Colorectal cancer

Perioperative anaemia management

From Cancer Guidelines Wiki

Background[edit source]

Anaemia 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]

Anaemia 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]

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Overview of evidence (non-systematic literature review)[edit source]

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[edit source]

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]

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Testing[edit source]

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]

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Preoperative management of iron-deficiency anaemia[edit source]

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 (RCT) 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 RCT[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]

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Postoperative management of iron-deficiency anaemia[edit source]

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 GP setting and have rare adverse reactions, which improve their acceptability and should increase their use.[30]

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

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

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

Next section: Thromboembolic prophylaxis

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References[edit source]

  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 Available from:
  2. Beale AL, Penney MD, Allison MC. The prevalence of iron deficiency among patients presenting with colorectal cancer. Colorectal Dis 2005 Jul;7(4):398-402 Available from:
  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 Available from:
  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 Colorectal Dis 2007 Dec;22(12):1493-7 Available from:
  5. Hamilton W, Lancashire R, Sharp D, Peters TJ, Cheng KK, Marshall T. The importance of anaemia in diagnosing colorectal cancer: a case-control study using electronic primary care records. Br J Cancer 2008 Jan 29;98(2):323-7 Available from:
  6. 6.0 6.1 6.2 6.3 Acheson AG, Brookes MJ, Spahn DR. Effects of allogeneic red blood cell transfusions on clinical outcomes in patients undergoing colorectal cancer surgery: a systematic review and meta-analysis. Ann Surg 2012 Aug;256(2):235-44 Available from:
  7. Edna TH, Karlsen V, Jullumstrø E, Lydersen S. Prevalence of anaemia at diagnosis of colorectal cancer: assessment of associated risk factors. Hepatogastroenterology 2012 May;59(115):713-6 Available from:
  8. Prades J, Remue E, van Hoof E, Borras JM. Is it worth reorganising cancer services on the basis of multidisciplinary teams (MDTs)? A systematic review of the objectives and organisation of MDTs and their impact on patient outcomes. Health Policy 2015 Apr;119(4):464-74 Available from:
  9. Ludwig H, Müldür E, Endler G, Hübl W. Prevalence of iron deficiency across different tumors and its association with poor performance status, disease status and anemia. Ann Oncol 2013 Jul;24(7):1886-92 Available from:
  10. Leichtle SW, Mouawad NJ, Lampman R, Singal B, Cleary RK. Does preoperative anemia adversely affect colon and rectal surgery outcomes? J Am Coll Surg 2011 Feb;212(2):187-94 Available from:
  11. Musallam KM, Tamim HM, Richards T, Spahn DR, Rosendaal FR, Habbal A, et al. Preoperative anaemia and postoperative outcomes in non-cardiac surgery: a retrospective cohort study. Lancet 2011 Oct 15;378(9800):1396-407 Available from:
  12. Kang CY, Chaudhry OO, Halabi WJ, Nguyen V, Carmichael JC, Mills S, et al. Risk factors for postoperative urinary tract infection and urinary retention in patients undergoing surgery for colorectal cancer. Am Surg 2012 Oct;78(10):1100-4 Available from:
  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 Available from:
  14. National Blood Authority. Patient Blood Management Guidelines: Module 2 Perioperative. Canberra, Australia; 2016 [cited 2016 Dec 16] Available from:
  15. Clevenger B, Mallett SV, Klein AA, Richards T. Patient blood management to reduce surgical risk. Br J Surg 2015 Oct;102(11):1325-37; discussion 1324 Available from:
  16. Amato A, Pescatori M. Perioperative blood transfusions for the recurrence of colorectal cancer. Cochrane Database Syst Rev 2006 Jan 25;(1):CD005033 Available from:
  17. von Bormann B, Suksompong S, Schleinzer W. Blood transfusions and prognosis in colorectal cancer: long-term results of a randomized controlled trial. Ann Surg 2015 May;261(5):e136 Available from:
  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 Available from:
  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 Available from:
  20. 20.0 20.1 Froessler B, Papendorf D. Intravenous iron sucrose--an effective and attractive modality for perioperative anaemia management. Anaesth Intensive Care 2010 Sep;38(5):960-2 Available from:
  21. 21.0 21.1 Muñoz M, Gómez-Ramírez S, Martín-Montañez E, Auerbach M. Perioperative anemia management in colorectal cancer patients: a pragmatic approach. World J Gastroenterol 2014 Feb 28;20(8):1972-85 Available from:
  22. 22.0 22.1 Muñoz M, Gómez-Ramírez S, Campos A, Ruiz J, Liumbruno GM. Pre-operative anaemia: prevalence, consequences and approaches to management. Blood Transfus 2015 Jul;13(3):370-9 Available from:
  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 Available from:
  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 Available from:
  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 Available from:
  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 Available from:
  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 Available from:
  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 Available from:
  29. 29.0 29.1 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 Available from:
  30. 30.0 30.1 Auerbach M. New intravenous iron replacement therapies. Clin Adv Hematol Oncol 2010 Oct;8(10):688-9 Available from:
  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 Available from:
  32. 32.0 32.1 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, Anaemia 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 Available from:
  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. Colorectal Dis 2014 Oct;16(10):794-800 Available from:
  35. 35.0 35.1 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 Available from:
  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 Available from:

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