Microcytic/hypochromic erythrocytes indicate some inadequacy
of structural matter, usually, not enough hemoglobin.
This is most commonly due to an inadequate dietary supply of iron (Fe
deficiency). In fact, iron deficiency anemia is the most common of all
Determining the cause of the Fe deficiency is of pivotal importance
in selecting appropriate therapy.
Remember, microcytic/hypochromic erythrocytes may also be seen in anemia
of chronic disease, in thalassemia and in the sideroblastic anemias.
Blood loss is the most common cause of iron deficiency.
Menstruation is the most likely reason in women ages 15 to 45 years.
Iron deficiency anemia in adult men and postmenopausal women is most
likely due to chronic gastrointestinal blood loss. Such losses are usually
secondary to ulcerating lesions [peptic ulcer disease, mucosal trauma
(hiatal hernias), drug ingestion (aspirin, nonsteroidal anti-inflammatory
drugs, steroids, potassium), parasitic infections, inflammatory bowel
disease and malignancy.
Lack of dietary iron may cause anemia in infancy when the daily
need for iron is not met by milk alone. This is why iron supplements
are given to infants. Iron deficiency is a major cause of anemia in
Malabsorption of iron is a rare cause of iron deficiency but
is seen in patients who have had a partial gastrectomy or who have a
Ferritin is in essence an "iron buffer", taking up excess
iron or releasing iron as needed. Small amounts of ferritin, derived
from iron stores, circulate in the plasma.
The amount of serum ferritin closely reflects iron stores, thus providing
a readily measured assessment of body iron stores.
1) ferritin increases in chronic inflammation;
2) ferritin is increased in hepatocellular disease; and
3) ferritin may be increased in malignancy.
Ferritin: When empty the ferritin shell is known as apoferritin.
Iron is stored as a hydrous Fe+++ oxide crystal.
Transferrin, the major iron transport protein, is synthesized
by the liver and macrophages.
Each molecule of transferrin can bind two atoms of iron. Usually about
one-third (25 - 45%) of the total transferrin is bound to iron (referred
to as % saturation).
Transferrin carries iron via plasma to cells throughtout the body,
though the most important site of delivery is to the marrow erythroblast.
Transferrin (diferric) binds to transferrin receptors (CD71) on the
erythroblast surface membrane.
The CD71 receptor-transferrin-iron complex is incorporated
into the cell by endocytosis. The endocytotic vacuole fuses with a lysozyme,
where at an acid pH, iron is released from transferrin as Fe++ and transported
to mitochondria where it is complexed with protoporphyrin IX forming
Non-heme iron (mainly Fe+++) is stabilized by gastric HCl; bound
to mucin and then transferred to a mucosal cell surface receptor.
Most heme iron is catabolized to Fe++ and tetrapyrrole in the mucosal
In the mucosal cell the iron is bound to mobilferrin, transported
through the cell to the submucosal capillary network where the iron
is oxidized to Fe+++, bound to transferrin and delivered via
the blood to the marrow and other tissues.
Note that some iron is stored or "trapped" as ferritin in the mucosal
cell. This "trapped" iron plays only a minor role in regulation of iron
intake/loss as it is readily overwhelmed by ingestion of inorganic iron.
Total Iron Binding Capacity approximates a measure of transferrin.
Serum iron is a measure of Fe bound to transferrin.
Normally 25 - 45% of transferrin is bound to iron, ie. the % saturation
In inflammatory and malignant conditions transferrin is decreased
possibly due to macrophage degradation.
Iron is decreased due to decreased release of Fe from macrophages
into the plasma.
Iron deficiency is best screened for with serum ferritin levels
(serum ferritin levels correspond to marrow stores).
A serum ferritin of <30 mg/L in men or <10 mg/L in women indicates
Ferritin, an acute phase reactant, may be elevated in inflammatory
conditions. Still, if the serum ferritin is not greater than 50 mg/L,
iron deficiency is likely.
The definitive test for iron deficiency is a Prussian blue stained
The upper image demonstrates an absence of iron in the bone marrow
macrophages of an individual with iron deficiency.
Compare the upper image with the lower image of a normal bone marrow
stained with Prussian blue and demonstrating coarse granular storage
iron in macrophages.
Iron deficiency develops gradually. Storage iron in the bone marrow
is the first to become depleted. Serum ferritin levels decrease (corresponding
to the marrow stores), while the Hct, Hgb and MCV remain normal, thus
a latent state.
In time, serum iron decreases and iron-binding capacity increases,
but there may be little or no evidence of anemia (small D in the Hct,
Hgb, and MCV).
Later, synthesis of hemoglobin becomes impaired by the lack of iron
and readily recognizable anemia results.
Eventually iron is lost from tissues other than blood including the
liver, skin and skeletal muscle.
Severe iron loss from epithelial tissues may result in koilonychia
(spoon nails) and/or angular cheilosis (ulcers and fissures at
the angle of the mouth).
Hct ... 14.4
Hgb ... 3.9
RBC ... 2.17
MCV ... 66.6
MCH ... 18.1
Erythropoiesis in iron deficiency is severely disrupted resulting
in anisocytosis (high RDW). With iron deficiency each developing erythrocyte
grabs whatever Fe is available, some get more, most get less! As a result
the RBCs tend to vary in size.
Patients with thalassemia trait (mild anemia), usually have a normal
RDW. In thalassemia, each erythrocyte has the same genetic defect, each
makes the same reduced amount of hemoglobin and so each RBC is about
the same size.
Caution! RDWs in Fe deficiency and thalassemia overlap and cannot be
used to definitively distinguish between the two.
Summary of laboratory findings in Fe deficiency anemia:
1. Decreased hematocrit and hemoglobin
2. Hypochromic microcytic RBCs on peripheral smear
3. Decreased serum iron and increased total iron binding capacity (TIBC)
4. Decreased bone marrow iron stores or decreased serum ferritin
The microcytic/hypochromic anemia of Fe deficiency must be distinguished
from anemia of chronic disease, from thalassemia and from sideroblastic
Blood loss the most common cause of iron deficiency (menstruation and
GI blood loss), but lack of dietary iron may be the cause in infancy
The oral administration of ferrous sulfate is the usual therapy
for Fe deficiency. The starting dose is 300 mg/day, increasing to 900
mg/day if tolerated, usually for 2 - 3 months.
Complications include nausea, abdominal cramps, constipation and diarrhea.
Iron medications should be stored away from children in "child proof"
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