Perioperative anaemia management

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Background

AnaemiaA reduction in the oxygen-carrying component of the blood (haemoglobin or red blood cells). is common in patients with colorectal cancer, with 30-76% of patients variably reported as anaemic at diagnosis, depending on the level of haemoglobin used to define anaemia.[1][2][3][4][5][6][7] Iron deficiency is also common in colorectal cancer and associated with poor performance and advanced disease.[8][6]

AnaemiaA reduction in the oxygen-carrying component of the blood (haemoglobin or red blood cells). is associated with adverse perioperative outcomes including increased morbidity, prolonged length of hospital stay, excessive health resource utilisation, as well as reduced disease free survival.[6][9][10][11][12][13]

Comprehensive patient blood management programs focus on preoperative correction of anaemia, in addition to other methods of minimising blood loss and improving patient care.[14][15]Back to top

Overview of evidence (non-systematic literature review)

No systematic reviews were undertaken for this topic. Practice points were based on selected published evidence. See Guidelines development process.

Perioperative treatment options for patients with anaemia

Options for correcting perioperative anemia include allogenic blood transfusion, erythropoiesis stimulating agents (ESAs) and iron supplementation in the setting of demonstrable deficiency.

Blood transfusions in the immediate perioperative period have been utilised to rectify the physiological impact of anaemia during surgery. However, the link between blood transfusion and adverse surgical outcomes, as well as increased colorectal cancer recurrence, is now well documented.[16][6][17][18]

Given the association of erythropoiesis stimulating agents with adverse outcomes, including increased thrombosis and decreased survival in cancer patients, and current prescribing restrictions, their use has been limited in colorectal cancer.[19]Back to top

Testing

Patients undergoing colorectal cancer surgery should be assessed for anaemia and iron deficiency as early as possible prior to surgery, to allow a window to correct reversible causes, in particular haematinic deficiencies, and to enable restoration of erythropoiesis.[20][21][22]

Routine blood tests should include haemoglobin, full blood count, ferritin, transferrin, transferrin saturation, B12, folate, and C-reactive protein (CRP).

The Australian National Blood Authority has easily accessible guidelines on perioperative haemoglobin assessment and optimisation, which are based on a 2010 Australian review with recommendations.[23]Back to top

Preoperative management of iron-deficiency anaemia

Therapy to correct iron deficiency anaemia should be instituted as soon as possible pre-operatively.[20][21][22]

Oral and intravenous (IV) iron have both been shown to correct iron deficiency anaemia. Four studies have evaluated the efficacy of preoperative oral iron prior to colorectal cancer surgery and have shown it to achieve reduced transfusion rates, but not a consistent increase in haemoglobin preoperatively.[24][25][26][27]

Intravenously administered iron is preferential, given the time it takes to restore iron levels orally.[28][29] IV iron also appears more effective than oral iron in correcting anaemia in gastrointestinal diseases, such as inflammatory bowel disease,[29], as well as prior to most types of surgery.[30] There is emerging evidence for its use in colorectal cancer patients.[31]

A randomised controlled trial (RCTA study in which people are allocated at random (by chance alone) to receive one of several clinical interventions. One of these interventions is the standard of comparison or control.) trial of patients undergoing resectional surgery with a preoperative diagnosis of colorectal cancer randomised 60 patients presenting with colorectal cancer to two doses of iron sucrose or placebo.[32]. Less than a third of these patients were anaemic, and the dose of intravenous iron was suboptimal, but there was a trend towards decreased transfusion among the treatment group.[32]

However, two cohort studies in anaemic colorectal cancer patients have shown an increase in haemoglobin prior to surgery and a reduced transfusion rate among patients who received IV iron.[33][34]

One RCTA study in which people are allocated at random (by chance alone) to receive one of several clinical interventions. One of these interventions is the standard of comparison or control.[35] has been recently published which randomised abdominal surgery patients with iron deficiency anaemia to standard care or IV iron carboxymaltose. Seventy per cent of these patients had colorectal cancer. Those in the IV iron group had significantly fewer transfusions, increased haemoglobin at surgery and 4 weeks post surgery, and a decreased length of stay, further supporting the role of IV iron.[35]Back to top

Postoperative management of iron-deficiency anaemia

If iron deficiency anaemia is not addressed preoperatively and/or the patients lose substantial amounts of blood during surgery, IV iron therapy should be considered after surgery.

A recent Australian study has demonstrated a pragmatic and effective approach to the management of post-operative functional iron deficiency anaemia with intravenous iron carboxymaltose in such patients.[36]

New formulations such as iron carboxymaltose can be given quickly in an outpatient or GPA medical professional who treats acute and chronic illnesses and provides preventive care and health education to a wide range of patients. setting and have rare adverse reactions, which improve their acceptability and should increase their use.[30]
Practice pointA recommendation on a subject that is outside the scope of the search strategy for the systematic review, based on expert opinion and formulated by a consensus process.Question mark transparent.png

Patients undergoing elective surgery for colorectal cancer should be assessed for anaemia and iron deficiency and any deficiencies should be addressed preoperatively.

Practice pointA recommendation on a subject that is outside the scope of the search strategy for the systematic review, based on expert opinion and formulated by a consensus process.Question mark transparent.png

Intravenous iron should be considered in preference to oral iron preoperatively given its quicker therapeutic effect.

Practice pointA recommendation on a subject that is outside the scope of the search strategy for the systematic review, based on expert opinion and formulated by a consensus process.Question mark transparent.png

Consideration should also be given to treating postoperative functional iron deficiency anaemia with intravenous iron.


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References

  1. Ludwig H, Van Belle S, Barrett-Lee P, Birgegård G, Bokemeyer C, Gascón P, et al. The European Cancer Anaemia Survey (ECAS): a large, multinational, prospective survey defining the prevalence, incidence, and treatment of anaemia in cancer patients. Eur J Cancer 2004 Oct;40(15):2293-306 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15454256.
  2. Beale AL, Penney MD, Allison MC. The prevalence of iron deficiency among patients presenting with colorectal cancer. ColorectalReferring to the large bowel, comprising the colon and rectum. Dis 2005 Jul;7(4):398-402 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15932566.
  3. Prutki M, Poljak-Blazi M, Jakopovic M, Tomas D, Stipancic I, Zarkovic N. Altered iron metabolism, transferrin receptor 1 and ferritin in patients with colon cancer. Cancer Lett 2006 Jul 18;238(2):188-96 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16111806.
  4. Kim J, Konyalian V, Huynh R, Mittal R, Stamos M, Kumar R. Identification of predictive factors for perioperative blood transfusion in colorectal resection patients. Int J ColorectalReferring to the large bowel, comprising the colon and rectum. Dis 2007 Dec;22(12):1493-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17768632.
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  13. Zhen L, Zhe S, Zhenning W, Zhifeng M, Zhidong L, Xiaoxia L, et al. Iron-deficiency anemia: a predictor of diminished disease-free survival of T3N0M0 stage colon cancer. J Surg Oncol 2012 Mar 15;105(4):371-5 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21761412.
  14. National Blood Authority. Patient Blood Management Guidelines: Module 2 Perioperative. Canberra, Australia; 2016 [cited 2016 Dec 16] Available from: https://www.blood.gov.au/pbm-module-2.
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  16. Amato A, Pescatori M. Perioperative blood transfusions for the recurrence of colorectal cancer. Cochrane Database Syst Rev 2006 Jan 25;(1):CD005033 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16437512.
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  18. Busch OR, Hop WC, Hoynck van Papendrecht MA, Marquet RL, Jeekel J. Blood transfusions and prognosis in colorectal cancer. N Engl J Med 1993 May 13;328(19):1372-6 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/8292113.
  19. Bohlius J, Schmidlin K, Brillant C, Schwarzer G, Trelle S, Seidenfeld J, et al. Erythropoietin or Darbepoetin for patients with cancer--meta-analysis based on individual patient data. Cochrane Database Syst Rev 2009 Jul 8;(3):CD007303 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19588423.
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  23. Pasricha SR, Flecknoe-Brown SC, Allen KJ, Gibson PR, McMahon LP, Olynyk JK, et al. Diagnosis and management of iron deficiency anaemia: a clinical update. Med J Aust 2010 Nov 1;193(9):525-32 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21034387.
  24. Okuyama M, Ikeda K, Shibata T, Tsukahara Y, Kitada M, Shimano T. Preoperative iron supplementation and intraoperative transfusion during colorectal cancer surgery. Surg Today 2005;35(1):36-40 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15622462.
  25. Lidder PG, Sanders G, Whitehead E, Douie WJ, Mellor N, Lewis SJ, et al. Pre-operative oral iron supplementation reduces blood transfusion in colorectal surgery - a prospective, randomised, controlled trial. Ann R Coll Surg Engl 2007 May;89(4):418-21 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17535624.
  26. Quinn M, Drummond RJ, Ross F, Murray J, Murphy J, Macdonald A. Short course pre-operative ferrous sulphate supplementation--is it worthwhile in patients with colorectal cancer? Ann R Coll Surg Engl 2010 Oct;92(7):569-72 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20573311.
  27. Ferrari P, Nicolini A, Manca ML, Rossi G, Anselmi L, Conte M, et al. Treatment of mild non-chemotherapy-induced iron deficiency anemia in cancer patients: comparison between oral ferrous bisglycinate chelate and ferrous sulfate. Biomed Pharmacother 2012 Sep;66(6):414-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22795809.
  28. Evstatiev R, Marteau P, Iqbal T, Khalif IL, Stein J, Bokemeyer B, et al. FERGIcor, a randomized controlled trial on ferric carboxymaltose for iron deficiency anemia in inflammatory bowel disease. Gastroenterology 2011 Sep;141(3):846-853.e1-2 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21699794.
  29. 29.029.1 Koduru P, Abraham BP. The role of ferric carboxymaltose in the treatment of iron deficiency anemia in patients with gastrointestinal disease. Therap Adv Gastroenterol 2016 Jan;9(1):76-85 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/26770269.
  30. 30.030.1 Auerbach M. New intravenous iron replacement therapies. Clin Adv Hematol Oncol 2010 Oct;8(10):688-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21317865.
  31. Ng O, Keeler BD, Mishra A, Simpson A, Neal K, Brookes MJ, et al. Iron therapy for pre-operative anaemia. Cochrane Database Syst Rev 2015 Dec 22;(12):CD011588 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/26694949.
  32. 32.032.1 Edwards TJ, Noble EJ, Durran A, Mellor N, Hosie KB. Randomized clinical trial of preoperative intravenous iron sucrose to reduce blood transfusion in anaemic patients after colorectal cancer surgery. Br J Surg 2009;96: 1122-8.
  33. Bisbe E, García-Erce JA, Díez-Lobo AI, Muñoz M, AnaemiaA reduction in the oxygen-carrying component of the blood (haemoglobin or red blood cells). Working Group España.. A multicentre comparative study on the efficacy of intravenous ferric carboxymaltose and iron sucrose for correcting preoperative anaemia in patients undergoing major elective surgery. Br J Anaesth 2011 Sep;107(3):477-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21841061.
  34. Keeler BD, Simpson JA, Ng S, Tselepis C, Iqbal T, Brookes MJ, et al. The feasibility and clinical efficacy of intravenous iron administration for preoperative anaemia in patients with colorectal cancer. ColorectalReferring to the large bowel, comprising the colon and rectum. Dis 2014 Oct;16(10):794-800 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/24916374.
  35. 35.035.1 Froessler B, Palm P, Weber I, Hodyl NA, Singh R, Murphy EM. The Important Role for Intravenous Iron in Perioperative Patient Blood Management in Major Abdominal Surgery: A Randomized Controlled Trial. Ann Surg 2016 Jul;264(1):41-6 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/26817624.
  36. Khalafallah AA, Yan C, Al-Badri R, Robinson E, Kirkby BE, Ingram E, et al. Intravenous ferric carboxymaltose versus standard care in the management of postoperative anaemia: a prospective, open-label, randomised controlled trial. Lancet Haematol 2016 Sep;3(9):e415-25 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/27570088.
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