Identification and Treatment of Preoperative Anaemia in Adults

• Summary
• Aims
• Background
• Diagnosis and Investigation
• Treatment/Management
• Appendix 1 - Pre-operative Assessment of patients referred for major operations
• Appendix 2 - Example pathway for colorectal pre-operative anaemia pilot (50 patients)
• Appendix 3 - IV iron prescription chart

Summary of Guideline

Pre-operative iron deficiency anaemia (IDA) is the commonest cause of anaemia in the surgical population. IDA is associated with adverse outcomes following major surgery. In response to national and international guidance this guideline sets out the factors to consider when setting up a surgical specialty specific pre-operative anaemia pathway at LTHT.

IDA should be identified as early as possible in the surgical pathway by measuring full blood count and ferritin.

Once identified treatment should be commenced with oral iron if >6 weeks until surgery. If oral iron is not tolerated or <6 weeks to surgery, intravenous iron should be considered and delivered in a facility capable of administering it safely.

Each surgical specialty pathway is different so this guideline outlines the key factors to consider in order to identify and treat patients with IDA.

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Aims

To improve the diagnosis and management of pre-operative iron deficiency anaemia.

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Background

Pre-operative anaemia is associated with (grade A/B):

• Increased transfusions
• Increased length of stay
• Increased mortality
• Increased risk of kidney injury
• Increased cardiac complications
• Increased risk of infections

The above relationships hold regardless of the nature of the anaemia. Iron deficiency anaemia (IDA), which is the only readily modifiable cause for anaemia in the surgical context, happens to be the commonest cause of anaemia in surgical populations. The approach is therefore to diagnose and treat iron deficiency before surgery wherever possible.

National and international guidance recommends that patients with iron deficiency anaemia undergoing major surgery should be identified early and offered iron therapy.

NICE Guidance 24 and Quality Standard 138 recommend “people with iron-deficiency anaemia who are having surgery are offered iron supplementation before and after surgery”. International consensus (Munoz et al., 2017) recommends identifying iron deficient patients pre-operatively and commencing iron therapy either oral or intravenous. (Grade C)

This guidance will allow compliance with CQUIN CCG10: Screening and treatment of iron deficiency anaemia in patients listed for major elective blood loss surgery.

In this guideline we outline the main aspects to consider when setting up a pre-operative iron deficiency anaemia pathway.

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Diagnosis and Investigation

Patients should be identified as early as possible in the surgical pathway to allow appropriate investigation and treatment to be initiated. Early identification may require an initial FBC and ferritin at first referral to the surgeons or point of care testing in the out-patient clinic. If neither of these are possible, FBC and ferritin should be taken as soon the decision to consider surgery is made.

Key investigations include (grade C):

For every patient:

• Full blood count (FBC) - to identify presence of anaemia. Hb <130g/L (men) and <120g/L (women) suggests anaemia. These cutoffs are based on the World Health Organisation definitions of anaemia. Specialty specific data may suggest alternative cutoffs.
• Serum Ferritin - this reflects iron stores within the body. Normal serum ferritin can range from 10-322µg/L, however a serum ferritin <100µg/L is suggestive of low iron stores, with serum ferritin <30µg/L representative of iron deficiency.

Important to note: A serum ferritin >100µg/L argues against true iron deficiency; however in the setting of inflammation its diagnostic value is imperfect.  See note below regarding the potential need for use of TSAT testing to aid identification of iron deficiency in the presence of inflammation.

To be considered by each specialty:

• Transferrin saturations (TSAT) - reflects the ratio of the serum iron concentration and the total iron binding capacity expressed as a percentage. TSAT<20% suggests IDA. If there is doubt about whether there is functional iron deficiency (or a falsely high Ferritin due to inflammation) then TSAT may be useful. TSAT measurement is not routinely offered at LTHT and can take 7 to 10 days to process. Given that anaemia diagnosis and treatment need to be completed as soon as possible each specialty pathway needs to assess whether TSAT measurement should form a routine part of the pathway. Local experience suggests that TSAT measurement is required for a very small cohort (Grade D).
• C-reactive protein (CRP) - reflects presence of inflammation. Given the non-specific nature of CRP it is not an essential component of the pathway (Grade D). To ascertain whether there is a functional iron deficiency TSAT is the preferred test.

The following flow chart shows how different classes of anaemia can be identified (adapted from Munoz et al. 2017):

Whilst iron deficiency is the commonest cause in surgical patients, other types of anaemia should be investigated and treated appropriately in accordance with other guidance.

We recommend that Hb and serum ferritin measurement should be conducted at the earliest opportunity once surgery is considered (grade C).

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Treatment / Management

Once identified patients should be commenced on iron replacement therapy. The first line treatment is oral iron if there is adequate time before surgery (>6 weeks). If oral iron is not tolerated or there is <6 weeks to surgery, intravenous iron should be considered.

1. Oral iron

• Commence ferrous sulphate, fumerate or sulphate 200mg OD. If not tolerated, a reduced dose of one tablet every other day, alternative oral preparations or parenteral iron should be considered (Snook et al. 2021).

Oral iron is readily available, cheap, and safe. However, oral iron therapy takes time to be effective and after restoration of normal Hb, therapy needs to continue to replenish stores. It is therefore imperative that oral therapy is started as early in the surgical process as possible, to maximize time for it to be effective.

We recommend that oral iron therapy be started in Primary Care if possible for all patients referred for potentially major surgery, who have:

• Hb <130g/L (men) and <120g/L (women) AND serum ferritin <100ug/L
• Serum ferritin <30ug/L regardless of Hb (Grade A).

If iron deficient patients are referred “straight to test” for gastro-intestinal endoscopy, treatment should commence as soon as possible after endoscopy. The patient should receive a prescription for oral iron at referral, but postpone starting the medication until after endoscopy (Grade D).

Compliance with oral iron is often poor, especially where treatment needs to be prolonged. Furthermore, oral iron may not be sufficient where continuous iron loss occurs as part of the surgical condition (e.g. losses from GI cancer, or from severe menorrhagia), and inflammation related hepcidin release limits the absorption of enteral iron. For this reason, oral iron may prove ineffective.

2. Intravenous iron

• First line agent: Iron (III) Isomaltoside (Monofer).

This is to be prescribed using the trust approved and registered prescription chart (chart 20181123_009/RC; LTH order number LTH2889).

“Parenteral iron therapy” isn’t a single entity. The agents available vary substantially in cost, administration time (consequently nursing cost), number of visits required and incidence of adverse events. In modern agents, the iron is encapsulated in a carbohydrate shell, making the serious adverse event rates as low as 1:200 000 which is lower than with blood. These agents are thus suitable for short single-visit administration in an outpatient setting where appropriate resuscitation facilities are provided. The fact that a single visit can be effective further limits interference with surgical treatment of the primary problem.

Iron deficient patients should receive intravenous iron therapy before major surgery where they have either not responded to oral iron, or where surgery should proceed within 6 weeks from pre-assessment appointment (POA) (Grade C)- see appendix 1.

Parenteral treatment should be conducted using an agent that allows treatment with the minimum number of visits, each as short as possible, to limit postponement of surgery, nursing costs and improve the patient experience (Grade C).

Current facilities for outpatient administration are available at Wharfedale Hospital and Chapel Allerton Hospital. Further sites may need to be identified to meet demand.

An example LTHT pathway for prescription, referral and administration is detailed in Appendix 2 and 3.

Post treatment monitoring

The response to treatment should be monitored prior to surgery by measuring FBC and ferritin. If oral iron has been commenced prior to surgical referral, the bloods taken as part of the pre-operative assessment process can be used to assess response. Otherwise we recommend:

• Oral iron- response should be assessed 6 weeks after commencing treatment.
• Intravenous iron- response assessed 2-4 weeks after treatment.

The timing and results of post treatment monitoring should be considered in the context of the surgery planned and the specific patient pathway. For example, given the urgency of surgery, further treatment may not be possible if there is suboptimal response to initial treatment.

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Appendix 1

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Appendix 2 - Example pathway for colorectal pre-operative anaemia pilot (50 patients)

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Appendix 3 - IV iron prescription chart