What are the causes of anemia (low red blood cell count)?

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From the Guidelines

Anemia, or a low red blood cell count, is primarily caused by iron deficiency, vitamin B12 or folate deficiency, blood loss, decreased production of red blood cells, or increased destruction of red blood cells. According to the most recent guidelines, the causes of anemia can be evaluated using a morphologic approach, which characterizes anemia based on the mean corpuscular volume (MCV) 1. This approach categorizes anemia into microcytic, normocytic, and macrocytic types, each with distinct underlying causes. For instance, microcytic anemia is most commonly caused by iron deficiency, while normocytic anemia may be caused by hemorrhage, hemolysis, or bone marrow failure 1.

The kinetic approach, on the other hand, focuses on the underlying mechanism of anemia, distinguishing among the production, destruction, and loss of red blood cells 1. A low reticulocyte index (RI) indicates decreased red blood cell production, suggesting iron deficiency, vitamin B12 or folate deficiency, or bone marrow dysfunction 1. In contrast, a high RI suggests normal or increased red blood cell production, indicating blood loss or hemolysis in patients with anemia 1.

More recent guidelines highlight the importance of identifying and treating the underlying cause of anemia, particularly in patients with chronic kidney disease (CKD) 1. In CKD patients, anemia is often multifactorial, involving iron deficiency, haemolysis, and other mechanisms 1. Assessment of iron deficiency in CKD can be challenging, but measurement of ferritin and transferrin saturation can be helpful 1.

Key Causes of Anemia

  • Iron deficiency: most common cause of microcytic anemia 1
  • Vitamin B12 or folate deficiency: causes macrocytic anemia 1
  • Blood loss: can cause normocytic anemia 1
  • Decreased production of red blood cells: can be due to bone marrow failure or dysfunction 1
  • Increased destruction of red blood cells: can be due to hemolysis or other mechanisms 1

Diagnosis and Treatment

  • Evaluate anemia using morphologic and kinetic approaches 1
  • Identify and treat the underlying cause of anemia 1
  • Use iron supplements, vitamin B12 supplements, or folic acid as needed 1
  • Consider blood transfusions for severe anemia 1
  • Manage anemia in CKD patients in conjunction with a nephrologist 1

From the Research

Causes of Anemia

The causes of anemia, a condition characterized by a low red blood cell count, can be diverse and multifaceted. Some of the key causes include:

  • Iron deficiency, which is the most common cause of microcytic anemia 2
  • Blood loss, which can be due to various factors such as gastrointestinal bleeding, surgical intervention, or traumatic injuries 2, 3
  • Nutritional deficiencies, including lack of vitamin B12 and folate 2, 3, 4
  • Renal disease, which can lead to impaired erythropoiesis and anemia 3, 4
  • Malignancy, including solid tumors or hematologic cancer 2
  • Rheumatologic disorders, endocrine disorders, and other systemic diseases 2
  • Reduced red cell life span, which can be caused by inflammatory cytokines or other factors 3
  • Impaired erythropoiesis, which can be due to blunted endogenous erythropoietin production or other factors 3

Specific Causes of Anemia

Some specific causes of anemia include:

  • Hemolytic-uremic syndrome (HUS), which can cause severe anemia due to red blood cell hemolysis and inadequate erythropoietin synthesis 5
  • Chronic diseases, such as kidney disease or cancer, which can lead to anemia due to various factors including blood loss, nutritional deficiencies, and impaired erythropoiesis 6
  • Inherited disorders, such as thalassemia or sickle cell disease, which can cause anemia due to abnormal red blood cell production or function 2

Underlying Factors

Underlying factors that can contribute to the development of anemia include:

  • Age, with older adults being more susceptible to anemia 3
  • Sex, with women being more likely to experience iron deficiency anemia due to menstrual blood loss 2
  • Race, with certain racial or ethnic groups being more prone to specific types of anemia 2

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Hematologic Disorders: Anemia.

FP essentials, 2015

Research

Chronic Anemia and the Role of the Infusion Therapy Nurse.

Journal of infusion nursing : the official publication of the Infusion Nurses Society, 2015

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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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