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Anemia of Chronic Disease

(Anemia of Chronic Inflammation)

By

Evan M. Braunstein

, MD, PhD, Johns Hopkins University School of Medicine

Last full review/revision Sep 2021
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The anemia of chronic disease is a multifactorial anemia. Diagnosis generally requires the presence of a chronic inflammatory condition, such as infection, autoimmune disease, kidney disease, or cancer. It is characterized by a microcytic or normocytic anemia and low reticulocyte count. Values for serum iron and transferrin are typically low to normal, while the serum ferritin value can be normal or elevated. Treatment is to reverse the underlying disorder and in some cases, to give erythropoietin.

Worldwide, the anemia of chronic disease is the 2nd most common anemia. Early on, the red blood cells (RBCs) are normocytic; with time they may become microcytic. The major issue is that erythropoiesis is restricted due to inappropriate iron sequestration.

Etiology of Anemia of Chronic Disease

Three pathophysiologic mechanisms have been identified:

  • Slightly shortened RBC survival, thought to be due to increased hemophagocytosis by macrophages, occurs in patients with inflammatory diseases.

  • Erythropoiesis is impaired because of decreases in both erythropoietin (EPO) production and marrow responsiveness to EPO.

  • Iron metabolism is altered due to an increase in hepcidin, which inhibits iron absorption and recycling, leading to iron sequestration.

Reticuloendothelial cells retain iron from senescent RBCs, making iron unavailable for hemoglobin (Hb) synthesis. There is thus a failure to compensate for the anemia with increased RBC production. Macrophage-derived cytokines (eg, interleukin-1-beta, tumor necrosis factor-alpha, interferon-beta) in patients with infections, inflammatory states, and cancer contribute to the decrease in EPO production and impaired iron availability by increased hepatic hepcidin synthesis.

Diagnosis of Anemia of Chronic Disease

  • Symptoms and signs of the underlying disorder

  • Complete blood count (CBC) and serum iron, ferritin, transferrin, and reticulocyte count

Clinical findings in the anemia of chronic disease are usually those of the underlying disorder (infection, inflammation, cancer). The anemia of chronic disease should be suspected in patients with microcytic or normocytic anemia who also have chronic illness, infection, inflammation, or cancer. If anemia of chronic disease is suspected, serum iron, transferrin, reticulocyte count and serum ferritin are measured. Hb usually is > 8 g/dL (> 80 g/L) unless an additional mechanism contributes to anemia, such as concomitant iron deficiency (see table Differential Diagnosis of Microcytic Anemia Due to Decreased RBC Production Differential Diagnosis of Microcytic Anemia Due to Decreased Red Blood Cell Production Iron deficiency is the most common cause of anemia and usually results from blood loss; malabsorption, such as with celiac disease, is a much less common cause. Symptoms are usually nonspecific... read more Differential Diagnosis of Microcytic Anemia Due to Decreased Red Blood Cell Production ) or iatrogenic phlebotomy.

A serum ferritin level of < 100 ng/mL (< 224.7 pmol/L) in a patient with inflammation (< 200 ng/mL [< 449.4 pmol/L] in patients with chronic kidney disease Chronic Kidney Disease Chronic kidney disease (CKD) is long-standing, progressive deterioration of renal function. Symptoms develop slowly and in advanced stages include anorexia, nausea, vomiting, stomatitis, dysgeusia... read more Chronic Kidney Disease ) suggests that iron deficiency may be superimposed on anemia of chronic disease, because serum ferritin is usually elevated as an acute-phase reactant.

Treatment of Anemia of Chronic Disease

  • Treatment of underlying disorder

  • Sometimes iron supplements

Treatment of the anemia of chronic disease requires treating the underlying disorder. Because the anemia is generally mild, transfusions usually are not required.

Iron supplementation may be helpful because iron deficiency Overview of Acute Viral Hepatitis Acute viral hepatitis is diffuse liver inflammation caused by specific hepatotropic viruses that have diverse modes of transmission and epidemiologies. A nonspecific viral prodrome is followed... read more can occur in patients with anemia of chronic disease, and iron studies are often difficult to interpret when these conditions coexist.

Key Points

  • Almost any chronic infection, inflammation, or cancer can cause anemia; hemoglobin usually is > 8 g/dL (> 80 g/L) unless an additional mechanism contributes.

  • Multiple factors are involved, including shortened red blood cell survival, impaired erythropoiesis, and impaired iron availability.

  • Anemia is initially normocytic and then can become microcytic.

  • Serum iron and transferrin are typically decreased, while ferritin is normal to increased.

  • Treat the underlying disorder.

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