Perioperative anemia management in colorectal cancer patients: a pragmatic approach

Abstract

Anemia, usually due to iron deficiency, is highly prevalent among patients with colorectal cancer. Inflammatory cytokines lead to iron restricted erythropoiesis further decreasing iron availability and impairing iron utilization. Preoperative anemia predicts for decreased survival. Allogeneic blood transfusion is widely used to correct anemia and is associated with poorer surgical outcomes, increased post-operative nosocomial infections, longer hospital stays, increased rates of cancer recurrence and perioperative venous thromboembolism. Infections are more likely to occur in those with low preoperative serum ferritin level compared to those with normal levels. A multidisciplinary, multimodal, individualized strategy, collectively termed Patient Blood Management, minimizes or eliminates allogeneic blood transfusion. This includes restrictive transfusion policy, thromboprophylaxis and anemia management to improve outcomes. Normalization of preoperative hemoglobin levels is a World Health Organization recommendation. Iron repletion should be routinely ordered when indicated. Oral iron is poorly tolerated with low adherence based on published evidence. Intravenous iron is safe and effective but is frequently avoided due to misinformation and misinterpretation concerning the incidence and clinical nature of minor infusion reactions. Serious adverse events with intravenous iron are extremely rare. Newer formulations allow complete replacement dosing in 15-60 min markedly facilitating care. Erythropoiesis stimulating agents may improve response rates. A multidisciplinary, multimodal, individualized strategy, collectively termed Patient Blood Management used to minimize or eliminate allogeneic blood transfusion is indicated to improve outcomes.

Keywords: Allogeneic blood transfusion; Anemia; Colorectal cancer; Erythropoiesis stimulating agents; Intravenous iron; Patient Blood Management.

Figure 1

Pathophysiological mechanisms of anemia of inflammation in colorectal cancer. 1: Hepcidin release by colorectal cancer cells (CRC); 2,3: Decreased release of iron via ferroportin: leading to decreased transferrin-bound iron; 4: Decreased iron availability; 5: Reduced erythrocyte production; 6: Activation of immune system by CRC; 7: Release of immune and inflammatory cytokines; 8: Interleukin-6 (IL-6) induced hepcidin release; 9: Decreased erythropoietin (EPO) production; 10: Decreased erythropoietic stimulation; 11: Inhibition of erythroid cell proliferation; 12: Augmented erythrofagocytosis. IFN-γ: Interferon-γ; TNF-α: Tumor necrosis factor-α.

Figure 2

A simplified scheme of main pathways of iron metabolism. 1: Ferrireductase; 2: Divalent metal transporter (DMT1); 3: Heme protein carrier 1; 4: Ferroportin; 5: Hephastin/ceruloplasmin; 6: Transferrin receptor-1 (TfR1); 7: Several mechanisms; IL-6: Interleukin 6; RBC: Red blood cell.

Figure 3

An algorithm for anemia diagnosis. Modified from Muñoz et al[20]. ACD: Anemia of chronic disease; AUC: Anemia of unknown cause; CHr: Reticulocyte hemoglobin; CKD: Chronic kidney disease; CRP: C-reactive protein; Ft: Ferritin; Hb: Hemoglobin; ID: iron deficiency; IDA: Iron deficiency anemia; MCH: Mean corpuscular hemoglobin; MCV: Mean corpuscular volume; sTfR: Serum transferrin receptor; TSAT: Transferrin saturation; FID: Functional iron deficiency.

Figure 4

An algorithm for iron replacement. Modified from Muñoz et al[31]. FCM: Ferric caboxymaltose; Hb: Hemoglobin; LMWID: Low molecular weight iron dextran; MNF: Iron isomaltoside-1000; s: Session; TID: Total iron deficiency; CRP: C-reactive protein.