Non-Anaemic Iron Deficiency

1. Non-Anaemic Iron Deficiency
(NAID)
(Causes, Symptoms, and Treatment)
ANWER GHANI
FIBMS
IRAQ

2. 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.

3. .
 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.

4. 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.

5. Iron depletion may be three times as
common as iron deficiency anaemia
(IDA), which has a prevalence of 2-
5%.

6. 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.

7. 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 prognosis[11].

9. 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.

10. Anaemia is a late manifestation of ID

11. 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.

12. DIAGNOSIS
Serum ferritin assay has become the standard test for the
assessment of iron stores.
The WHO defines low ferritin as levels <15 μg/L for adults and <12 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 100–300 μg/L, TSAT should be
used to diagnose ID.
Serum iron levels fluctuate throughout the day and should not be used for diagnosis.

13. 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.

15. 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.

16. 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.

17. Non-anaemic Iron Deficiency
management

18. Patients suffering from ID should be
treated regardless of whether they
are defined as anaemic.

19. NAID should be treated when
identified, with a target ferritin of 100
mg/L

20. The aims of treatment are
to restore red cell indices to normal,
to replace iron stores and
to treat any underlying cause.

21. 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.)

22. 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.

23. 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 28–50 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 6–8 weeks following the start of treatment to assess treatment response.
Once ferritin levels have corrected, patients should be followed up with blood tests every 6–
12 months, with replacement reintroduced if necessary.

25. 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.

26. 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): 107–113.