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Anaemia of Chronic Illness: Causes and Pathophysiology

  • 3 minutes, 34 seconds
  • Hematology
  • 2020-07-04 19:36:53

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Anaemia of chronic illness is a common complication of chronic infections, inflammation, and cancer. This type of anaemia is the second most prevalent cause of anaemia, after iron deficiency anaemia which is the leading.

This anaemia of chronic illness is usually encountered in individuals in whom their current disease state causes an active immune response or an inflammatory response leading to reduced iron uptake at varying sites. This is not the cass in patients in whose illness or treatment directly causes anaemia as is like in some cancers and the use of cytotoxic drugs .

It is observed as a mild to moderate anaemia in patients diagnosed with other chronic disease diseases, which may not be of purely inflammatory response.

This state is seen in several diseases such as malignancies, chronic infections and auto-immune diseases , thereby indicating the multiplicity in pathogenetic pathways that may lead to anaemia of chronic illness.

The most common causes of chronic disease anemias are;

  1. Acute and chronic infections such as HIV/AIDS and osteomyelitis;
  2. Cancers; (haematological, solid tumour)
  3. Autoimmune disorders such as rheumatoid arthritis,systemic lupus erythematosus, and inflammatory bowel disease,vasculitis, sarcoidosis;
  4. Chronic kidney disease.
  5. Chronic rejection after solid-organ transplantation

The pathogenetic processes involved reflect the active protection expressed by an effective immune system in depriving the invading cells of iron, which is an important nutrient for the proliferation of both cancer cells and pathogens.

These processes primarily include bone marrow invasion by tumours or infective agents, alteration of iron metabolism and diversion of body iron, haemophagocytosis, reduction in erythropoiesis, and diminished response to erythropoietin stimulation .

The pathogenetic processes are thought to be mediated through the actions of tumour necrosis factor (TNF) and interleukins (IL)-1 and −6, and interferon (IFN) . These cytokines, as well as the acute-phase protein hepcidin, are believed to inhibit iron release from the marrow macrophages to the budding erythroid progenitors.

The cytokines also directly induce the modulation of translation/transcriptions of genes involved in iron homeostasis, either directly or via production of labile radicals.

Anaemia of chronic illness vs iron deficiency anaemia

Anaemia of chronic illness(ACI) is the most common form of anaemia in hospitalized patients. It resembles the anaemia of iron deficiency, but it stems from inflammation-induced sequestration of iron within the cells of the mononuclear phagocyte (reticuloendothelial) system.

The serum iron levels are usually low, and the red cells can be normocytic and normochromic, or, as in anaemia of iron deficiency, hypochromic and microcytic

It is important to rule out iron deficiency and other causes of anaemia.

Anaemia of chronic disease is associated with;

  • Increased storage iron in the bone marrow,
  • High serum ferritin concentration, and
  • Reduced total iron-binding capacity,

All of these characteristics readily rule out iron deficiency.


The pathogenetic mechanisms vary depending on the cause. However, each of the individual factors plays some role in the eventual cause of anaemia. Here below is an overview of the mechanisms involved.

  1. Iron Dysregulation/Reticulo-Endothelial Iron Block,
  2. Reduced Erythropoiesis,
  3. Diminished Response to Erythropoietin,
  4. Hypoferraemia and Reduced Erythrocyte Survival,
  5. Bone Marrow Infiltration.

High concentrations of circulating hepcidin, which inhibits ferroportin and thereby block the transfer of iron from the mononuclear phagocyte storage pool to the erythroid precursors.

The elevated hepcidin concentrations are caused by pro-inflammatory cytokines, which enhance the synthesis of hepcidin by the liver.

In addition, chronic inflammation also blunts the compensatory increase in erythropoietin levels, which is not adequate for the degree of anaemia.

In most cases,Chronic kidney disease(CKD) almost always results in anemia because of a deficiency of erythropoietin. Unidentified uremic toxins and retained nitrogen also interfere with the actions of erythropoietin and with red cell production and survival.

Hemolysis and blood loss associated with hemodialysis and bleeding tendencies also contribute to the anemia of renal failure.

Therapy for these anaemias includes treatment for the underlying disease, short-term erythropoietin therapy, iron supplementation, and blood transfusions.

“Anemia of critical illness” is common in the intensive care unit, with more than 90% of patients having subnormal hemoglobin levels by the third day. In critically ill persons, low erythropoietin concentrations and anemia also appear to be caused by inflammatory cytokines.

In this population, it is suggested that red blood cell transfusions be restricted to reduce the risk of transmission of newer infectious agents and immune modulation (e.g., immunosuppression) predisposing to infections, cancer recurrence, and autoimmune disease.



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