How is anemia diagnosed based on different lab values?

Diagnosis of Anemia Based on Laboratory Values

Anemia is diagnosed based on hemoglobin levels below 13.0 g/dL in men and below 12.0 g/dL in women, with further classification and diagnosis determined by red blood cell indices, reticulocyte count, and specific laboratory markers. 1

Definition and Initial Diagnosis

• Anemia is defined by the WHO as hemoglobin below 13.0 g/dL (8.07 mmol/L) in adult men and below 12.0 g/dL (7.45 mmol/L) in non-pregnant adult women 1
• In children, the hemoglobin thresholds vary by age: 11.0 g/dL for ages 6 months to 5 years, 11.5 g/dL for ages 5-11 years, and 12.0 g/dL for ages 12-13 years 1
• Initial laboratory evaluation should include complete blood count (CBC) with red cell indices, reticulocyte count, and peripheral blood smear examination 1

Classification by Red Cell Morphology (MCV)

Microcytic Anemia (MCV < 80 fL)

• Most commonly caused by iron deficiency, thalassemia, anemia of chronic disease, or sideroblastic anemia 1
• Key diagnostic tests include serum ferritin, transferrin saturation (TfS), and CRP 1
• Iron deficiency is confirmed by serum ferritin <30 μg/L in the absence of inflammation 1
• In the presence of inflammation, serum ferritin up to 100 μg/L may still indicate iron deficiency 1
• Red cell distribution width (RDW) helps distinguish iron deficiency (elevated RDW) from thalassemia minor (normal RDW) 1

Normocytic Anemia (MCV 80-100 fL)

• May be caused by acute blood loss, hemolysis, bone marrow failure, anemia of chronic inflammation, or renal insufficiency 1
• Reticulocyte count is crucial for further classification 1
• Low reticulocyte count suggests inadequate bone marrow response or production defect 1
• High reticulocyte count suggests hemolysis or blood loss 1

Macrocytic Anemia (MCV > 100 fL)

• Most commonly megaloblastic, indicating vitamin B12 or folate deficiency 1
• Non-megaloblastic causes include alcoholism, medications (hydroxyurea, diphenytoin), and myelodysplastic syndrome 1
• Requires measurement of vitamin B12 and folate levels 1, 2

Classification by Reticulocyte Count

Low or Normal Reticulocyte Count

• Indicates decreased RBC production 1
• Suggests bone marrow dysfunction, nutritional deficiencies, or anemia of chronic disease 1
• Further workup based on MCV and clinical context 1

High Reticulocyte Count

• Indicates adequate bone marrow response to anemia 1
• Suggests blood loss or hemolysis 1
• Hemolysis workup includes haptoglobin, lactate dehydrogenase, bilirubin, and direct Coombs test 1

Specific Laboratory Tests for Common Anemias

Iron Deficiency Anemia

• Serum ferritin <30 μg/L (most specific marker) 1
• Transferrin saturation <15% 1
• Elevated total iron binding capacity (TIBC) 1
• Increased RDW 1
• Low reticulocyte hemoglobin content 3

Anemia of Chronic Disease

• Normal or elevated serum ferritin 1, 4
• Low serum iron and transferrin saturation 1, 4
• Normal or low TIBC 4
• Normal or slightly elevated RDW 1
• Presence of inflammatory markers (elevated CRP, ESR) 1

Hemolytic Anemia

• Elevated reticulocyte count 1
• Decreased haptoglobin 1
• Elevated lactate dehydrogenase (LDH) 1
• Elevated indirect bilirubin 1
• Positive direct Coombs test in immune-mediated hemolysis 1

Vitamin B12/Folate Deficiency

• Macrocytosis (MCV >100 fL) 1
• Low serum vitamin B12 or folate levels 1, 2
• Hypersegmented neutrophils on peripheral smear 5
• Elevated methylmalonic acid and homocysteine in B12 deficiency 2

Common Pitfalls and Considerations

• Ferritin is an acute phase reactant and may be elevated in inflammatory states despite iron deficiency 1, 4
• Mixed anemias can present with normal MCV when microcytosis and macrocytosis coexist 1
• Standard definitions of anemia may not apply to pregnant women, elderly individuals, smokers, those living at high altitude, or patients with certain chronic conditions 1
• Reticulocyte index must be corrected for the degree of anemia to accurately assess bone marrow response 1
• Multiple causes of anemia may coexist, particularly in elderly patients and those with chronic diseases 2, 4

Algorithm for Anemia Diagnosis

1. Confirm anemia based on hemoglobin levels 1
2. Classify based on MCV (microcytic, normocytic, macrocytic) 1
3. Check reticulocyte count to assess bone marrow response 1
4. For microcytic anemia: check iron studies, consider hemoglobinopathy evaluation 1
5. For normocytic anemia with low reticulocytes: evaluate for chronic disease, renal insufficiency, or early deficiency 1
6. For normocytic anemia with high reticulocytes: evaluate for hemolysis or blood loss 1
7. For macrocytic anemia: check B12 and folate levels, consider medication effects and liver disease 1
8. Consider bone marrow examination when diagnosis remains unclear after initial workup 1, 2