Will a patient with hemolytic anemia have a normal serum iron level?

From the Guidelines

A patient with hemolytic anemia is likely to have a normal or elevated serum iron level, rather than a low level, due to the premature destruction of red blood cells and the subsequent release of iron back into circulation. This is because, in hemolytic anemia, the iron from destroyed red blood cells is recycled by the body and becomes available for new red blood cell production, thus maintaining normal or even increased serum iron levels despite the anemia 1.

Key Points to Consider

• Hemolytic anemia is characterized by the premature destruction of red blood cells, which leads to the release of iron into the circulation.
• The recycling of iron from destroyed red blood cells maintains normal or elevated serum iron levels.
• Laboratory findings in hemolytic anemia include elevated indirect bilirubin, increased lactate dehydrogenase (LDH), decreased haptoglobin, and reticulocytosis.
• The British Society of Gastroenterology guidelines for the management of iron deficiency anemia in adults recommend confirming iron deficiency through iron studies, including serum ferritin and transferrin saturation 1.

Clinical Implications

• Understanding the difference in serum iron levels between hemolytic anemia and iron deficiency anemia is crucial for proper diagnosis and management.
• A good response to iron therapy, as defined by a hemoglobin rise of ≥10 g/L within a 2-week timeframe, is highly suggestive of absolute iron deficiency, even if iron study results are equivocal 1.
• However, in the context of hemolytic anemia, the focus should be on managing the underlying cause of the hemolysis rather than solely on iron supplementation.

From the Research

Hemolytic Anemia and Serum Iron Levels

• Hemolytic anemia is characterized by the premature destruction of red blood cells, which can lead to various laboratory findings, including changes in serum iron levels 2.
• A study from 1975 found no correlation between iron concentration and degree of hemolysis in patients with hemolytic anemia, with only a few patients showing a marked increase in serum iron 2.
• The diagnosis of hemolysis is based on the presence of anemia with sustained reticulocytosis, and additional findings may include increased unconjugated bilirubin, LDH, and free hemoglobin, as well as decreased haptoglobin and hemopexin 3, 4.
• The morphology of the red cell is abnormal in almost all cases of hemolytic anemia, and the direct antiglobulin test can help differentiate immune causes from nonimmune causes 4.
• Hemolytic diseases are classified into hemoglobinopathies, membranopathies, enzymopathies, immune-mediated anemias, and extrinsic nonimmune causes, and medications can cause hemolytic anemia through several mechanisms 4.
• A study from 2025 found that mouse models of genetic anemia, including sickle cell disease, beta-thalassemia, and hereditary spherocytosis, exhibit distinct patterns of hemolysis, erythropoiesis, and iron distribution 5.
• While these studies provide insight into the pathophysiology of hemolytic anemia, they do not directly address the question of whether a patient with hemolytic anemia will have a normal serum iron level.
• However, based on the available evidence, it appears that serum iron levels may not be directly correlated with the degree of hemolysis, and patients with hemolytic anemia may have varying serum iron levels depending on the underlying cause and severity of the disease 2, 5.