Non-Anaemic Iron Deficiency

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Non-Anaemic Iron Deficiency (NAID) (Causes,
Symptoms, and Treatment)

• ANWER GHANI
• FIBMS
• IRAQ

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Within the body, iron has roles other than
haemoglobin synthesis.

• Iron deficiency (ID) and anaemia are not
  synonymous patients with ID can present with
  symptoms without having anaemia.
• Therefore iron deficiency without anaemia must be
  recognised as a clinical diagnosis on its own.

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• Iron deficiency is a reduced content of total
  body iron.
• Iron-deficiency anaemia (IDA) occurs when the
  iron deficiency is sufficient to reduce
  erythropoiesis and therefore the haemoglobin (Hb)
  level falls.
• However, problems related to iron depletion can
  develop before this stage.

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Non-anaemic iron deficiency (NAID) is sometimes
termed 'latent iron deficiency' or 'depleted iron
stores. I think that ( Iron Deficiency) is the
best term, but it is good to use (NON ANAEMIC
IRON DEFICIENCY) for a while to alert people to
the problem and that lack of iron does not mean
anemia only.
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Iron depletion may be three times as common as
iron deficiency anaemia (IDA), which has a
prevalence of 2-5.
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Risk factors Non-anaemic Iron Deficiency -Children
and adolescents -The elderly -Women of
childbearing age ( Iron deficiency may be an
under-recognised cause of fatigue in women of
childbearing age.) -Obesity (The mechanism is not
fully understood, but may involve reduced
absorption of iron from the upper GI tract,
increased requirements and/or the impact of
obesity-related inflammation.
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Causes of Non-anaemic Iron Deficiency Inadequate
intake Plant-based diets with little meat. Low
calorie intake in relation to iron requirement
Malabsorption - eg, coeliac disease. Excessive
consumption of foods which reduce absorption -
eg, cow's milk, tea. Achlorhydria (gastric acid
maintains ferric iron in solution, so aids
absorption) - eg, from proton pump inhibitors or
post-gastrectomy. Helicobacter pylori
colonisation (possibly) reduces iron
uptake. Excessive loss (bleedings) Functional
iron deficiency (Chronic diseases) Patients
with heart failure should be screened for iron
level even if they are not anaemic, as treatment
of depletion can improve prognosis11.
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Symptoms There may be no symptoms. Fatigue. Poor
work productivity. Poor attention and
memory. Sore tongue. Poor condition of skin,
nails or hair, including hair loss. Delayed skin
wound healing. Developmental delay. Restless legs
syndrome. Signs There may be no signs. Angular
cheilitis or angular stomatitis. Atrophic
glossitis. Nails which may show brittleness. Poor
condition of skin or hair.
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Anaemia is a late manifestation of ID
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Iron deficiency in pregnancy Compared to
non-iron-deficient women, gravidas with depleted
iron stores at the start of pregnancy are more
likely to develop pre- and postnatal ID and have
a newborn with a lower birth weight. ID has been
associated with mental illness and impaired
neurocognitive functions, such as poor memory and
slower neural processing, which may be due to ID
irrespective of anaemia. Postnatal ID is linked
to neonatal iron status and foetal iron loading,
and is associated with permanent cognitive and
behavioural effects that are measurable until up
to 19 years of age, even with postnatal iron
repletion. Mothers should be screened and
treated for ID before conception. Furthermore,
newborns should be screened and treated for ID
after birth to avoid permanent neurocognitive
damage.
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DIAGNOSIS Serum ferritin assay has become the
standard test for the assessment of iron
stores. The WHO defines low ferritin as levels
lt15 µg/L for adults and lt12 µg/L for children.
However, in clinical practice, when ferritin
levels dip below 30 µg/L, ID can be
ascertained. Ferritin is an acute-phase
reactant that is increased in serum during
chronic inflammation. Cut-off values for ferritin
in ID are increased to 100 µg/L in states of
chronic inflammation. Transferrin saturation
(TSAT) levels below 20 are also diagnostic of
ID. In chronic inflammatory conditions when
ferritin levels are 100300 µg/L, TSAT should be
used to diagnose ID. Serum iron levels
fluctuate throughout the day and should not be
used for diagnosis.
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Interpretation of ferritin levels Ferritin levels
reflect body iron stores in otherwise healthy
people. However, ferritin levels are unreliable
in Acute or chronic inflammation. CKD. Heart
failure. Liver disease. Excessive alcohol
intake. Malignancy. Hyperthyroidism. In chronic
inflammatory conditionsTSAT should be used to
diagnose ID.
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Other useful tests include Hepcidin, Soluble
transferrin receptor (sTFR) and Reticulocyte
haemoglobin content (RHC) Although hepcidin is
usually low or normal in absolute ID (AID), it
helps distinguish AID from functional ID (FID)
The sTFR is a valuable indicator of ID as, unlike
ferritin, it is unaffected by inflammation.
When haemoglobin levels are normal, a low RHC
indicates early ID in functional stores and hints
at iron need, pre-anaemia and a risk of
developing IDA. The distinction between IDA and
IDWA relies on the use of strict haemoglobin
cut-offs.
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Pregnancy If iron levels need to be assessed,
the most helpful indicators are erythrocyte
protoporphyrin levels or transferrin receptors.
Ferritin levels, serum iron and transferrin are
not useful in this scenario.
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Non-anaemic Iron Deficiency management
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Patients suffering from ID should be treated
regardless of whether they are defined as
anaemic.
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NAID should be treated when identified, with a
target ferritin of 100 mg/L
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The aims of treatment are to restore red cell
indices to normal, to replace iron stores and
to treat any underlying cause.
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Where diet is a factor, nutritional advice may be
helpful. ( Regular consumption of haem iron (eg,
red meat, poultry, fish) five times a week along
with regular non-haem iron in the form of green
vegetables, etc, is recommended.)
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Iron therapy Common side-effects are nausea and
epigastric pain. These may be reduced by taking
the iron with meals or reducing the dose.
Constipation or diarrhoea may also occur. Lower
doses of ferrous sulfate may be better tolerated
and equally effective. Iron supplements taken
every few days may also be effective. Ascorbic
acid 250-500 mg twice daily, taken with the iron,
enhances absorption. Parenteral iron preparations
may be indicated where oral iron is not tolerated
or absorbed.
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Iron therapy Using single doses on alternate
days as opposed to multiple doses on consecutive
days has been shown to result in higher
absorption and better regulation of hepcidin
levels in iron-depleted women. The recommended
oral dose is 2850 mg iron daily or 100 mg on
alternate days for 25 days. Patients
haemoglobin, ferritin, and CRP levels in addition
to red blood cell indices should be checked 68
weeks following the start of treatment to assess
treatment response. Once ferritin levels have
corrected, patients should be followed up with
blood tests every 612 months, with replacement
reintroduced if necessary.
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Complications of NAID Iron depletion may cause
fatigue and reduced work performance. Iron
depletion may affect cognitive or motor
development in children. However, the evidence is
equivocal. Iron depletion may affect immune
function. Iron depletion may increase the risk of
developing heart failure, and seems to adversely
affect prognosis of existing heart failure. Iron
overload can result from excessive replacement,
and there can be a secondary haemochromatosis.
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References Non-anaemic Iron Deficiency (IDA)
(Causes, Symptoms, and Treatment) Authored by Dr
Mary Harding, Reviewed by Prof Cathy Jackson
Last edited 16 Jul 2018 Iron deficiency
without anaemia a diagnosis that
matters Abdulrahman Al-Naseem, medical student,A
Abdelrahman Sallam, medical student,A Shamim
Choudhury, medical student,A and Jecko Thachil,
consultant in haematology Clin Med (Lond). 2021
Mar 21(2) 107113.