What are the criteria and causes of anemia?

Anemia Criteria and Causes

Diagnostic Criteria for Anemia

Anemia is defined as hemoglobin below 13.0 g/dL in adult men and below 12.0 g/dL in non-pregnant adult women, with these thresholds aligned to WHO standards and local laboratory reference ranges. 1, 2, 3

Hemoglobin Thresholds by Population:

• Adult men (>15 years): Hb <13.0 g/dL 1, 2
• Non-pregnant women (>15 years): Hb <12.0 g/dL 1, 2
• Pregnant women (2nd/3rd trimester): Hb <11.0 g/dL 1
• Children (6 months-5 years): Hb <11.0 g/dL 2
• Children (5-11 years): Hb <11.5 g/dL 2
• Children (12-13 years): Hb <12.0 g/dL 2

Important Caveats:

• Use your local laboratory's lower limit of normal, but ensure alignment with WHO thresholds 1
• Standard definitions may not apply to elderly individuals (≥70 years), smokers, those at high altitude, non-Caucasian races, or patients with chronic lung disease 2, 3

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Classification and Causes of Anemia

Initial Laboratory Approach

Start with CBC including red cell indices (MCV, MCH), reticulocyte count, and peripheral blood smear to classify anemia mechanistically. 2, 4, 5

The reticulocyte index (RI) distinguishes production versus destruction/loss:

• Low RI (<1.0): Decreased RBC production 1
• High RI (>2.0): Increased production responding to blood loss or hemolysis 1

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Causes by MCV Classification

Microcytic Anemia (MCV <80 fL)

Primary causes: 2, 3

• Iron deficiency anemia (most common)

  • Serum ferritin <30 μg/L is most specific 2, 4
  • Transferrin saturation <15% and elevated TIBC 1, 2
  • MCH may be more sensitive than MCV for detecting iron deficiency 1

• Thalassemia

  • MCV reduced out of proportion to anemia severity 1
  • Requires Hb electrophoresis, especially with appropriate ethnic background 1

• Anemia of chronic disease

  • Normal/elevated ferritin with low iron and transferrin saturation 2
  • Elevated inflammatory markers (CRP, ESR) 2

• Sideroblastic anemia

  • Sideroblasts present on bone marrow biopsy 1

Critical pitfall: Ferritin is an acute phase reactant and may be falsely elevated in inflammatory states despite true iron deficiency—consider transferrin saturation in these cases 1, 2

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Normocytic Anemia (MCV 80-100 fL)

Primary causes: 2, 3

• Acute blood loss

  • Stool guaiac positive, endoscopy findings 1

• Hemolysis

  • Elevated reticulocyte count, decreased haptoglobin, elevated LDH and indirect bilirubin 1, 2
  • Positive direct Coombs test in immune-mediated cases 1, 2

• Anemia of chronic disease/inflammation

  • Normal or low reticulocyte count 2

• Renal insufficiency

  • GFR <60 mL/min/1.73 m², low erythropoietin 1, 4

• Bone marrow failure

  • Pancytopenia, low reticulocyte count 1

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Macrocytic Anemia (MCV >100 fL)

Primary causes: 2, 3

• Vitamin B12 deficiency

  • Low serum B12, elevated methylmalonic acid and homocysteine 2

• Folate deficiency

  • Low serum folate levels 1, 2

• Hypothyroidism 3

• Myelodysplasia 3

• Medications (chemotherapy, antiretrovirals, anticonvulsants) 6

Critical pitfall: Mixed anemias (coexisting iron deficiency and B12/folate deficiency) can present with normal MCV, masking both conditions 2

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Causes by Mechanism

Decreased RBC Production (Low Reticulocyte Count)

• Nutritional deficiencies: Iron, B12, folate 1, 6
• Bone marrow dysfunction: Aplastic anemia, myelodysplasia, malignancy infiltration 1
• Chronic disease/inflammation 2
• Renal disease (decreased erythropoietin) 1, 4
• Endocrine disorders: Hypothyroidism 3
• Medications: Chemotherapy, radiation 1

Increased RBC Destruction or Loss (High Reticulocyte Count)

• Hemorrhage: GI bleeding, menorrhagia 1
• Hemolysis: Immune-mediated, hereditary spherocytosis, G6PD deficiency, DIC 1, 2

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Investigation Thresholds

Any level of anemia with confirmed iron deficiency warrants investigation, though severity increases likelihood of serious GI pathology. 1

NICE Fast-Track Referral Criteria for Suspected GI Cancer:

• Men: Hb <11.0 g/dL with iron deficiency 1
• Non-menstruating women: Hb <10.0 g/dL with iron deficiency 1

Important caveat: These thresholds miss some colorectal cancers, especially in men—maintain lower threshold for investigation 1

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Confirmatory Testing

A hemoglobin rise ≥10 g/L within 2 weeks of iron therapy strongly suggests absolute iron deficiency, even with equivocal iron studies. 1

This therapeutic trial can be diagnostic when laboratory results are unclear, particularly when ferritin is falsely normal due to inflammation 1