Anemia of Chronic Disease

Anemia of Chronic Disease: Excerpt from The 5-Minute Pediatric Consult

Michele P. Lambert, MD

Anemia of Chronic Disease - BASICS

Anemia of Chronic Disease - description

Anemia that accompanies a variety of systemic diseases, with the common features of chronicity and inflammation. Anemia of chronic disease is also called anemia of inflammation (AI) and is the combined result of mildly increased destruction of RBCs, relative erythropoietin resistance, and iron-restricted erythropoiesis.

Anemia of Chronic Disease - pathophysiology

Associated with collagen vascular disease, inflammatory bowel disease, malignancy, severe tissue injury, renal failure, and infections

3 common pathophysiologic factors:

• Shortened red cell survival: Not seen in the anemia of all chronic disorders. The mechanism has not yet been defined.
• Impaired bone marrow erythropoietic response to the anemia, with a blunted increase in red cell production. Decreased marrow response to erythropoietin.
• Impaired iron utilization. Poor iron release from the reticuloendothelial system. This leads to a fall in plasma iron levels, a decrease in marrow sideroblasts, and a rise in red cell protoporphyrin concentration.
• Impaired erythroid progenitor response. Iron absorption may be normal or decreased. Cytokines such as interleukin-1 (IL-1) and interleukin-6 (IL-6) can activate ferritin synthesis. The ferritin can lead to sequestration of iron, which eventually is converted into hemosiderin. Recently, hepcidin has been shown to play an important role in AI. Hepcidin is increased by IL-6 and causes depletion of the only known membrane iron transporter (ferroportin) resulting in cellular inability to release stored iron and enterocyte inability to absorb iron.

Anemia of Chronic Disease - etiology

Underlying disease process

Anemia of Chronic Disease - associated conditions

• Underlying disease process:
  • Infections, both acute and chronic
  • Inflammatory disease
  • Collagen vascular diseases
  • Malignancies
  • Renal failure
• Anemia of chronic disease often coexists with other causes of anemia, including occult blood loss, hemolysis, dietary iron deficiency, and drug-related marrow suppression.

Anemia of Chronic Disease - DIAGNOSIS

Anemia of Chronic Disease - signs & symptoms

• Various abnormal physical findings may be present, depending on the underlying chronic disease process.
• May have mild pallor but will not have signs of circulatory collapse.
• Similar disease can be seen more acutely in the setting of anemia of critical illness (also part of AI).

Anemia of Chronic Disease - history

Anemia develops over the 1st month of the underlying disease process and then remains fairly stable over time.

Anemia of Chronic Disease - tests

If only the serum iron is obtained, without other iron studies, the child may be inappropriately diagnosed with iron deficiency.

Anemia of Chronic Disease - lab

• CBC with indices
• Normocytic, normochromic (can be microcytic, hypochromic when very long standing) anemia with hematocrit rarely <20%
• Reticulocyte count usually in the normal range, but low for the level of anemia
• Iron studies:
  • Low plasma iron, with low total iron-binding capacity
  • Low transferrin saturation by iron
  • Normal or high ferritin level
• Elevated free erythrocyte protoporphyrin
• Hemosiderin in bone marrow macrophages is increased if bone marrow aspiration is done and the aspirate is viewed with iron stains.
• Albumin and transferrin are both low
• Acute-phase reactants such as C-reactive protein may be elevated.

Anemia of Chronic Disease - diag proced-surgery

Bone marrow aspiration is generally not indicated.

Anemia of Chronic Disease - differencial diagnosis

Often confused with iron-deficiency anemia.

• In both iron deficiency and anemia of chronic disease:
  • Decreased plasma iron
  • Decreased transferrin saturation
  • Decreased marrow sideroblasts
  • Elevated free erythrocyte protoporphyrin
  • Decreased reticulocyte count
• In anemia of chronic disease:
  • Mild to moderate anemia
  • Mild anisocytosis
  • Usually normochromic normocytic but can be hypochromic with microcytosis
  • Decreased plasma iron
  • Decreased iron-binding capacity
  • Normal or slightly low transferrin saturation
  • Decreased marrow sideroblasts
  • Normal or elevated reticuloendothelial iron
  • Elevated free erythrocyte protoporphyrin
  • Normal or elevated ferritin
• In iron deficiency:
  • Decreased plasma iron
  • Increased iron-binding capacity
  • Decreased transferrin saturation
  • Decreased marrow sideroblasts
  • Decreased reticuloendothelial iron
  • Increased free erythrocyte protoporphyrin
  • Decreased serum ferritin

Anemia of Chronic Disease - TREATMENT

Anemia of Chronic Disease - general measures

Iron:

• Generally no role for iron therapy unless there is coexisting iron-deficiency anemia. However, recent studies in patients with renal disease have shown improved response to erythropoietin with coadministration of parenteral iron.
• Recombinant human erythropoietin:
  • Effective, but indications for use are still not universally accepted
  • Often used in chronic renal failure
  • Has been used in inflammatory bowel disease, with good results
  • Should be used for more severe and symptomatic anemia in which the underlying disease is likely to be prolonged and difficult to treat
  • May be used in childhood cancer to decrease the exposure to blood products
• Treatment should be directed at the underlying disease process.

Anemia of Chronic Disease - special therapy

Transfusion of packed RBCs is sometimes indicated intermittently in severe anemia with hemodynamic compromise.

Anemia of Chronic Disease - FOLLOW UP

Anemia of Chronic Disease - complications

If severe, patients may be transfusion dependent and thus be at risk for complications associated with packed RBC transfusions.

Anemia of Chronic Disease - patient monitoring

• Treatment of underlying disease process may promote slow resolution of associated anemia.
• Hematocrit increases ~6–8 weeks after start of recombinant human erythropoietin therapy; continues to rise over 6 months

Anemia of Chronic Disease - bibliography

Andrews NB, Bridges KC. Disorders of iron metabolism and sideroblastic anemia. In: Nathan DG, Oski FA, eds. Hematology of Infancy and Childhood. 5th ed. Philadelphia: WB Saunders; 1998:450–451.
1. Ganz T. Molecular pathogenesis of anemia of chronic disease. Pediatr Blood Cancer. 2006;46:554–557.
2. Goodnough LT, Skikne B, Brugnara C. Erythropoietin, iron, and erythropoiesis. Blood. 2000;96:823–833.
3. Means RT. Clinical application of recombinant erythropoietin in the anemia of chronic disease. Hematol Oncol Clin North Am. 1994;8:933–944.
4. Means RT. Erythropoietin in the treatment of anemia in chronic infectious, inflammatory, and malignant disease. Curr Opin Hematol. 1995;2:210–213.
Stockman JA III, Ezekowitz AB. Hematologic manifestations of systemic diseases. In: Nathan DG, Oski FA, eds. Hematology of Infancy and Childhood. 5th ed. Philadelphia: WB Saunders; 1998: 1841–1879.
5. Weiss G. Pathogenesis and treatment of anemia of chronic disease. Blood Rev. 2002;16:87–96.

Anemia of Chronic Disease - CODES

Anemia of Chronic Disease - icd9

281.9 Anemia

Anemia of Chronic Disease - FAQ

• Q: Does anemia that is associated with a chronic disease require further evaluation?
• A: If the anemia fits within the usual expectations for the patient’s diagnosis, there is no need to pursue further investigation, except in specific cases. If there is an associated malignancy for which marrow metastasis is possible, a bone marrow aspirate and biopsy should be done. In conditions with malabsorption, nutritional deficiencies and blood loss should be ruled out.

Book Source Details

• Book Title: The 5-Minute Pediatric Consult
• Author(s): M. William Schwartz MD; et al.
• Year of Publication: 2008
• Copyright Details: The 5-Minute Pediatric Consult, Copyright © 2008 Lippincott Williams & Wilkins.

More About Sickle Cell Anemia

• Back to disease: Sickle Cell Anemia: Introduction
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Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.

More About This Book: Title: The 5-Minute Pediatric Consult Authors: M. William Schwartz MD; et al. Publisher: Lippincott Williams & Wilkins Copyright: 2008 ISBN: 0-7817-7577-9

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