Iron Deficiency
Clinical features
When iron deficiency is developing,
the reticuloendothelial stores (haemosiderin and ferritin) become completely
depleted before anaemia occurs (Fig. 3.6). As the condition develops, the
patient may show the general symptoms and signs of anaemia (see p. 20) and also
a painless glossitis, angular stomatitis, brittle, ridged or spoon nails
(koilonychia) (Fig. 3.7) and unusual dietary cravings (pica). The cause of the
epithelial cell changes is not clear but may be related to reduction of
iron‐containing enzymes. In children, iron deficiency is particularly
significant as it can cause irritability, poor cognitive function and a decline
in psychomotor development. There is also evidence that oral or parenteral iron
may reduce fatigue in iron‐deficient (low serum ferritin) non‐anaemic women.
Causes of iron deficiency
In developed countries, chronic
blood loss, especially uterine or from the gastrointestinal tract, is the
dominant cause of iron deficiency (Table 3.4) and dietary deficiency is rarely
a cause on its own. Five hundred
millilitres of blood contain approximately 250 mg iron and, despite the
increased absorption of food iron at an early stage of iron deficiency,
negative iron balance is usual in chronic blood loss.
Increased demands during infancy,
adolescence, pregnancy, lactation and in menstruating women account for the
high risk of iron deficiency anaemia in these particular clinical groups.
Newborn infants have a store of iron derived from delayed clamping of the cord
and the breakdown of excess red cells. From 3 to 6 months there is a tendency
for negative iron balance because of growth. From 6 months, supplemented
formula milk and mixed feeding, particularly with iron‐forti-fied foods,
prevents iron deficiency.
In pregnancy increased iron is needed
for an increased maternal red cell mass of approximately 35%, transfer of 300
mg of iron to the fetus and because of blood loss at delivery. Although iron
absorption is also increased, iron therapy is often needed if the haemoglobin
(Hb) falls below 100 g/L or the mean cell
volume (MCV) is below 82 fL in the third trimester.
Menorrhagia (a loss of 80 mL or more
of blood at each cycle) is difficult to assess clinically, although the loss of
clots, the use of large numbers of pads or tampons or prolonged periods all suggest
excessive loss.
It takes about 8 years for a normal
adult male to develop iron deficiency anaemia solely as a result of a poor diet
or malabsorption resulting in no iron intake at all. In developed countries
inadequate intake or malabsorption are only rarely the sole cause of iron
deficiency anaemia. Gluten‐induced enteropathy, partial or total gastrectomy
and atrophic gastritis (often autoimmune and with Helicobacter pylori infection)
may, however, predispose to iron deficiency. In developing countries, iron
deficiency may occur as a result of a life‐long poor diet, consisting mainly of
cereals and vegetables. Hookworm may aggravate iron deficiency, as may repeated
pregnancies or growth and menorrhagia in young females.
Laboratory findings
These are summarized and contrasted
with those in other hypochromic anaemias in Table 3.7.
Red cell indices and blood film
Even before anaemia occurs, the red
cell indices fall and they fall progressively as the anaemia becomes more
severe. The blood film shows hypochromic, microcytic cells with occasional
target cells and pencil‐shaped poikilocytes (Fig. 3.8). The reticulocyte count
is low in relation to the degree of anaemia. When iron deficiency is associated
with severe folate or vitamin B12 deficiency, a ‘dimorphic’ film occurs with a
dual population of red cells of which one is macrocytic and the other
microcytic and hypochromic; the indices may be normal. A dimorphic blood film
is also seen in patients with iron deficiency anaemia who have received recent
iron therapy and produced a population of new haemoglobinized normal‐sized red
cells (Fig. 3.9) and when the patient has been transfused. The platelet count
is often moderately raised in iron deficiency, particularly when haemorrhage is
continuing.
Bone marrow iron
Bone marrow examination is not
essential to assess iron stores except in complicated cases. In iron deficiency
anaemia there is a complete absence of iron from stores (macrophages) and from
developing erythroblasts (Fig. 3.10). The erythroblasts are small and have a
ragged cytoplasm.
Serum iron and total
iron‐binding capacity
The serum iron falls and total
iron‐binding capacity (TIBC) rises so that the TIBC is less than 20% saturated
(Fig. 3.11). This contrasts both with the anaemia of chronic disorders (see below), when the serum
iron and the TIBC are both reduced, and with other hypochromic anaemias where
the serum iron is normal or even raised.
Serum ferritin
A small fraction of body ferritin
circulates in the serum, the concentration being related to tissue,
particularly reticuloendothelial, iron stores. The normal range in men is
higher than in women (Fig. 3.11). In iron deficiency anaemia the serum ferritin
is very low while a raised serum ferritin indicates iron overload or excess
release of ferritin from damaged tissues or an acute phase response (e.g. in
inflammation). The serum ferritin is normal or raised in the anaemia of chronic
disorders.
Investigation of the cause of iron
deficiency (Fig. 3.12)
In premenopausal women, menorrhagia
and/or repeated preg nancies are the usual causes of the deficiency. If these
are not present, other causes must be sought. Insome patients with menorrhagia
a clotting or platelet abnormality (e.g. von Willebrand disease) is present. In
men and postmenopausal women, gastrointestinal blood loss is the main cause of
iron deficiency and the exact site is sought from the clinical history,
physical and rectal examination, by occult blood tests, and by appropriate use
of upper and lower gastrointestinal endoscopy and/or radiology (e.g. computed
tomography (CT) of the pneumocolon) or virtual colonoscopy using the 3D colon
system (Figs 3.12 and 3.13). Tests for parietal cell antibodies, Helicobacter
infection and serum gastrin level may help to diagnose autoimmune
gastritis. In difficult cases a camera in a capsule can be swal lowed which
relays pictures of the gastrointestinal tract electronically. Tests for
transglutaminase antibodies and duodenal biopsy to look for gluten‐induced
enteropathy can be valuable. Hookworm ova are sought in stools of subjects from
areas where this infestation occurs. Rarely, a coeliac axis angiogram is needed
to demonstrate angiodysplasia.
If gastrointestinal blood loss is
excluded, loss of iron in the urine as haematuria or haemosiderinuria (resulting
from chronic intravascular haemolysis) is considered. A
normal chest X‐ray excludes the rare condition of pulmonary haemosiderosis.
Rarely, patients bleed themselves producing iron deficiency.
Treatment
The underlying cause is treated as far
as possible. In addition, iron is given to correct the anaemia and replenish
iron stores.
Oral iron
The best preparation is ferrous
sulphate which is cheap, contains 67 mg iron in each 200‐mg tablet and is best
given on an empty stomach in doses spaced by at least 6 hours. Ferrous fumarate is equally cheap and
effective. If side‐effects occur (e.g. nausea, abdominal pain, constipation or
diarrhoea), these can be reduced by giving iron with food or by using a
preparation of lower iron content (e.g. ferrous gluconate which contains less
iron (37 mg) per 300‐mg tablet). An elixir is available for children.
Slow‐release preparations should not be used.
Oral iron therapy should be given
for long enough both to correct the anaemia and to replenish body iron stores,
which usually means for at least 6 months. The haemoglobin should rise at the rate of approximately 20 g/L every 3
weeks. Failure of response to oral iron has several possible causes (Table 3.5)
which should all be considered before parenteral iron is used. Iron fortification
of the diet in infants in Africa reduces the incidence of anaemia but increases
suceptibility to malaria.
Parenteral iron
Many different preparations are
available with varying licens ing in different countries.The dose is
calculated according to body weight and degree of anaemia. Iron dextran
(CosmoFer®) can be given as slow intravenous injection or infusion either
in small
single doses or
as a total
dose infusion given
in 1 day. Ferric carboxymaltose
(Ferinject®) and ferric isomaltoside (Monofer) may also be given as a total
dose in 1 day by slow intravenous
infusion. Ferric hydroxide–sucrose (Venofer®)
is administered by slow
intravenous injection or
infusion, to a maximum
of 200 mg iron
in each infusion.
Ferumoxytol (Feraheme®) is licensed for chronic renal failure. There may
be hypersensitivity or anaphylactoid reactions to parenteral iron,
especially in those
with a previous
reaction, multiple drug allergies and severe atopy. If the
reaction is severe, it is treated with
intravenous hydrocortisone and
possibly adrenaline. Parenteral
iron is given slowly and only when there are high iron requirements as in
gastrointestinal bleeding, severe menorrhagia, chronic haemodialysis, with
erythropoietin therapy, and when oral
iron is ineffective
(e.g. iron malabsorption resulting from gluten‐induced
enteropathy or atrophic gastritis) or impractical (e.g. active Crohn’s
disease). The haematological response to parenteral iron is no faster than to
adequate dosage of oral iron but the stores are replenished faster. Intravenous
iron has also been found to increase functional capacity and quality of life in
some patients with congestive heart failure, even in the absence of anaemia
(see p. 326).
