Can Macrocytic Anemia with Macrocytes, Target Cells, and Tear-Drop Cells Be Thalassemia?
No, this presentation is highly unlikely to be thalassemia, as thalassemia characteristically causes microcytic anemia (MCV < 80 fL), not macrocytic anemia (MCV > 100 fL). 1
Why This Is Not Thalassemia
Thalassemia Produces Microcytic Anemia
- Thalassemia is consistently classified as a cause of microcytic anemia with MCV < 80 fL 1
- When thalassemia presents with elevated reticulocytes (hemoglobinopathies), it remains microcytic 1
- The fundamental defect in hemoglobin synthesis in thalassemia results in small, hypochromic red blood cells, not large ones 1
Macrocytic Anemia Has Different Causes
The combination of macrocytic anemia (MCV > 100 fL) points toward entirely different etiologies 1:
With low/normal reticulocytes:
- Vitamin B12 or folate deficiency (megaloblastic) 1, 2
- Myelodysplastic syndrome (MDS) 1, 2
- Medications (hydroxyurea, methotrexate, azathioprine, phenytoin) 1
- Hypothyroidism 1
- Alcoholism 1, 2
- Liver disease 2
With elevated reticulocytes:
- Hemolytic anemia (causes "false macrocytosis" from reticulocytosis) 1
The Peripheral Smear Findings Point Elsewhere
Target Cells and Tear-Drop Cells Are Non-Specific
- While target cells can appear in thalassemia, they also occur in liver disease, hemoglobinopathies, and post-splenectomy states 3
- Tear-drop cells (dacrocytes) are particularly concerning for myelofibrosis, MDS, or bone marrow infiltration 1
- The combination of macrocytosis with tear-drop cells strongly suggests a primary bone marrow disorder like MDS rather than thalassemia 1
What You Should Look For Instead
Immediate next steps:
- Examine the peripheral smear for macro-ovalocytes and hypersegmented neutrophils (≥5 lobes), which indicate megaloblastic anemia from B12/folate deficiency 2, 4
- Check reticulocyte count to distinguish between decreased production versus hemolysis 1
- Obtain vitamin B12 and folate levels 1, 2, 4
- Review medication history for drugs causing macrocytosis 1
If megaloblastic features are absent:
- Consider MDS, especially with tear-drop cells present 1
- Evaluate thyroid function and liver enzymes 1, 2
- Assess alcohol use history 1, 2
Critical Caveat: The Rare Exception
There is one extremely rare scenario where thalassemia trait could coexist with macrocytic anemia: when a thalassemic heterozygote develops superimposed folate or B12 deficiency 5. In this unusual situation:
- The underlying microcytosis from thalassemia may be "masked" by the macrocytic process 5
- The MCV might normalize or even become elevated 5
- However, this would still not be "thalassemia causing macrocytic anemia"—it would be two separate conditions occurring simultaneously 5
Bottom line: If you see true macrocytic anemia with MCV > 100 fL, pursue the standard macrocytic anemia workup, not thalassemia evaluation. 1, 2, 4