Hypochromic Anemia Definition
Hypochromic anemia is defined as anemia characterized by red blood cells with reduced hemoglobin concentration, specifically individual cells containing less than 28 g/dL of hemoglobin, resulting in pale-appearing erythrocytes on peripheral blood smear. 1
Cellular Characteristics
A hypochromic red blood cell is precisely defined as an individual cell with a hemoglobin concentration of less than 28 g/dL. 1
Normally, less than 2.5% of red blood cells are hypochromic in healthy individuals. 1
When hypochromic red blood cells exceed 10%, this indicates functional iron deficiency requiring more intensive iron supplementation, particularly in patients receiving erythropoietin therapy. 1
Morphologic Pattern
Hypochromic anemia typically presents as microcytic hypochromic anemia, where red blood cells are both small (low MCV) and pale (low hemoglobin concentration). 2, 3, 4
The mean corpuscular hemoglobin concentration (MCHC) is reduced, reflecting the decreased hemoglobin content per cell. 1, 5
Red blood cells appear pale with an enlarged area of central pallor on peripheral blood smear examination. 2, 3
Pathophysiology
Hypochromic anemia results when iron deficiency impairs the hemoglobin-building steps of erythropoiesis: both heme and globin synthesis slow, producing reticulocytes that are few, poorly hemoglobinized, and small. 1
The condition reflects inadequate iron availability for hemoglobin synthesis during red blood cell production in the bone marrow. 1, 4
Inflammatory cytokines can stimulate hepatic hepcidin release, which blocks iron absorption and iron release from macrophages, promoting iron-deficiency erythropoiesis and hypochromic red blood cell production. 1
Common Etiologies
Iron deficiency is by far the most common cause of hypochromic anemia, accounting for the vast majority of cases encountered in clinical practice. 2, 3, 4
Other causes include thalassemia syndromes, anemia of chronic disease (which characteristically is hypoproliferative and frequently includes features suggesting iron-deficiency erythropoiesis), and sideroblastic anemia. 1, 3, 4
Lead toxicity can produce hypochromic anemia through impaired heme synthesis. 2
Diagnostic Distinction
In iron deficiency, the percentage of hypochromic cells (mean 34.6%) typically exceeds the percentage of microcytes (mean 12.8%), while in beta-thalassemia trait this pattern is reversed. 6
The microcytic-hypochromic ratio (percentage of microcytes divided by percentage of hypochromic cells) provides discriminant efficiency of 92.4% when using a cutoff value of 0.9, with ratios below 0.9 indicating iron-deficient erythropoiesis. 6
Serum ferritin remains the most definitive non-invasive test for confirming iron deficiency as the cause of hypochromic anemia, though bone marrow assessment of iron stores is the gold standard. 5, 3, 4
Clinical Significance
Hypochromic red blood cells exceeding 6% after intravenous iron supplementation, combined with low to moderate increases in serum ferritin, predict significant benefit from continued iron therapy in hemodialysis patients. 7
The percentage of hypochromic red blood cells serves as the most sensitive parameter for predicting hyporesponsiveness to erythropoietin therapy in patients with elevated C-reactive protein. 7
An increase in hypochromic red blood cells to greater than 10% during erythropoietin therapy indicates functional iron deficiency requiring more intensive iron supplementation. 1