Preoperative anaemia has been identified as a marker for poor postoperative outcome. Almost a third of the general population is anaemic, and this is more prevalent in the elderly. However preoperative anaemia can affect up to 75% of the surgical population depending on comorbidity, gender, age and underlying pathology necessitating surgery. Timely identification and treatment of preoperative anaemia is advocated to minimise requirements for blood transfusion, and transfusion-associated adverse outcomes and aid patient recovery. This can provide significant cost savings that is beneficial for patients, with improved clinical outcomes, reduced length of hospital stay and also a reduction in the use of blood products. (Munoz 2015).

Patient Blood Management (PBM) is an evidence-based, multidisciplinary team approach to optimising the care of patient who may require a blood transfusion. It focuses on measures for blood avoidance as well as correct use of blood components when they are needed. Preventive strategies are emphasized to identify, evaluate, and manage anaemia. Management of Preoperative Anaemia (MoPA) provides a preventive strategy to identify, evaluate and manage anaemia for patients undergoing major surgery, including pathways for elective and urgent surgery which is embraced by Perioperative Medicine (RCOA) in conjunction with NICE guidance (Spahn 2012).

• To identify and optimise all patients with anaemia prior to major surgery to minimise the risk of requiring an allogeneic blood transfusion.
• To provide healthcare professionals with clear recommendations for the management of anaemia prior to major surgery including iron replacement therapy (both oral and intravenous iron).
• To reduce blood usage related to surgery.

Major surgery – estimated blood loss of >10% of circulating blood volume and/or estimated blood loss of >500ml.

The following surgical procedures in Ayrshire & Arran should be considered;

General surgery:  

• • Colorectal resection for any indication (open or laparoscopic)

Vascular: 

• • Open arterial surgery, scheduled (non-ruptured) aortic aneurysm repair, infrainguinal femuropopliteal or distal bypass.

Orthopaedics: 

• • Primary or revision total hip replacement.
  • Primary or revision total knee replacement.

Urology: 

• • Nephrectomy
  • Cystectomy

        Gynaecology:

• • Simple or complex hysterectomy.

Anaemia before major surgery - Hb <130 g/L for both men and women

• This is the trigger threshold for investigation and treatment when preparing for major surgery where significant blood loss may be anticipated.
  • This differs from WHO definition of Hb <130g/L for men and Hb <120g/L for women.
  • Females have a lower circulating blood volume, and therefore any blood loss is a relatively higher percentage of total blood volume compared with males, and hence will result in a more significant impact on circulating haemoglobin.
  • Patients must not be transfused to achieve this target.

The cause of anaemia may be multifactorial.

Iron deficiency may be a contributing factor due to:

• decreased iron in diet
• impaired iron absorption
• iron sequestration syndrome due to inflammatory conditions
• chronic blood loss.

Diagnosis and management of peri-operative anaemia in surgical patients

• Functional iron deficiency – insufficient mobilisation from iron stores in the presence of increased demands
  • Ferritin <100 mcg/ml* or
  • Ferritin 100-300 mcg/ml AND
  • Transferrin saturation (TSATS) <20%

* Ferritin is an acute phase protein and may be raised in the presence of inflammation or infection and should be considered in conjunction with CRP)

• Absolute iron deficiency - iron stores are inadequate to support erthropoietic needs of the bone marrow
  • Ferritin <30 mcg/ml
  • Transferrin saturation (TSATS <20%)

Absolute iron deficiency requires investigation, particularly in patients without a clear physiological explanation for iron deficiency including chronic kidney disease or occult malignancy. It is recommended that adult men and postmenopausal women (and premenopausal women with GI symptoms) be referred for gastroscopy/colonoscopy to exclude a source of bleeding unless there is an overt non-gastrointestinal cause.

Patients who are not anaemic, but with evidence of iron deficiency undergoing surgery with a high risk of developing anaemia, will also benefit from iron therapy to improve recovery. However this is not an indicator to delay surgery.

Oral iron formulations

• Oral iron replacement should initiated as soon as possible in the preoperative pathway in patients with iron deficiency anaemia, ideally at least scheduled 6-8 weeks before surgery. 
• Patients identified to have a functional iron deficiency who are not anaemic will benefit from iron replacement therapy.
• Haemoglobin levels should rise by 10-15g/L in 4 weeks of oral iron treatment.
• A patient guided directive (PGD) for oral iron has been created to dispense oral iron from the preoperative assessment clinic. Administration of oral iron can be once daily rather than previous guidance of taking oral iron three times daily. This will minimise side effects and improve compliance.

Intravenous iron therapy

• Absorption of oral iron is inhibited in the presence of hepcidin (a protein which is produced by the liver in a chronic inflammatory state). This blocks the uptake of iron from the gut. Intravenous iron bypasses the problems encountered with enteral absorption.
• Intravenous iron replenishes stores in preparation for the accelerated erythropoiesis seen following blood loss in major surgery.
• Intravenous iron is indicated in patients who;
  • do not respond to oral iron or are unable to tolerate it;
  • if surgery is planned for < 6 weeks after the diagnosis of iron deficiency.
• Intravenous iron should ideally be given 4-6 weeks before surgery.
• Due to the limited time frame before surgery, the highest allowable dose of intravenous iron should be utilised.
• If surgery is urgent surgery, it should be considered up to and including on the day of surgery as this will still reduce the need for perioperative transfusion.
• Historically intravenous iron has been associated with a risk of anaphylaxis, however more recent formulations are much safer and efficacious.
• Administration of parenteral iron may occur as an outpatient procedure, dependent on the local pathway for each hospital, however it requires a facility with full resuscitation facilities.
• The dosage calculation and administration, and relative contraindications are detailed in the Guideline for the use of intravenous iron for the treatment of iron deficiency anaemia ADTC 279.  The optimal formulation and dosing regimen should be employed to minimise the requirement for more than one iron infusion due to limited time before surgery.

Erythropoietin for the correction of anaemia is outwith the remit of this guideline.

See the Management algorithm for patient with iron deficiency anaemia.

• Screening for anaemia should commence as early as possible in the referral pathway to allow sufficient time for investigation and correction if appropriate. Ideally when patients are referred from primary care, they should have modifiable risk factors addressed including screening and treatment of anaemia.
• When the patient is booked for major surgery at the surgical outpatient clinic, or through endoscopy, screening bloods for anaemia are to be taken.
  • These include FBC, U&E, and CRP.

(* If the laboratory allows automatic ordering, these further investigations may be added if Hb <130g/L is detected on a routine sampling for major surgery)

• • All blood results should be reviewed within 2-3 working days by preoperative nursing staff.
    • If the Hb <130g/L, then iron studies* (TSAT, serum ferritin) haemotinics* (B12, folate) will be added to the request.
    • If a haemoglobin of <130 g/L is detected, the patient is to be commenced appropriate treatment (iron, B12 or folate), depending on the urgency of surgery. Patient guided directives (PGDs) have been created for oral iron and folate. 
    • Abnormal results should be discussed with the Lead Clinical Team, or the preoperative assessment anaesthetist.
    • Referral for further investigation is required if there is evidence of absolute iron deficiency, which is the responsibility of the Lead Clinical Team. It should not be referred back to primary care to organise further investigations. National guideline for B12 and Folate Deficiency
  • Major, non-urgent surgery should be postponed to allow for investigation of and treatment of anaemia, notably iron deficiency.
• If surgery is elective, and there is evidence of iron deficiency, patients will be instructed to commence oral iron therapy, dispensed from the Preoperative Assessment Clinic utilising a PGD. They will be reviewed in the Preoperative Assessment Clinic approximately 6 weeks later whereby further blood tests will be taken assess if they have responded to oral iron therapy.  If they remain anaemic despite oral iron therapy, or have not been able to tolerate oral iron, patients will then require intravenous iron therapy.
• If surgery is urgent (< 6 weeks until scheduled date), the patient should be treated with intravenous iron therapy. This should be prescribed by the Lead Clinical Team, or in discussion with appropriate anaesthetist).
• All patients who are taking anticoagulant drugs such as warfarin, aspirin or other anti-platelet agents (e.g. dipyridamole or clopidogrel, NSAIDs or DOACs) should be identified and necessary arrangements made to stop the drug preoperatively as part of patient blood management (PBM). See Perioperative management of the patient on oral anticoagulants and antiplatelet agents ADTC117
• Inherited haemoglobin disorders (haemoglobinopathies) should be considered in all individuals with microcytic anaemia if there is no evidence of iron deficiency anaemia, or if red cell changes persist after adequate after adequate iron replacement.

• Anaemia should be treated prior to surgery, depending on the urgency of the operation. On the day of surgery a FBC should be repeated, and Group and Screen or Cross match must be performed in accordance with the MSBOS (Maximum Surgical Blood Ordering Schedule) for the specific procedure, and consideration of electronic blood issue.
• Intraoperative and postoperative care should consider additional management strategies in line with guidance from PBM, including the use of tranexamic acid, cell salvage, and restrictive transfusion policies).

• Consider clinical indications and transfusion triggers before giving a blood transfusion. If patient blood management measures did not prevent the development of severe postoperative anaemia, the adoption of a restrictive transfusion threshold (Hb 70–80 g/L, depending on patient comorbidities) is recommended in most adult, clinically stable patients.
• However in conjunction with restrictive transfusion policy postoperatively, patients with moderate-severe anaemia (Hb <100 g/L), or high blood loss during surgery, should be treated with intravenous iron replacement therapy. Absorption of oral iron in the postoperative period will be inhibited due to the pro-inflammatory state induced by surgery and make oral iron therapy largely ineffective. Therefore intravenous iron should be utilised with a single high-dose intravenous preparation rather than prescribing oral iron for discharge in the first few weeks after surgery.

• MoPA compliance will be monitored as part of the PBM quality improvement work stream, and regularly fed back to key stakeholders. This is part of the National Modernising Patient Pathway Process (MPPP) from the Scottish Government.
• This includes: haemoglobin at the time of surgery; treatment methods of iron deficiency; blood transfusion thresholds; identification of underlying disease.

Referenced guidelines for Ayrshire and Arran

• Guideline for the use of intravenous iron for the treatment of iron deficiency anaemia (ADTC 279) http://athena/adtc/DTC%20%20Clinical%20Guidelines/ADTC279.pdf
•  Perioperative management of the patient on oral anticoagulants and antiplatelet agents (ADTC117) http://athena/adtc/DTC%20%20Clinical%20Guidelines/ADTC117.pdf
• British Committee for Standards in Haematology - National guideline for B12 and Folate Deficiency http://athena/adtc/DTC%20%20Clinical%20Guidelines/BCSH%20Guideline%20for%20B12%20and%20Folate%20Deficiency.pdf

References / Bibliography

Beris P, Munoz M, Gardia-Erce et al. Perioperative anaemia management: consensus statement on the role of intravenous iron.  British Journal of Anaesthesia 2008;100: 599-604

Goodnough L, Maniatis A, Earnshaw P et al  Detection, evaluation, and management of preoperative anaemia in the elective orthopaedic surgical patient: NATA guidelines  British Journal of Anaesthesia 2012;106:12-22National Blood Authority. Patient Blood Management Guidelines: Module 2 – Peri-operative. https://www.blood.gov.au/pbm-module-2

NICE guidance Blood transfusion Quality standard [QS138] December 2016. Available from:https://www.nice.org.uk/guidance/qs138/chapter/quality-statement-1-iron-supplementation

NICE guidance 180 Perioperative care in adults Evidence review for preoperative management of anaemia August 2020. Available from:https://www.nice.org.uk/guidance/ng180/evidence/e-preoperative-management-of-anaemia-pdf-8833151058

Munoz M, Acheson AG, Aurerbach M et al International Consensus statement on the perio-operative management of anaemia and iron deficiency.  Anesthesia 2017;72: 233-247

Munoz M, Acheson AG, Bisbe E et al International Consensus statement on the management of posterative anaemia after major surgical procedures.  Anaesthesia 2018; 73:1418–1431

Munoz M, Gomez-Ramirez S, Kozek-Langeneker S et al ‘Fit to fly’: overcoming barriers to preoperative haemoblogin optimization in surgical patients. British Journal of Anaesthesia 2015; 115: 15-24

Spahn DR, Goodnough LT. Alternatives to blood transfusion. Lancet 2013;381:1855–1865