Iron Deficiency Anemia And Iron-Restricted Erythropoesis (Previously Called The Anemia of Chronic Disease) – Some Resources With Excerpts

As I reviewed the two Curbsiders Anemia podcasts, Episodes #52 [Anemia – Tips And Tools For Dx And Rx] and #84 [Anemia, Iron Deficiency, IV iron, and Tony Stark], both discussed true iron deficiency (truly deficient iron stores)  and iron-restricted erythropoesis (iron stores present but unavailable for erythropoesis due to inflammation [formerly the anemia of chronic disease]).

Dr. Steensma in Episode #52 recommends

Iron deficiency anemia: Ferritin <20 suggests iron deficiency. Soluble transferrin receptor (sTfR) is inversely related to iron levels in blood. It is NOT sensitive to inflammation. High sTfR level indicates iron deficiency even if ferritin elevated.

Anemia of CKD: Hypoproliferative, normocytic (usually), and normochromic anemia. Must rule out other causes. Etiology = decreased renal erythropoietin synthesis +/- decrease RBC half life +/- absolute or functional iron deficiency (e.g. bleeding or inflammation respectively).

Anemia of Chronic Inflammation: High ferritin, low TIBC, normal serum iron, and normal or slightly high transferrin saturation (serum iron divided by TIBC). These patients rarely respond to oral iron therapy. IV iron recommended by Dr. Steensma

Dr. Auerbach, in Episode #84, states

Iron absorption and metabolism: Iron gets conjugated by acids in the stomach to vitamin C, amino acids, and sugars to protect it from the alkaline rush of the pancreas, which would turn it to ferric hydroxide (rust) and block absorption. Iron gets actively transported into cells in distal duodenum and proximal jejunum. Ferroportin exports iron from the cell into the plasma where it binds transferrin and is carried to the transferrin receptor for erythropoiesis. Excess iron gets picked up by macrophages and stored until needed. Hepcidin blocks ferroportin, which impairs iron absorption/release from gut epithelial cells and circulating macrophages (Wikipedia – Hepcidin diagram).

Iron restricted erythropoiesis: Also called functional iron deficiency, or anemia of chronic inflammation (disease). Diagnosed by normal or high serum ferritin and low transferrin saturation, generally <20%. These patients poorly absorb PO iron because of elevated hepcidin levels, but will respond to IV iron, which is directly available in the blood -Dr Auerbach.

Iron deficiency without anemia: Iron deficiency has neurologic, systemic symptoms even in absence of anemia. These patients should be treated with IV iron (Dr Auerbach’s expert opinion). Fatigue improved in patients with ferritin <15 ng/mL regardless whether or not anemia was present (Krayenbuel et al. Blood 2011)


(1) Limitations of Serum Ferritin in Diagnosing Iron Deficiency in Inflammatory Conditions [PubMed Abstract] [Full Text HTML] [Full Text PDF]. Int J Chronic Dis. 2018 Mar 18;2018:9394060. doi: 10.1155/2018/9394060. eCollection 2018.

(2) Iron deficiency or anemia of inflammation? Differential diagnosis and mechanisms of anemia of inflammation [PubMed Abstract] [Full Text HTML] [Full Text PDF]. Wien Med Wochenschr. 2016 Oct;166(13-14):411-423. Epub 2016 Aug 24

The above article has been cited 7 times in Pubmed.

(3) Treatment of Anemia of Chronic Disease with True Iron Deficiency in Pregnancy [PubMed Abstract] [Full Text HTML] [Full Text PDF]. J Pregnancy. 2017;2017:4265091. doi: 10.1155/2017/4265091. Epub 2017 Dec 4.

(4) Routine blood tests and probability of cancer in patients referred with non-specific serious symptoms: a cohort study [PubMed Abstract] [Full Text HTML] [Full Text PDF]. BMC Cancer. 2017 Dec 4;17(1):817. doi: 10.1186/s12885-017-3845-9.

(5) How I treat unexplained refractory iron deficiency anemia [PubMed Abstract] [Full Text HTML] [Full Text PDF]. Blood. 2014 Jan 16;123(3):326-33. doi: 10.1182/blood-2013-10-512624. Epub 2013 Nov 8.

(6) Detection, evaluation, and management of iron-restricted erythropoiesis [PubMed Abstract] [Full Text HTML] [Full Text PDF].  Blood. 2010 Dec 2;116(23):4754-61. doi: 10.1182/blood-2010-05-286260. Epub 2010 Sep 8.

The above article has been cited 67 times in PubMed.

(5) Case Report:Iron deficiency without anemia – a clinical challenge  [PubMed Abstract] [Full Text HTML] [Full Text PDF]. Clin Case Rep. 2018 Apr 17;6(6):1082-1086. doi: 10.1002/ccr3.1529. eCollection 2018 Jun.

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