Clinical Significance of Elliptocytes in a 35-Year-Old Patient
Elliptocytes on a CBC in a 35-year-old patient most commonly indicate hereditary elliptocytosis (HE), which is typically asymptomatic and requires no treatment, though you must evaluate for hemolytic anemia and exclude other causes of elliptocytosis.
Initial Assessment Approach
The presence of elliptocytes requires systematic evaluation to determine clinical significance:
Quantify the Elliptocytes
- Assess the percentage of elliptocytes on peripheral smear - HE typically shows >25% elliptocytes, though the diagnosis can be made with lower percentages if accompanied by family history 1
- Look for accompanying morphologic features including rod-shaped cells, fragmented red blood cells, and microspherocytes, which may indicate more severe variants 2
Evaluate for Hemolysis
- Check hemoglobin level - Most HE patients are asymptomatic with normal or near-normal hemoglobin, but some experience hemolytic anemia 1
- Assess reticulocyte count - An elevated reticulocyte count suggests active hemolysis 3
- Look for indirect hyperbilirubinemia and jaundice - These may be present intermittently in symptomatic patients 1, 4
- Examine for splenomegaly - This can occur in patients with hemolytic anemia 1, 5
Complete Blood Count Analysis
- Review MCV (mean corpuscular volume) - HE is typically normocytic, but marked microcytosis with two RBC populations suggests hereditary pyropoikilocytosis (HPP), a severe variant 2
- Assess all cell lines - Abnormalities in multiple cell lines warrant hematology referral 3
Differential Diagnosis Considerations
Hereditary Elliptocytosis (Most Likely)
- HE is especially common in individuals of African and Mediterranean ancestry due to presumed malaria resistance 1
- The majority of HE patients are completely asymptomatic and require no intervention 1
- Genetic basis involves mutations in spectrin or protein 4.1R genes (alpha-spectrin, beta-spectrin, or EPB41), causing mechanical weakness of the RBC membrane skeleton 1, 4
Other Causes to Exclude
- Iron deficiency - Check ferritin and transferrin saturation, as iron deficiency can produce elliptocytes and is more clinically significant 3
- Myelodysplastic syndromes - Consider if other cytopenias are present 6
- Thalassemia - Can coexist with HE and produce moderate anemia with marked poikilocytosis 7
When to Refer to Hematology
Refer to hematology if:
- Symptomatic anemia is present (fatigue, pallor, tachycardia) 4
- Evidence of significant hemolysis (elevated reticulocyte count, jaundice, splenomegaly) 1, 5
- Multiple cell line abnormalities are detected on CBC 3
- Marked microcytosis with fragmented cells suggesting HPP 2
- Transfusion requirement develops 4
Management for Asymptomatic Cases
For asymptomatic patients with isolated elliptocytosis:
- No treatment is required - The vast majority of HE patients remain asymptomatic throughout life 1
- Family screening may be considered - HE is inherited in an autosomal dominant pattern, and family members may have similar findings 4, 5
- Genetic counseling can be offered if the patient desires information about inheritance patterns 4
Critical Pitfall to Avoid
Do not assume elliptocytes are always benign - While most HE cases are asymptomatic, approximately 10-15% of patients develop clinically significant hemolytic anemia requiring intervention, and delayed diagnosis can occur even into the fourth decade of life 4, 2. The case report of a 34-year-old woman with previously undiagnosed hereditary pyropoikilocytosis demonstrates that moderate manifestations can present late 2.