volumes percent can be maintained by enhanced extraction alone
down to a hemoglobin concentration of 8 to 9 g/dL [32].
When the added compensation of increases in stroke volume and heart rate (and
therefore cardiac output) are included, oxygen delivery can be maintained at rest at a
hemoglobin concentration as low as 5 g/dL (equivalent to a hematocrit of 15 percent),
assuming that the intravascular volume is maintained [33]. (See "Indications and
hemoglobin thresholds for red blood cell transfusion in the adult", section on 'Role of
blood in oxygen delivery'.)
Symptoms will occur when the hemoglobin concentration falls below this level at rest, at
higher hemoglobin concentrations during exertion, or when cardiac compensation is
impaired because of underlying heart disease. The primary symptoms include exertional
dyspnea, dyspnea at rest, varying degrees of fatigue, and signs and symptoms of the
hyperdynamic state, such as bounding pulses, palpitations, and "roaring in the ears".
More severe anemia may lead to lethargy and confusion and potentially life-threatening
complications such as congestive failure, angina, arrhythmia, and/or myocardial
infarction. (See "High-output heart failure".)
Anemia induced by acute bleeding is associated with the added complication of
intracellular and extracellular volume depletion. The earliest symptoms include easy
fatigability, lassitude, and muscle cramps. This can progress to postural dizziness,
lethargy, syncope, and, in severe cases, to persistent hypotension, shock, and death.
(See "Etiology, clinical manifestations, and diagnosis of volume depletion in adults".)
Mortality The development of anemia is a risk factor for increased mortality in a
number of clinical settings. A few of the many examples are listed below:
Chronic kidney disease (see "Anemia and left ventricular hypertrophy in chronic kidney
disease", section on 'General cardiovascular outcomes')
Malignancy (see "Role of erythropoiesis-stimulating agents in the treatment of anemia
in patients with cancer", section on 'Effect on disease control and survival')
Heart failure (see "Approach to anemia in adults with heart failure", section on
'Prognosis')
The older adult (see "Anemia in the older adult", section on 'Increased mortality')
The hospitalized adult [34] (see "Indications and hemoglobin thresholds for red blood
cell transfusion in the adult", section on 'Impact of anemia on morbidity and mortality')
Fatigue Although anemia may be associated with fatigue, this complaint is nonspecific, may be present in a number of other conditions, and may be multi-factorial. This
subject is discussed in depth separately. (See "Approach to the adult patient with fatigue"
and "Cancer-related fatigue: Prevalence, screening and clinical assessment".)
CAUSES OF ANEMIA There are two general approaches one can use to help identify the
cause of anemia:
A kinetic approach, addressing the mechanism(s) responsible for the fall in hemoglobin
concentration
A morphologic approach categorizing anemias via alterations in RBC size (ie, mean
corpuscular volume) and the reticulocyte response [35].
Kinetic approach Anemia can be caused by one or more of three independent
mechanisms: decreased RBC production, increased RBC destruction, and blood loss [29].
Decreased RBC production Anemia will ultimately result if the rate of RBC production is
less than that of RBC destruction. (See "Anemias due to decreased red cell production".)
The more common causes for reduced (effective) RBC production include:
Lack of nutrients, such as iron, B12, or folate. This can be due to dietary lack,
malabsorption (eg, pernicious anemia, sprue), or blood loss (iron deficiency).
Bone marrow disorders (eg, aplastic anemia, pure RBC aplasia, myelodysplastic
syndromes, tumor infiltration)
Bone marrow suppression (eg, drugs, chemotherapy, irradiation) (see "Hematologic
consequences of malignancy: Anemia and bleeding")
Low levels of trophic hormones, which stimulate RBC production, such as EPO (eg,
chronic renal failure), thyroid hormone (eg, hypothyroidism), and androgens (eg,
hypogonadism)
A rare cause of anemia due to reduced EPO production has been described in patients
with autonomic dysfunction and orthostatic hypotension [36,37]. (See "Treatment of
orthostatic and postprandial hypotension", section on 'Erythropoietin'.)
Acquired inhibitors of EPO or the EPO receptor have also been described as causes of
anemia [38]. (See "Pure red cell aplasia due to anti-erythropoietin antibodies".)
The anemia of inflammation, associated with infectious, inflammatory, or malignant
disorders, is characterized by reduced availability of iron due to decreased absorption
from the gastrointestinal tract and decreased release from macrophages, a relative
reduction in erythropoietin levels, and a mild reduction in RBC lifespan. (See "Anemia of
chronic disease (anemia of [chronic] inflammation)".)
Increased RBC destruction A RBC life span below 100 days is the operational definition
of hemolysis [39]. (See "Red blood cell survival: Normal values and measurement".)
Anemia will ensue when the bone marrow is unable to keep up with the need to replace
more than about 5 percent of the RBC mass per day, corresponding to a RBC survival of
about 20 days. (See "Approach to the diagnosis of hemolytic anemia in the adult".)
Examples include (table 3):
Inherited hemolytic anemias (eg, hereditary spherocytosis, sickle cell disease,
thalassemia major)
Acquired hemolytic anemias (eg, Coombs'-positive autoimmune hemolytic anemia,
thrombotic thrombocytopenic purpura, malaria, paroxysmal nocturnal hemoglobinuria)
Blood loss Iron deficiency in the United States and Western Europe is almost always
due to blood loss, which may be obvious, occult, or underappreciated, as follows:
computer programs that "flag" for the presence of abnormalities such as anisocytosis
(cells of varying size), microcytosis, macrocytosis, and hypochromia (reduced hemoglobin
content per cell) [47]. (See "Automated hematology instrumentation", section on 'Red
cell distribution width'.)
Macrocytic anemia Anemia is considered "macrocytic" when the MCV exceeds 100 fL
(femtoliters) (table 5) Causes include the following. (See "Macrocytosis".)
An increased MCV is a normal characteristic of reticulocytes (picture 3). Any condition
causing marked reticulocytosis will be associated with an increased MCV.
Abnormal nucleic acid metabolism of erythroid precursors (eg, folate or cobalamin
deficiency and drugs interfering with nucleic acid synthesis, such as zidovudine and
hydroxyurea) may lead to macrocytosis and anemia
Abnormal RBC maturation (eg, myelodysplastic syndrome, acute leukemia, LGL
leukemia).
Other common causes include alcohol abuse, liver disease, and hypothyroidism.
A report from a family practice group found macrocytosis in 2 to 4 percent of patients
[48], while a study of 1784 randomly selected older adults living at home found
macrocytosis in 6.3 percent of men and 3.3 percent of women [49]. The most common
causes were alcoholism, liver disease, hypothyroidism, and the megaloblastic anemias
(eg, folate or B12 deficiency).
Microcytic anemia Anemia is considered "microcytic" when the MCV is less than 80 fl.
Microcytosis is usually accompanied by a decreased hemoglobin content within the RBC
(mean corpuscular hemoglobin, MCH), with a parallel reduction in MCV, producing a
hypochromic (low MCH) as well as a microcytic (low MCV) appearance on the blood
smear (picture 4 and table 4). (See "Mean corpuscular volume", section on 'Causes of
microcytosis'.)
The following pathologic processes lead to the production of hypochromic microcytic red
cells:
Reduced iron availability Severe iron deficiency, the anemia of inflammation, copper
deficiency
Acquired disorders of heme synthesis Lead poisoning, acquired sideroblastic anemias
Reduced globin production Thalassemic disorders, other hemoglobinopathies
Rare congenital disorders including sideroblastic anemias, porphyria, and defects in
iron absorption, transport, utilization, and recycling [50,51]
The three most common causes of microcytosis in clinical practice are iron deficiency,
alpha or beta thalassemia minor, and (less often) the anemia of inflammation (anemia of
chronic disease). Since all may have hypochromic and microcytic RBCs, other tests must
be used to establish the diagnosis.
Iron deficiency anemia Important discriminating features are a low serum ferritin
concentration, an increased total iron binding capacity (transferrin), and low serum iron
concentration (table 6). For clinicians making this diagnosis, it is mandatory to determine
the cause of the iron deficient state (eg, occult colonic carcinoma, excessive menstrual
losses). (See "Causes and diagnosis of iron deficiency anemia in the adult".)
Alpha or beta thalassemia minor Adults with thalassemia are most often
heterozygotes for the alpha or beta forms of this syndrome, and may be only minimally
anemic. A family history is therefore often negative. Physical examination may reveal
splenomegaly; the peripheral smear shows varying degrees of hypochromia,
microcytosis, target cells (picture 5), tear-drop forms, and basophilic stippling (picture 6).
The RBC count may actually be increased; uncomplicated patients have normal or
increased iron stores. (See "Clinical manifestations and diagnosis of the thalassemias".)
The diagnosis of beta thalassemia trait can often be made by demonstrating increased
levels of hemoglobin A2 on hemoglobin electrophoresis or liquid chromatography (HPLC),
while molecular methods are usually required for the diagnosis of the alpha thalassemia
variants [52]. (See "Laboratory diagnosis of the hemoglobinopathies".)
Anemia of inflammation The hallmarks of this condition include a low serum iron,
low total iron binding capacity (transferrin), and a normal to increased serum ferritin
concentration. Although hypochromic and microcytic red cells can be found in these
patients, a low MCV is most frequently seen only in those patients with hepatoma or
renal cell carcinoma. (See "Anemia of chronic disease (anemia of [chronic]
inflammation)".)
Normocytic anemia By definition, the mean RBC volume is normal (ie, MCV between
80 and 100 fL) in patients with normocytic anemia (table 4). Approach to this extremely
large category of patients can be narrowed somewhat by examination of the blood smear
to determine if there is a subpopulation of RBCs with distinctive size or shape
abnormalities which would place the patient in one of the above categories (ie, early
microcytic or macrocytic anemia), or by use of the kinetic approach to determine the
mechanism(s) underlying the anemia (see 'Kinetic approach' above and 'Systemic
disorders' below).
Systemic disorders Anemia may be the first manifestation of a systemic disorder,
along with other nonspecific complaints such as fever, weight loss, anorexia, and
malaise. Simple laboratory tests may give additional clues toward the underlying disease
process. These include abnormalities on the urinalysis or routine chest x-ray, liver or
renal function tests, erythrocyte sedimentation rate, C-reactive protein, serum protein
electrophoresis, WBC count and differential, and reduced (or increased) platelet counts.
Anemia in older adults, which may be difficult to categorize, is discussed separately. (See
"Anemia in the older adult".)
Anemia of chronic renal disease Anemia is a common complication of renal disease,
and may be multifactorial. This subject is discussed in detail separately. (See "Overview
of the management of chronic kidney disease in adults", section on 'Anemia'.)
Cardiorenal anemia syndrome Cardiorenal anemia syndrome refers to the
simultaneous presence of anemia, heart failure, and chronic renal disease [53]. This
disorder complex is discussed separately. (See "Anemia and left ventricular hypertrophy
in chronic kidney disease" and "Approach to anemia in adults with heart failure".)
Cancer-associated anemia Anemia in patients with malignancy is often multi-factorial
and related to the underlying malignancy as well as its treatment. (See "Hematologic
consequences of malignancy: Anemia and bleeding".)
Acquired anemia in hospitalized patients The development of anemia in a previously
non-anemic patient subsequent to hospitalization (hospital-acquired anemia, HAA) is
usually multifactorial and includes causes such as bleeding following an invasive
procedure or surgery, large volumes of blood drawn for diagnostic studies, occult
bleeding, hemodilution from intravenous fluid administration, as well as a blunted
erythropoietic response associated with critical illness [41,54,55]. As examples:
Red blood cell indices Three RBC indices are usually measured by automated blood
counters: mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and
mean corpuscular hemoglobin concentration (MCHC) (table 1). The values for MCH and
MCHC generally parallel the information obtained from the MCV (ie, larger or smaller
RBCs tend to have higher or lower values for MCH, respectively).
Mean corpuscular volume The normal range for the mean corpuscular volume (MCV) is
80 to 100 femtoliters (fL). The causes of anemia associated with a low (microcytosis) or
high (macrocytosis) MCV are discussed above (table 4) (see 'Morphologic approach'
above).
Values of the MCV in excess of 115 fL are almost exclusively seen in vitamin B12 or
folate deficiency.
Even higher values can occur as an artifact when cold agglutinins are present, which
causes RBCs to go through the counting aperture in automated instruments in doublets
or triplets [63]. Warming the specimen (and reagents) to body temperature prior to a
repeat count should return the MCV to normal and confirm the presence of a cold
agglutinin. (See "Mean corpuscular volume".)
Mean corpuscular hemoglobin The normal mean corpuscular hemoglobin (MCH)
ranges from 27.5 to 33.2 picograms of hemoglobin per RBC. Low values are seen in iron
deficiency and thalassemia, while increased values occur in macrocytosis of any cause.
Mean corpuscular hemoglobin concentration The mean normal value for the MCHC is
34 grams of hemoglobin per dL of RBCs (340 g/L of RBCs). The 95 percent confidence
limits for the MCHC have been variably given (table 1), with lower and upper limits of 31
to 33 and 35 to 36, respectively. Low values occur in the same conditions that generate
low values for MCV and MCH, while increased values occur almost exclusively in the
presence of congenital or acquired spherocytosis or in other congenital hemolytic
anemias in which red cells are abnormally desiccated (eg, sickle cell anemia, hemoglobin
C disease, xerocytosis). (See "Hereditary spherocytosis: Clinical features, diagnosis, and
treatment" and "Xerocytosis".)
Reticulocyte count The reticulocyte count, either as a percentage of all RBCs, the
absolute reticulocyte count, the corrected absolute reticulocyte count, or as the
reticulocyte production index, helps to distinguish among the different types of anemia:
Anemia with a high reticulocyte count reflects an increased erythropoietic response to
continued hemolysis or blood loss (see 'Reticulocytes' above).
A stable anemia with a low reticulocyte count is strong evidence for deficient
production of RBCs (ie, a reduced marrow response to the anemia). (See "Anemias due to
decreased red cell production".)
Hemolysis or blood loss can be associated with a low reticulocyte count if there is a
concurrent disorder that impairs RBC production (eg, infection, prior chemotherapy, other
causes for bone marrow suppression) (see 'Multiple causes of anemia' below).
A low reticulocyte percentage accompanied by pancytopenia (ie, the combination of
anemia, thrombocytopenia, and neutropenia) is suggestive of aplastic anemia, while an
extremely low or zero reticulocyte percentage with normal white blood cell and platelet
counts suggests a diagnosis of pure red cell aplasia. (See "Aplastic anemia: Pathogenesis;
clinical manifestations; and diagnosis" and "Acquired pure red cell aplasia in the adult".)
White blood cell count and differential A low total white blood cell (WBC) count
(leukopenia) in a patient with anemia should lead to consideration of bone marrow
may
be
important,
suggesting
detailed. These articles are written at the 10 th to 12th grade reading level and are best for
patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you
to print or e-mail these topics to your patients. (You can also locate patient education
articles on a variety of subjects by searching on "patient info" and the keyword(s) of
interest.)
Basics topics (see "Patient information: Anemia of chronic disease (The Basics)")
Beyond the Basics topics (see "Patient information: Anemia caused by low iron (Beyond
the Basics)")
SUMMARY AND RECOMMENDATIONS The initial approach to the patient with anemia is
to perform a complete history and physical examination along with a review of the results
of a complete blood count (CBC) with white blood cell differential, platelet count,
reticulocyte count, and an examination of the peripheral blood smear (table 1). (See
'Evaluation of the patient' above.)
A HGB <13.5 g/dL (<135 g/L) or a HCT <41.0 percent represents anemia in men; a value
<12.0 g/dL (<120 g/L) or <36.0 percent, respectively, represents anemia in women.
Differences may also exist between races, in older adults, and in athletes. (See
'Definitions' above and 'Special populations' above.)
Diagnostic approach: morphology According to the morphologic approach, the anemia
is first classified via the red cell size (ie, mean corpuscular volume, MCV), which is part of
the CBC (algorithm 1):
Microcytic anemias are associated with an MCV below 80 fL. The most commonly seen
causes are iron deficiency (table 4 and table 6), thalassemia, and the anemia of (chronic)
inflammation (see 'Microcytic anemia' above and 'Evaluation for iron deficiency' above).
Macrocytic anemias are characterized by an MCV above 100 fL (table 4 and table 5).
The most common causes include alcoholism, liver disease, folate and vitamin B12
deficiency, and myelodysplasia. (See "Macrocytosis", section on 'Evaluation'.)
The MCV is between 80 and 100 fL in patients with normocytic anemia (table 4). This is
an extremely large and amorphous category, which can be narrowed somewhat by
examination of the blood smear to determine if there is a small population of red cells
with distinctive size or shape abnormalities which would place the patient in one of the
above categories (ie, early microcytic or macrocytic anemia), or would raise suspicion of
an acute or chronic hemolytic state (eg, spherocytes, sickle forms, ovalocytes).
Hemolysis may have been suspected from the patient's history, physical examination,
or examination of the peripheral blood smear (eg, sudden onset of anemia, jaundice,
splenomegaly, presence of spherocytes or schistocytes or other red cell shape changes)
(see 'Evaluation of the patient' above). It is confirmed by the finding of increased levels
of indirect bilirubin and lactate dehydrogenase, and low levels of haptoglobin (table 3).
(See 'Evaluation for hemolysis' above and "Approach to the diagnosis of hemolytic
anemia in the adult", section on 'Diagnostic approach'.)
The presence of abnormal cells in the circulation (eg, nucleated RBCs, blasts, atypical
mononuclear cells) and/or abnormal increases or decreases in absolute counts for
granulocytes, lymphocytes, monocytes, or platelets (algorithm 1) suggests that the
anemia is part of a more complex hematologic disorder (eg, leukemia, aplastic anemia,
myelodysplastic syndrome, myeloproliferative neoplasm). Consultation with a
hematologist would be appropriate at this point.
Anemia may be the first manifestation of a systemic disorder (table 4), along with other
nonspecific complaints such as fever, weight loss, anorexia, and malaise. Simple
laboratory tests may give additional clues toward the underlying disease process. These
include abnormalities on the urinalysis or routine chest x-ray, elevated serum creatinine,
abnormal liver function tests, and increased erythrocyte sedimentation rate or C-reactive
protein.
Diagnostic approach: kinetics According to the kinetic approach, the following three
questions are asked in order to determine the mechanism(s) causing the anemia. (See
'Causes of anemia' above.)
Is there evidence for decreased red cell production? (See 'Decreased RBC production'
above.)
Is there evidence for increased red cell destruction (hemolysis)? (See 'Increased RBC
destruction' above.)
Is there a history of bleeding? (See 'Blood loss' above.)