anemia of chronic inflammation
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Introduction
Patients with chronic systemic inflammatory disorders for more than a month usually develop mild to moderate anemia.
Etiology
- disease states
- infection
- connective tissue disease
- malignancy
- may be associated with vitamin D deficiency[4]
- mechanism
- defective erythropoiesis
- slightly diminished erythrocyte survival
- macrophage hyperplasia
Pathology
- life span of erythrocytes is slightly shortened
- bone marrow response to anemia is blunted
- inadequate secretion of erythropoietin
- blunted response of erythrocyte precursors to erythropoietin[3]
- iron release by macrophages is impaired by hepcidin
- hepcidin release is increased by IL1, IL6 & interferons (inflammatory cytokines) thus down-regulating ferroportin & inhibiting export of iron from:
- duodenal enterocytes (diminished iron absorption)
- hepatocytes (diminished mobilization of hepatic stores)
- tissue macrophages (diminished iron release by bone marrow macrophages)
- increased plasma hepcidin levels in older patients may be associated with anemia of chronic inflammation[6]
- increased synthesis of ferritin lowers serum iron
Laboratory
- hematology
- complete blood count (CBC)
- hemoglobin is low (but > 8 g/dL, 8-10 g/dL[3])
- MCV generally normal
- absolute reticulocyte count is low
- complete blood count (CBC)
- peripheral blood
- normochromia or hypochromia
- normocytic, but may be hypochromic
- serum chemistries
- low to low normal serum iron
- decreased total iron-binding capacity (TIBC)
- < 400 ug/dL; contrast with iron deficiency anemia[3]
- iron saturation (serum iron/TIBC) > 15%
- transferrin saturation may be as low as 10%[3]
- increased serum ferritin (> 35 ng/mL)
- erythropoietin levels normal, but lower than expected for degree of anemia
- serum creatinine to estimate contribution from anemia of chronic renal failure
- bone marrow:
- stainable iron
- increased stainable iron in macrophages
- decreased stainable iron in erythroid precursors
- overall, increased stainable iron in bone marrow
- normal erythroid maturation
- myeloid hyperplasia may be seen in chronic infections
- increased plasma cells may be seen in chronic infections
- stainable iron
Management
- treatment of underlying etiology generally sufficient[3]
- since anemia is mild, transfusion is rarely needed
- iron supplementation is NOT effective & only increases already elevated iron stores
- erythropoietin
- often relieves the anemia
- however, benefit/risk ratio is unfavorable[3]
- worsening hypertension
- thromboembolism
- increased mortality in cancer patients
More general terms
Additional terms
- erythropoietin (EPO)
- ferritin in serum/plasma
- iron (Fe+2/Fe+3) in serum
- iron-binding capacity in serum (TIBC)
- transferrin in serum
References
- ↑ Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 573
- ↑ Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 1732
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 Medical Knowledge Self Assessment Program (MKSAP) 11, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2009, 2012, 2015, 2018, 2022.
- ↑ 4.0 4.1 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: https://www.ncbi.nlm.nih.gov/pubmed/21239700
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/20499129
- ↑ 6.0 6.1 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: https://www.ncbi.nlm.nih.gov/pubmed/20081092
- ↑ Wang CY, Babitt JL. Hepcidin regulation in the anemia of inflammation. Curr Opin Hematol. 2016 May;23(3):189-97. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/26886082 Free PMC Article
- ↑ Ganz T Anemia of Inflammation. N Engl J Med 2019; 381:1148-1157. Sept 19, 2019 PMID: https://www.ncbi.nlm.nih.gov/pubmed/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 - ↑ 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 - ↑ Weiss G, Ganz T, Goodnough LT. Anemia of inflammation. Blood. 2019;133:40-50. PMID: https://www.ncbi.nlm.nih.gov/pubmed/30401705