Anaemia (Iron Deficiency) V.1 - Draft

Overview

The investigation of anaemia can become quite complicated, so the BNSSG Referral Service  has developed some guidelines with the support of local gastroenterologists and haematologists to help guide further investigation.

This page is primarily concerned with the causes, investigation and treatment of iron deficiency anaemia (IDA) and non-anaemic iron deficiency (NAID)

Fpr more detailed guidance please also refer to Anaemia - iron deficiency | CKS | NICE (1) and Adult Iron Deficiency Anaemia Care Guidelines | BSG (2)

Other Remedy pages that deal with anaemia due to other causes can be found as below:

• Anaemia
• Vitamin B12
• Blood Transfusions & Iron infusions

Definitions

Anaemia is defined as haemoglobin concentration below the lower limit of normal for relevant population and laboratory performing test (1):

• In men aged over 15 years - Hb below 130 g/L.
• In non-pregnant women aged over 15 years - Hb below 120 g/L.
• In pregnant women - Hb below 110 g/L throughout pregnancy. An Hb level of 110 g/L or more appears adequate in the first trimester, and a level of 105 g/L appears adequate in the second and third trimesters.
• Postpartum - below 100 g/L.

If Hb is below the defined threshold then haematinics including ferritin should be checked.

Further advice on how to classify anaemia can be found on the Anaemia page in the haematology page - including interpretation of ferritin results.

Suspected Iron Deficiency Anaemia with normal ferritin

The important thing not to miss is an underlying iron deficiency as iron deficiency anaemia may be normocytic in some elderly patients and sometimes the ferritin is spuriously raised and so appears to be “normal”. Any inflammatory condition can falsely raise the ferritin even in the presence of iron deficiency anaemia, as can chronic kidney disease, liver disease, malignancy, hyperthyroidism and heavy alcohol intake.

To help clarify the situation, it may be worth also checking the patient’s iron status:

• NBT - available on ICE as 'iron status' under haematology panel
• UHB - there is no iron studies box to tick, so please request Transferrin saturation and Ferritin.

The finding of a low serum iron and/or low transferrin saturation would point towards an iron deficiency. Dr Charlotte Bradbury (Consultant Haematologist at BRI) has previously advised us on this and recommends the following:

'If microcytic anaemia/possible iron deficiency, it may be worth checking another marker of iron status – if transferrin saturation <20%, and ferritin <200, a trial of iron is reasonable.'

Investigation of IDA

There is no set pathway or 'one stop shop' for investigation of IDA in BNSSG. Investigations should be considered in step wise approach and will depend on various patient factors. The advice below is a general guide on what investigations may be considered.

Initial Assessment

A thorough history and examination can help to decide on the priority of investigations in primary care looking for any obvious causes of blood loss or underlying malignancy. See Assessment | Anaemia - iron deficiency | CKS for more detailed advice.

Initial tests may include:

• Bloods - FBC, haematinics, UE, LFT, coeliac screen, TFT. Consider transferrin saturation/iron studies if ferritin normal but IDA still suspected. Consider haemoglobinopathy screen if indicated.
• Urinalysis - dip for blood.

In general, investigation of IDA without any obvious cause should prioritise exclusion of lower GI causes initially.

If the diagnosis of iron deficiency anaemia is in doubt despite serum ferritin results, a diagnostic trial of oral iron treatment for 2-4 weeks may be considered in premenopausal women with a history of menorrhagia, or pregnant women (if there is no suspicion of coeliac disease). (3)

A diagnostic trial of iron treatment should not be used for men and postmenopausal women — gastrointestinal sources of bleeding need to be excluded (3).

In all patients, consider oral iron supplements which can be started prior to GI investigations (although if USC/2WW colonoscopy is requested it would be best to advise patient to not start taking the iron until the colonoscopy has been performed, but they can be given the prescription).

Lower GI Investigation

Patients over 60 with an unexplained Iron-deficiency anaemia should be referred for a colonoscopy or CT colonoscopy on USC/2WW pathway (straight to test on ICE)  - see the Lower GI - USC (2WW) for advice on appropriate investigation of patients with iron deficiency anaemia and suspected colorectal cancer.

Patients under 60 or with non-iron deficiency anaemia should initially be considered for a FIT. 

If a lower GI endoscopy outside of the USC/2WW pathway is indicated then please see the Endoscopy page,

Upper GI Investigation

Please note that iron deficiency anaemia (IDA) alone is not an indication for USC/2WW upper GI referral unless associated with other red flag symptoms - see the Upper GI - USC (2WW) page for advice.

If USC/2WW referral is not indicated and lower GI causes of anaemia have been excluded, then upper GI endoscopy outside of USC/2WW should be considered. There is no 'one stop shop' for upper and lower GI endoscopy in BNSSG and it is not recommended to refer for upper and lower GI endoscopy simultaneously.

See the Endoscopy page for details. 

Further Investigation

If a GI cause for iron deficiency anaemia is not apparent from initial upper and lower GI investigations, then please consider the following:

1. Medication - culprit drugs (e.g. NSAIDs, aspirin, anticoagulants, bisphosphonates) should be reviewed. 
2. Ensure the picture is true iron deficiency (you would be surprised how often patients are investigated in whom it isn’t true iron deficiency….)
3. Dip the urine for blood - consider urological investigations if positive. See Haematuria page.
4. Check the patient has had upper and lower GI endoscopy within the recent past (certainly within 12 months) and ensure that the quality of the endoscopic investigations are good (e.g. sometimes there is very poor bowel prep, incomplete colonoscopy etc) and consider repeating if concerned.
5. Check coeliac serology – if positive then see Coeliac disease page.

If there is still no identified cause then consider a trial of iron replacement. Monitor Hb after 1 month (Hb should rise by 1-2g/100ml over 3-4 weeks (5)) and if it drops again or fails to increment adequately with oral iron then consider referral to secondary care for consideration of small bowel investigation - see referral section below.

Non-Anaemic Iron Deficiency

The British Society of Gastroenterology Guidelines on Management of IDA (2) has advice on how to manage patients with low iron and normal Hb (page 5 or see below)

'Non-anaemic iron deficiency (NAID)

The development of anaemia from iron deficiency goes through an initial phase where body iron stores are depleted resulting in hypoferritinaemia, but the Hb concentration is still within the normal range (non-anaemic iron deficiency (NAID)). For example, in a study of young women with menorrhagia, over half had reduced iron stores but only 25% were actually anaemic.

The overall prevalence of significant underlying GI pathology, and in particular of GI malignancy, is low in NAID. In the absence of other pointers, GI investigation generally is not warranted in premenopausal women since the cause is likely to be menstrual blood loss and/or recent pregnancy (see the Special situations section).

The threshold for investigation of NAID should however be low in men, postmenopausal women, and those with GI symptoms or a family history of GI pathology'. (1)

Investigation of NAID

It is less certain who needs investigating in iron depletion without anaemia, but the following information may be relevant (4):

• Coeliac Disease is common and easily missed. Some authors state that coeliac disease may also manifest as iron depletion.

• The British Society of Gastroenterology guidelines (2) comment that, on current evidence, the prevalence of GI malignancy is low in patients with iron depletion. They suggest that, from the available evidence, the threshold for investigation should be low in the following groups: men, postmenopausal women, those with GI symptoms or a family history of GI pathology.

• Diets which are borderline low in iron are common.

• If the blood picture does not improve with treatment - eg, a trial of iron therapy - then evaluate further. 

If further investigation of NAID is considered appropriate then this should be along the lines of investigation for IDA. If there is uncertainty about the need for investigation then please consider Gastroenterology advice & guidance.

Referral

If primary care investigations as above are still not conclusive, then consider requesting Advice & Guidance or referral to gastroenterology via eRS (UHBW or NBT) for consideration of small bowel investigation.

Small Bowel Investigation

For iron-deficient anaemia, small bowel investigation is only indicated for cases that fail to correct with iron replacement (or maybe need transfusion), or sometimes when there is recurrent IDA. This is because the pathology yield from small bowel investigation is relatively low.

Proceeding directly to small bowel investigations is only indicated when there is ongoing Melaena with normal investigations – these patients tend to be under secondary care already.

The above advice is based on BSG guidelines (2) with local guidance provided by Dr Ana Terlovich (Consultant gastroenterologist at NBT).

Iron Replacement

Please see the Treatment of iron deficiency in adults document which is on the Nutrition and Blood Guidelines section of the BNSSG formulary (scroll down to bottom of page under iron). This document gives advice on treatment with oral iron and alternatives if oral iron is not tolerated or ineffective.

Dietary changes alone are usually not sufficient to correct iron deficiency anaemia (5).

If iron infusion is indicated then please see the Blood Transfusions & Iron infusions page on Remedy for advice on services available at UHBW and NBT and how to refer.

Follow up

Continue with oral iron for 3 months after normalisation of the Hb level, to ensure adequate repletion of the marrow iron stores. Recheck haemoglobin and haematinics. If iron deficiency still persisting consider referral to gastroenterology. If Hb corrected then repeat bloods 3 monthly for the first year then 6 monthly for 2-3 years. Repeat bloods again if symptoms of anaemia develop. (5)

Resources

(1) Anaemia - iron deficiency | Health topics A to Z | CKS | NICE

(2) Guidelines for the Management of Iron Deficiency Anaemia in Adults - The British Society of Gastroenterology (bsg.org.uk)

(3) Diagnostic trials of iron treatment | Diagnosis | Anaemia - iron deficiency | CKS | NICE

(4) Non-anaemic Iron Deficiency | Doctor

(5) North Central London Iron Deficiency Anaemia Pathway

Efforts are made to ensure the accuracy and agreement of these guidelines, including any content uploaded, referred to or linked to from the system. However, BNSSG ICB cannot guarantee this. This guidance does not override the individual responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or guardian or carer, in accordance with the mental capacity act, and informed by the summary of product characteristics of any drugs they are considering. Practitioners are required to perform their duties in accordance with the law and their regulators and nothing in this guidance should be interpreted in a way that would be inconsistent with compliance with those duties.

Information provided through Remedy is continually updated so please be aware any printed copies may quickly become out of date.