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anemia of chronic inflammation

Patients with chronic systemic inflammatory disorders for more than a month usually develop mild to moderate anemia. Etiology: 1) disease states a) infection b) connective tissue disease c) malignancy d) may be associated with vitamin D deficiency [4] 2) mechanism a) defective erythropoiesis b) slightly diminished erythrocyte survival c) macrophage hyperplasia Pathology: 1) life span of erythrocytes is slightly shortened 2) bone marrow response to anemia is blunted a) inadequate secretion of erythropoietin - may be related to cytokines TNF & IL-1 b) blunted response of erythrocyte precursors to erythropoietin [3] c) iron release by macrophages is impaired by hepcidin 3) hepcidin release is increased by IL1, IL6 & interferons (inflammatory cytokines) thus down-regulating ferroportin & inhibiting export of iron from: a) duodenal enterocytes (diminished iron absorption) b) hepatocytes (diminished mobilization of hepatic stores) c) tissue macrophages (diminished iron release by bone marrow macrophages) d) increased plasma hepcidin levels in older patients may be associated with anemia of chronic inflammation [6] 4) increased synthesis of ferritin lowers serum iron Laboratory: 1) hematology a) complete blood count (CBC) - hemoglobin is low (but > 8 g/dL, 8-10 g/dL [3]) - MCV generally normal b) absolute reticulocyte count is low 2) peripheral blood a) normochromia or hypochromia b) normocytic, but may be hypochromic 3) serum chemistries a) low to low normal serum iron b) decreased total iron-binding capacity (TIBC) - < 400 ug/dL; contrast with iron deficiency anemia [3] c) iron saturation (serum iron/TIBC) > 15% - transferrin saturation may be as low as 10% [3] d) increased serum ferritin (> 35 ng/mL) e) erythropoietin levels normal, but lower than expected for degree of anemia f) serum creatinine to estimate contribution from anemia of chronic renal failure 4) bone marrow: a) stainable iron - increased stainable iron in macrophages - decreased stainable iron in erythroid precursors - overall, increased stainable iron in bone marrow b) normal erythroid maturation c) myeloid hyperplasia may be seen in chronic infections d) increased plasma cells may be seen in chronic infections Management: 1) treatment of underlying etiology generally sufficient [3] 2) since anemia is mild, transfusion is rarely needed 3) iron supplementation is NOT effective & only increases already elevated iron stores 4) erythropoietin - often relieves the anemia - however, benefit/risk ratio is unfavorable [3] - worsening hypertension - thromboembolism - increased mortality in cancer patients

Interactions

disease interactions

Related

erythropoietin (EPO) ferritin in serum/plasma iron (Fe+2/Fe+3) in serum iron-binding capacity in serum (TIBC) transferrin in serum

General

anemia of chronic disease (ACD)

References

  1. Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 573
  2. Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 1732
  3. Medical Knowledge Self Assessment Program (MKSAP) 11, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2009, 2012, 2015, 2018, 2022.
  4. Perlstein TS et al. Prevalence of 25-hydroxyvitamin D deficiency in subgroups of elderly persons with anemia: Association with anemia of inflammation. Blood 2011 Mar 10; 117:2800. PMID: 21239700
  5. Cheng PP, Jiao XY, Wang XH, Lin JH, Cai YM. Hepcidin expression in anemia of chronic disease and concomitant iron-deficiency anemia. Clin Exp Med. 2011 Mar;11(1):33-42 PMID: 20499129
  6. Ferrucci L, Semba RD, Guralnik JM et al Proinflammatory state, hepcidin, and anemia in older persons. Blood. 2010 May 6;115(18):3810-6. PMID: 20081092
  7. Wang CY, Babitt JL. Hepcidin regulation in the anemia of inflammation. Curr Opin Hematol. 2016 May;23(3):189-97. Review. PMID: 26886082 Free PMC Article
  8. Ganz T Anemia of Inflammation. N Engl J Med 2019; 381:1148-1157. Sept 19, 2019 PMID: 31532961 https://www.nejm.org/doi/full/10.1056/NEJMra1804281 - Rothaus C Anemia of Inflammation NEJM Resident 360. Sept 18, 2019 https://resident360.nejm.org/clinical-pearls/anemia-of-inflammation
  9. ARUP Consult: Anemia of Chronic Disease - Anemia of Inflammation The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/anemia-chronic-disease-anemia-inflammation - Iron Deficiency Anemia and Anemia of Chronic Disease/Anemia of Inflammation Testing Algorithm https://arupconsult.com/algorithm/iron-deficiency-anemia-and-anemia-chronic-diseaseanemia-inflammation-testing-algorithm
  10. Weiss G, Ganz T, Goodnough LT. Anemia of inflammation. Blood. 2019;133:40-50. PMID: 30401705