Introduction:

• It is an anemia that occurs in patients with chronic infections, inflammatory disorders or neoplastic disorders, not due to bleeding, hemolysis or marrow involvement and characterized by hypoferremia but normal iron stores.
• Anemias associated with renal, endocrine or hepatic insufficiency are usually excluded from this category

Etiology:

• Chronic infections
  • Pulmonary infections: abscesses, emphysema, tuberculosis, pneumonia
  • Subacute bacterial endocarditis
  • Pelvic inflammatory disease
  • Osteomyelitis
  • Chronic urinary tract infections
  • Chronic fungal disease
  • Meningitis
  • HIV
• Chronic noninfectious inflammations
  • Rheumatoid arthritis
  • Rheumatic fever
  • Systemic lupus erythematosus
  • Severe trauma
  • Thermal injury
• Malignant diseases
  • Carcinoma
  • Hodgkin’s disease
  • Leukemia
  • Multiple myeloma
• Miscellaneous
  • Alcoholic liver disease
  • Congestive heart failure
  • Thrombophlebitis
  • Obesity
  • Diabetes mellitus
  • Ischemic heart disease

Pathogenesis:

• Cytokines such as IL1, TNF, IL-6 & TGF β, which are produced during inflammation

↓

Reduction in the proliferation of erythroid precursors in response to EPO

Decrease in the EPO production relative to degree of anemia

↓

Apoptosis of bone marrow erythroid cells

• Increased secretion of hepcidin from hepatocytes under influence of IL6

↓

Diminished iron flow to normoblasts

Block in absorption of iron and block in release of iron from macrophages in bone marrow

• Total iron binding capacity is also reduced
• Decreased RBC survival due to

• Nonspecific macrophage activation
• Hemolytic factors elaborated from tumors
• Bacterial toxins

Investigations:

• Peripheral Smear
  • RBCs
    • Early- Normocytic normochromic anemia
    • Then – Normocytic hypochromic anemia
    • Late – Microcytic hypochromic anemia
  • WBC- Normal
  • Platelet – Normal
• Bone marrow examination
  • Essentially normal
  • Increased M: E ratio (Due to decreased erythrocyte precursors)
  • Polychromatophilic normoblasts (Poor hemoglobin production)
  • Sideroblasts - <30%
  • Macrophages contain increased amounts of hemosiderin (Differentiates it from iron deficiency anemia)
  • Increased or normal iron stores
• Reticulocyte production index - <2
• Erythrocyte protoporphyrin level – Increased (As there is a iron deficient erythropoiesis)
• Iron studies
  • Plasma iron level- decreased 
  • TIBC – decreased 
  • Transferrin saturation – >16%
  • Serum ferritin- Normal or increased (Used to differentiate from iron deficiency anemia)
• Soluble transferrin receptor levels: Decreased (Increased in iron deficiency)
• Serum and urine hepcidin – Raised
• C-reactive protein – Usually raised
• ESR – Usually raised

Differential Diagnosis:

• Drug induced bone marrow suppression
• Chronic blood loss
• Renal impairment
• Endocrine disorders
• Metastatic invasion by tumor cells
• Anemia of critical illness: Acute onset anemia, pathogenesis is same as anemia of chronic disease
• Anemia of ageing- Normocytic normochromic anemia with preserved iron stores, Increase ESR

Treatment:

• Treatment of underlying cause
• Treat only if patient is symptomatic or hemoglobin is <10gm/dL
• Transfuse PRBCs with target hemoglobin of 10gm/dL
• High dose Recombinant EPO
  • 150 units/kg- thrice a week
  • Stop if no response at 2 months
  • Target hemoglobin at <12gm/dL (as there is risk or stroke/VTE if hemoglobin is >12gm/dL)
• Drugs under trial
  • Inhibitors of IL6- Elsimomab
  • Inhibitors of hepcidin- 12B9M