Can anemia occur with normal hemoglobin (Hb) levels?

From the Guidelines

Anemia can indeed occur even with normal hemoglobin levels in certain situations, and clinicians should consider a comprehensive approach to identify such cases. This condition is known as "masked anemia" or "relative anemia." It typically happens when there's a change in plasma volume that affects the concentration of hemoglobin in the blood. For example, during pregnancy, a woman's blood volume increases significantly, which can dilute the hemoglobin concentration 1. While her absolute hemoglobin amount may be low (indicating anemia), the measured concentration might appear normal due to this dilution effect. Similarly, in conditions like dehydration, hemoglobin concentration may appear normal or even elevated despite an actual deficiency in red blood cells. Other situations where anemia might be masked include acute blood loss with inadequate fluid replacement, or in patients with polycythemia who develop iron deficiency.

Some key points to consider when evaluating for anemia include:

• Hematocrit and red blood cell count
• Indices like MCV (mean corpuscular volume)
• The patient's clinical context, such as the presence of chronic disease, thalassemia, or vitamin B12/folate deficiency 1
• Serum markers of iron deficiency, including low ferritin, low transferrin saturation, and raised total iron-binding capacity 1
• The distinction between iron deficiency anemia and anemia of chronic disease, which is important in conditions like inflammatory bowel disease 1

By considering these factors, clinicians can identify cases of anemia that may not be immediately apparent from hemoglobin levels alone, and provide appropriate treatment to improve patient outcomes. For instance, iron supplementation may be necessary in cases of iron deficiency anemia, while treatment of the underlying condition may be more effective in cases of anemia of chronic disease 1.

From the Research

Anemia with Normal Hemoglobin Levels

• Anemia is a complex condition that can occur even with normal hemoglobin (Hb) levels, as the definition of anemia varies by age, sex, and ethnicity 2, 3.
• Normal Hb distribution ranges are:
  • <12.0 g/dL in women and <13.0 g/dL in men, according to the World Health Organization (WHO) 3.
  • New lower limits of normal Hb values have been proposed, taking into account ethnicity, gender, and age 3.
• Anemia can be classified into different types, including:
  • Iron deficiency anemia (microcytic anemia) 2, 4.
  • Normocytic anemia, which has a broad differential diagnosis, including nutritional deficiencies, blood loss, renal disease, and systemic diseases 2, 4.
  • Macrocytic anemia, associated with vitamin B12 and folate deficiency, among other conditions 2, 5.

Diagnosis and Evaluation

• The diagnosis of anemia involves a detailed history, physical examination, and laboratory tests, including:
  • Mean corpuscular volume (MCV) to guide the differential diagnosis and evaluation 2, 4.
  • Reticulocyte count and red blood cell distribution width index to assess bone marrow function and erythropoiesis 2, 5.
  • Serum ferritin level to diagnose iron deficiency anemia 4.
• In some cases, anemia may be "unexplained" and not attributed to a specific underlying disease or pathological process 3.

Treatment and Management

• Treatment of anemia is directed at the underlying cause and may involve:
  • Iron replacement therapy for iron deficiency anemia 2, 4.
  • Vitamin B12 and folate supplementation for deficiency-related anemias 2, 6.
  • Blood transfusions for severe anemia or symptomatic patients 4.
• Normalization of hemoglobin levels typically occurs within 8 weeks of treatment in most patients 4.