What are the causes of normocytic anemia?

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From the Guidelines

Normocytic anemia is primarily caused by acute blood loss, hemolysis, chronic disease, bone marrow failure, and renal disease, with the most significant factor being decreased erythropoietin production in renal disease, as evidenced by the most recent study 1. The causes of normocytic anemia can be categorized into several key areas, including:

  • Acute blood loss from trauma, surgery, or gastrointestinal bleeding, which leads to anemia before the body can compensate by changing red cell size
  • Hemolytic anemias resulting from premature destruction of red blood cells due to intrinsic defects like hereditary spherocytosis or extrinsic factors such as autoimmune conditions or mechanical damage
  • Anemia of chronic disease, which occurs with long-term inflammatory conditions, infections, or malignancies where inflammatory cytokines disrupt iron utilization and erythropoiesis, as described in 1
  • Bone marrow failure from aplastic anemia, leukemia, or myelodysplastic syndromes, which reduces red cell production
  • Kidney disease, which causes normocytic anemia through decreased erythropoietin production, as discussed in 1 Other causes of normocytic anemia include:
  • Endocrine disorders such as hypothyroidism or adrenal insufficiency
  • Nutritional deficiencies in early stages
  • Certain medications that suppress bone marrow function It is essential to identify and address the underlying cause of normocytic anemia, as treatment may involve transfusions for severe cases, erythropoiesis-stimulating agents for renal disease, or specific therapies for the primary condition, as recommended in 1 and 1.

From the Research

Causes of Normocytic Anemia

  • Normocytic anemia is characterized by a mean corpuscular volume of 80 to 100 mcm3, and its causes include:
    • Anemia of inflammation 2
    • Hemolytic anemia 2, 3
    • Anemia of chronic kidney disease 2, 4, 5
    • Acute blood loss anemia 2
    • Aplastic anemia 2
  • Anemia of chronic disease is the most common normocytic anemia, found in 6 percent of adult patients hospitalized by family physicians 3
  • Normochromic normocytic anemia regularly develops in chronic renal failure when the glomerular filtration rate drops below 20-30 ml/min, due to reduced red cell life span, blood loss, and inadequate increase in erythropoiesis relative to the fall in hemoglobin 4
  • Anaemia of chronic disease (ACD) is generated by the activation of the immune system, resulting in the release of cytokines that cause an elevation of serum hepcidin, hypoferraemia, suppression of erythropoiesis, decrease in erythropoietin (EPO) and shortening of the half-life of red blood cells 6
  • A deficit in erythropoietin synthesis is the main cause of the normochromic normocytic anemia frequently observed in patients with progressive chronic kidney disease 5

Underlying Conditions

  • Correction of the anemia should focus on managing the underlying condition 2
  • Treatment should be directed at correcting the underlying cause of the anemia 3
  • Controlling the underlying disease and correcting anaemia is the aim of treatment for anaemia of chronic disease 6

Diagnostic Approaches

  • Evaluation begins with a thorough history and a careful physical examination 3
  • Basic diagnostic studies include the red blood cell distribution width, corrected reticulocyte index and peripheral blood smear; further testing is guided by the results of these studies 3
  • Hemolytic anemia can be diagnosed based on signs and symptoms of hemolysis, such as jaundice, hepatosplenomegaly, unconjugated hyperbilirubinemia, increased reticulocyte count, and decreased haptoglobin levels 2

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Anemia: Normocytic Anemia.

FP essentials, 2023

Research

Normocytic anemia.

American family physician, 2000

Research

Pathophysiology of renal anemia.

Clinical nephrology, 2000

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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