4.2: Anemia of Chronic Inflammation/Disease (ACI/ACD)

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Cause(s):

Anemia that occurs in patients with conditions that result in chronic inflammatory states such as rheumatoid arthritis, infections, and malignancies. Anemia is reversed when underlying condition is treated and inflammation subsides.¹ Chronic inflammation leads to an increase in inflammatory cytokines and actue phase reactants that alter iron metabolism and decrease RBC production and lifespan.

Additional notes:

Acute phase reactants are serum proteins whose levels are increased by the liver in response to inflammation. Three related acute phase reactants to ACI are:²

Hepcidin
Lactoferrin
Ferritin

Mechanisms of anemia development in ACI:^1,3

Decrease in iron available for erythropoiesis (increased hepcidin causes inhibition of iron release from macrophages and decreased iron absorption from the diet, iron bound to lactoferrin and ferritin is not available to developing RBCs)
EPO production in the kidneys is inhibited by cytokines
Erythropoiesis is inhibited by cytokines (diminishes developing erythroid precursor’s response to EPO)
Decreased RBC survival (increased activation of macrophages by inflammatory cytokines leads to increased removal of RBCs from circulation and decreased survival)

Laboratory Features:^1,2,4

CBC:

RBC: Decreased

WBC: Normal or Increased depending on the cause of the inflammation

PLT: Normal

Hb: Decreased

Hct: Normal to Decreased

MCV, MCH, MCHC: Normal to Decreased

RDW: Increased

PBS:

Normochromic, Normocytic OR Microcytic, hypochromic RBCs

BM:

M:E Ratio: Increased

(Decreased production of erythroids, +/- increased production of myeloids)

Iron Stores: Increased

Iron Studies:

Serum Iron: Decreased

Ferritin: Increased

Transferrin: Decreased

Transferrin saturation: Normal to Decreased

TIBC: Decreased

Other Tests:

N/A

References:

1. McKenzie SB. Anemias of disordered iron metabolism and heme synthesis. In: Clinical laboratory hematology. 3rd ed. New Jersey: Pearson; 2015. p. 198-230.

2. Doig K. Disorders of iron kinetics and heme metabolism. In: Rodak’s hematology clinical applications and principles. 5th ed. St. Louis, Missouri: Saunders; 2015. p. 297-313.

3. Turgeon ML. Hypochromic anemias and disorders of iron metabolism. In: Clinical hematology: theory and procedures. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 1999. p. 131-144.

4. Finnegan K. Iron metabolism and hypochromic anemias. In: Clinical hematology and fundamentals of hemostasis. 5th ed. Philadelphia: F.A. Davis Company; 2009. p. 117-37.