Lawrence Tim Goodnough, MD, Professor of Pathology & Medicine, Stanford University School of Medicine, Director of Transfusion Service, Stanford University Medical Center, 300 Pasteur Dr., Room H-1402, 5626, Stanford, CA 94305, USA E-mail: Lgoodnough@stanfordmed.org
Previously undiagnosed anaemia is commonly identified during preadmission testing in patients undergoing elective surgery. Anaemia in these patients and related perioperative therapy have been associated with increased morbidity (including increased rates of perioperative infection) and mortality. Clinical care pathways for patients in these settings have been developed by the Society for Blood Management (SABM) and the Network for the Advancement of Transfusion Alternatives (NATA). These consensus recommendations emphasize the following: (1) preadmission testing, including complete blood counts (CBC) that should occur as close as possible to 30 days before the scheduled surgery date; (2) any anaemia identified should be evaluated and managed before surgery; (3) evaluations and laboratory testing should be performed to rule out nutritional causes (particularly iron deficiency), chronic kidney disease and/or anaemia of inflammation and (4) management of anaemia should include consideration of IV iron therapy and/or therapy with erythropoiesis-stimulating agents (ESA).
Previously undiagnosed anaemia is commonly identified during preadmission testing of elective surgical patients. In a national audit of patients undergoing elective orthopaedic surgery , 35% of patients were found to have haemoglobin < 13 g/dl upon preadmission testing. The large majority of such patients are women, and approximately one-third of these are the result of iron deficiency . The remainder of anaemias, although poorly characterized, are usually attributed to anaemia of chronic disease or underlying chronic kidney disease (CKD) .
Preoperative anaemia and related blood transfusion therapy have been associated with increased morbidity [4–7] and mortality  after surgery, including increased rates of perioperative infection. Gruson et al.  assessed the relationship between admission haemoglobin levels and long-term postoperative morbidity, mortality and functional recovery in an elderly population with hip fractures. This study found that patients at risk for poor outcomes could be identified by measuring haemoglobin levels at hospital admission. Dunne et al.  found a frequent incidence of preoperative anaemia in surgical patients and that blood transfusion in the first 24 h after trauma was associated with increased risk for systemic inflammatory response syndrome, intensive care admission and death. Halm et al.  recommended the diagnosis and correction of nutritional anaemia with iron, vitamin B12, folate supplementation or administration of erythropoiesis-stimulating agents (ESA). Because preoperative anaemia is associated with perioperative risks of blood transfusion, as well as increased perioperative morbidity and mortality, a standardized approach for the detection, evaluation and management of anaemia in this setting has been identified as an unmet medical need.
A panel of multidisciplinary physicians was convened by the Society for Blood Management (http://www.sabm.org) to develop a clinical care pathway for anaemia management in the elective surgical patient for whom blood transfusion is a probability (defined as any procedure for which a preoperative blood type and cross-match is requested) . The panel evaluated the current best practices with regard to screening for preoperative anaemia, anaemia evaluation and anaemia therapy. The goal of this forum was to develop a clinical care pathway for the detection, evaluation and management of anaemia in the elective surgery patient. The recommendations from this consensus development process  were as follows:
Society for Blood Management (SABM) recommendation 1
Whenever clinically feasible, elective surgical patients should have a haemoglobin level tested as close to 30 days before the scheduled surgical procedure. The Circular of Information  for blood and blood products has recommended that iron, vitamin B12, folic acid and erythropoietin be used ‘instead of blood transfusion’ if the clinical condition of the patient permits sufficient time for these agents to promote erythropoiesis, with the key phrase relevant to this recommendation being ‘sufficient time…to promote erythropoiesis’.
Based on the time interval required for anaemia evaluation and management, the panel considered a 30-day interval to be optimal in the elective surgical patient. The panel further recommended that the patient’s target haemoglobin should be within the normal range (normal woman ≥ 12 g/dl, normal man ≥ 13 g/dl) before elective surgery.
SABM recommendation 2
Unexplained anaemia should always be considered as secondary to some other process and, therefore, elective surgery should be deferred until an appropriate diagnosis is made.
To serve the patient’s best interests, efforts should be made to identify the underlying aetiologic factor or factors causing anaemia and correct or manage the condition appropriately. Clinical and functional outcomes improve with the recognition of anaemia as a symptom of an underlying condition. To facilitate this, the panel recommended that an effort be made to identify the underlying disorder causing the anaemia and to correct or manage the disorder.
A clinical care pathway (Fig. 1) was developed to provide guidance for preoperative evaluation in the elective surgical patient anticipated to have significant blood loss. Currently, limiting preadmission testing to within several days before the scheduled operative procedure precludes the opportunity to evaluate and manage the patient with unexplained anaemia. The recommended time frame of laboratory testing 30 days before the scheduled elective procedure ensures that anaemia can be detected, evaluated and managed appropriately before elective surgery.
The diagnosis of an unexplained anaemia in patients scheduled for elective surgery in which significant blood loss is anticipated should be considered an indication for rescheduling surgery until the clinical care pathway is completed. Anaemia should be viewed as a significant clinical condition, rather than simply an abnormal laboratory value . Morbidity and mortality after surgery is significantly associated with the presence of preoperative anaemia , thus warranting this recommendation. Use of the SABM clinical care pathway for anaemia management in the elective surgical patient will improve patient outcomes through the identification, evaluation and management of unexpected anaemia in this clinical setting .
More recently, the Network for the Advancement of Transfusion Alternatives (NATA) has focused on the development of practice guidelines in patients undergoing elective orthopaedic surgery. This has been particularly timely given the publication of two large, retrospective studies that have identified preoperative anaemia as predictors of postoperative morbidity and mortality for elective surgical patients [16,17z].
In a large retrospective analysis of 300 000 elderly patients undergoing non-cardiac surgery, a preoperative haematocrit of 39% or less was associated with a statistically significant increase in 30-day postoperative mortality . This finding was confirmed by a subsequent retrospective study of 8000 patients undergoing non-cardiac surgery, in which 40% of patients had preoperative anaemia, which was associated with a fivefold increase in 90-day postoperative mortality .
A multidisciplinary panel of physicians with expertise in orthopaedic surgery, orthopaedic anaesthesia, haematology and epidemiology was convened by NATA with the aim of developing practice guidelines for the detection, evaluation and management of preoperative anaemia in elective orthopaedic surgery. The Medline database was searched using the MeSH keywords ‘anemia’, ‘orthopedics’ and ‘blood transfusion’, and the abstracts of the retrieved references were reviewed to identify the relevant studies. A critical evaluation of the evidence was then performed, and recommendations were formulated according to the method proposed by the Grades of Recommendation Assessment, Development and Evaluation (GRADE) Working Group,  using the modified grading system adopted by the American College of Chest Physicians . This preliminary draft has been previously presented at the 10th Annual NATA Symposium in April 2009.
Detection of anaemia
Elective surgical patients should have an Hb level determination as close to 28 days before the scheduled surgical procedure as possible. The Circular of Information for Blood and Blood Products  has recommended that iron, vitamin B12, folic acid and erythropoietin be used instead of blood transfusion, ‘if the clinical condition of the patient permits sufficient time for those agents to promote erythropoiesis…’ The key phrase relevant to this recommendation is, ‘sufficient time…to promote erythropoiesis’. Detection of anaemia as close to 28 days before surgery is recommended for sufficient time for evaluation and management.
The patient’s target Hb before elective surgery should be within the normal range (normal woman ≥ 12 g/dl, normal man ≥ 13 g/dl), according to WHO criteria. This recommendation is a suggestion, indicating a lack of consensus on whether elective surgical procedures should be cancelled, representing best practices, for patients who are identified to be anaemic.
Evaluation of anaemia
Laboratory testing should be performed to further evaluate anaemia for nutritional deficiencies, chronic renal insufficiency and/or chronic inflammatory disease. Unexplained anaemia should be considered as secondary to some other process, [3,20], and the cause of the anaemia must be evaluated. Once the screening blood count demonstrates anaemia, evaluation begins with an assessment of iron status. When this assessment indicates absolute iron deficiency, referral to a gastroenterologist to rule out a gastrointestinal malignancy as a source of chronic blood loss is indicated .
If laboratory evaluation or a diagnostic trial of iron therapy rules out absolute iron deficiency, serum creatinine and glomerular filtration rate determination may indicate CKD and the need for referral to a nephrologist.
If ferritin and/or iron saturation values or other markers of iron-restricted erythropoiesis are indeterminant, further evaluation to rule out iron deficiency versus inflammation/chronic disease is necessary. A therapeutic trial of oral iron therapy would confirm absolute iron deficiency. No response to iron therapy may indicate: patient non-compliance ; ongoing blood (iron) losses in excess of oral iron absorption  and/or diminished gastrointestinal absorption of iron caused by inflammation . In these instances, management strategies that include intravenous iron, with or without ESA therapy, should be considered .
Management of anaemia
Nutritional deficiencies should be treated. Iron supplementation is indicated in the presence of confirmed iron-deficiency anaemia, as documented by the following laboratory values: transferrin saturation and/or serum ferritin < 30 μg/ml . Gastrointestinal evaluation for potential malignancy is recommended for any patient except possibly menstruating women .
A NATA expert panel recently reviewed the role of intravenous iron in the management of preoperative anaemia and suggested that perioperative intravenous iron should be administered perioperatively in patients undergoing orthopaedic surgery . ESA should be used for patients with anaemia in whom nutritional deficiencies have been ruled out and/or corrected.
The use of ESA therapy in patients undergoing major, elective surgery is well-established on the basis of controlled, randomized trials and is approved for use in this setting. However, recent concerns regarding the relative risk/benefit of these agents and their appropriate use in patients with CKD , in patients with anaemia related to cancer or chemotherapy  and in patients undergoing elective surgery  have resulted in categorization of the recommendation as ‘suggested’. Patients should receive iron supplementation throughout any course of ESA therapy, to optimize the dose and response relationship for ESA therapy and red-blood-cell production in the presurgical setting .
These recommendations are intended to provide guidance for preoperative evaluation in the elective surgical patient. Limiting preadmission testing to within several days before the scheduled operative procedure precludes the opportunity to evaluate and manage the patient with unexplained anaemia. The recommended time frame of testing 4 weeks before the scheduled elective procedure ensures that anaemia can be detected, evaluated and managed appropriately before elective surgery.
Anaemia should be viewed as a serious and treatable medical condition, rather than as simply an abnormal laboratory value. Anaemia is a common condition in surgical patients and is independently associated with increased mortality. The diagnosis of an unexpected anaemia in patients scheduled for elective surgery in which significant blood loss is anticipated should be considered an indication for rescheduling surgery until the evaluation is completed. The presence of preoperative anaemia is significantly associated with morbidity and mortality after surgery, thus warranting these recommendations. Implementation of anaemia management in the elective surgery setting will improve patient outcomes.