Post‐operative erythropoiesis is limited by the inflammatory effect of surgery on iron metabolism

Abstract

The decrease in haemoglobin concentration commonly observed after major surgery is usually corrected by red cell transfusions or oral iron medication. The increased awareness of blood-transmissible diseases has led to the restrictive use of homologous blood and to interest in alternatives for correcting anaemia. We investigated the pathophysiology of postoperative anaemia by studying variables of erythropoiesis, iron metabolism, and inflammation in 48 consecutive patients who underwent total hip replacement. Haemoglobin concentration remained low during 14 days after surgery with only a mild increase in erythropoietin concentration and reticulocyte count. No increase in serum transferrin receptor concentration was observed during the first 2 weeks after surgery. Postoperative serum ferritin increased, whereas serum iron, transferrin and transferrin saturation decreased significantly. There was a marked increase in interleukin-6 and C-reactive protein with maximal values on the 1st and 4th post-operative day, respectively. At 6 weeks after surgery, haemoglobin concentration and variables of iron metabolism were almost at the preoperative level and serum transferrin receptor concentration was significantly increased, indicating increased erythropoietic activity. These changes were preceded by the normalization of interleukin-6 and C-reactive protein levels. Haemoglobin, iron, transferrin, and ferritin concentrations were not influenced by iron therapy during the postoperative period and no differences of erythropoietic and iron variables were observed between transfused and non-transfused patients. In conclusion, post-operative erythropoiesis is associated with an inflammatory effect of surgery on iron metabolism, which can explain, despite a slightly increased production of erythropoietin, the persistence of anaemia and the lack of effect of iron supplementation after surgery.

Intravenous iron and recombinant erythropoietin for the treatment of postoperative anemia

“…Studies on less severe degrees of postoperative anemia have found that correction of the anemia is slow, owing to the inflammatory effects of surgery on iron metabolism and erythropoietin response to anemia. 7,8 In the observational study by Biesma et al, which included orthopedic surgery patients without preexisting anemia (average Hb = 141 ± 11 g·L -1 ) who developed postoperative anemia with an average Hb of 111 ± 13 g·L -1 , there was no correction of anemia by one-week ) rise 10 ± 9 12 ± 6 14 ± 10 6-week Hb (g·L after surgery, while by two and six weeks after surgery there was a one-third and two-thirds correction of anemia, respectively. 8 A similar study by van Iperen et al had similar findings.…”

“…7,8 In the observational study by Biesma et al, which included orthopedic surgery patients without preexisting anemia (average Hb = 141 ± 11 g·L -1 ) who developed postoperative anemia with an average Hb of 111 ± 13 g·L -1 , there was no correction of anemia by one-week ) rise 10 ± 9 12 ± 6 14 ± 10 6-week Hb (g·L after surgery, while by two and six weeks after surgery there was a one-third and two-thirds correction of anemia, respectively. 8 A similar study by van Iperen et al had similar findings. 7 In a randomized controlled study examining treatments for postoperative anemia (see below for details of this study), Madi-Jebara et al found that, in their control group in whom the average postoperative Hb was 108 ± 13 g·L -1 , there was no correction of anemia by two-weeks after surgery, and there was only a one-third correction of anemia at four-weeks after surgery.…”

“…One is dietary iron supplementation; however, its effectiveness for this indication is, at best, minimal. 7,8,10,11 Two other therapies are iv iron therapy and recombinant erythropoietin therapy, both of which are effective in treating other types of anemia that have similar pathophysiological features to postoperative anemia, such as anemia of chronic diseases. The efficacy of these therapies in treating postoperative anemia, however, has not been appropriately assessed through randomized controlled clinical trials.…”

Preoperative Administration of Recombinant Human Erythropoietin in Patients Undergoing Gynecologic Surgery

“…Indeed, there is evidence that the characteristics of postoperative anemia are more similar to those of the anemia from chronic disease than from iron deficiency [19,20]. This kind of anemia is observed in patients with inflammatory disorders and malignancies: it is characterized by a decrease in the serum levels of iron and transferrin, by transferrin saturation despite adequate iron stores, and by a reduction in erythropoiesis [21,22].…”

Posters

“…7 Transfusion Alternatives in Transfusion Medicine VOLUME 6 NUMBER 8,9 Hence, FID is a clinical situation where the iron store in the bone marrow macrophages is normal, but this iron is not available for erythropoiesis, due to an alteration of its release from the macrophages. Also, intestinal iron absorption is inhibited, due to a reduction of its release through the enterocyte basolateral membrane.…”