Microcytic Anemia with Elevated Red Blood Cell Count in an Elderly Asian Woman
This 79-year-old Asian woman has alpha thalassemia trait (most likely alpha-thalassemia minor), not iron deficiency anemia, based on the markedly elevated RBC count (6.5 ×10⁶/µL), severe microcytosis (MCV 73.4 fL), and disproportionately mild reduction in hemoglobin relative to the degree of microcytosis.
Diagnostic Reasoning
Key Laboratory Pattern
The elevated RBC count (6.5 ×10⁶/µL) combined with severe microcytosis (MCV 73.4 fL) is the pathognomonic feature of thalassemia trait, distinguishing it from iron deficiency anemia, which typically shows a normal or reduced RBC count. 1
Alpha thalassemia is the most common cause of microcytic anemia in Southeast Asian populations, accounting for 28-55% of cases in this demographic, making it the primary diagnostic consideration in this patient. 2
The hematocrit of 47.7% is actually elevated (normal range for elderly women is approximately 36-44%), indicating relative erythrocytosis rather than anemia, which further supports thalassemia trait over iron deficiency. 1
Parents of patients with alpha thalassemia can be screened by evaluation of mean cell volume, which will be <80 fL in thalassemia carriers, and this patient's MCV of 73.4 fL falls well below this threshold. 2
Distinguishing from Iron Deficiency
Iron deficiency anemia typically presents with low or normal RBC counts because the bone marrow cannot produce adequate numbers of red cells without sufficient iron, whereas thalassemia trait shows compensatory erythrocytosis with uniformly small cells. 1, 3
The RDW/RBC ratio is a highly reliable discriminant index with 100% specificity for distinguishing beta-thalassemia trait from iron deficiency in Asian populations; calculating this ratio (RDW divided by RBC count) would provide additional diagnostic clarity. 3
In the four patients with secondary polycythemia and incidental iron deficiency who were given iron, the RBC count remained above normal and the MCV rose to normal, demonstrating that elevated RBC count with microcytosis persists in thalassemia even after iron repletion. 1
Essential Confirmatory Testing
First-Line Diagnostic Studies
Order serum ferritin and transferrin saturation immediately to exclude coexisting iron deficiency, as ferritin <30 µg/L would confirm depleted iron stores, while ferritin >100 µg/L makes absolute iron deficiency unlikely. 4, 5
Hemoglobin electrophoresis should be performed to confirm alpha thalassemia trait by demonstrating the characteristic hemoglobin pattern, particularly when microcytosis is present with normal or borderline iron studies. 4, 5
Measure C-reactive protein concurrently with ferritin because ferritin is an acute-phase reactant that can be falsely elevated by inflammation, potentially masking coexisting iron deficiency in elderly patients. 4, 5
Interpretation Algorithm
If ferritin is <30 µg/L and transferrin saturation <16%: Combined alpha thalassemia trait with iron deficiency is present; treat with oral iron supplementation (ferrous sulfate 325 mg once to three times daily) and monitor hemoglobin response. 4, 5
If ferritin is 30-100 µg/L: Measure transferrin saturation; if <16-20%, iron deficiency is confirmed despite borderline ferritin, especially in the presence of inflammation. 4, 5
If ferritin is >100 µg/L and transferrin saturation >20%: Isolated alpha thalassemia trait is the diagnosis; no iron supplementation is indicated, and genetic counseling should be offered if family planning is relevant. 4, 5
Critical Clinical Pitfalls
Common Diagnostic Errors
Do not assume all microcytic anemia in Asian populations is iron deficiency; the elevated RBC count in this case is a red flag that should immediately prompt consideration of thalassemia trait before initiating empiric iron therapy. 5
Do not rely on MCV alone to distinguish thalassemia from iron deficiency, as both conditions produce severe microcytosis; the RBC count is the critical discriminating parameter, with thalassemia showing elevated counts and iron deficiency showing normal or reduced counts. 1, 3
Patients with thalassemia trait should not receive iron supplementation unless concurrent iron deficiency is documented by low ferritin and transferrin saturation, as unnecessary iron therapy can lead to iron overload. 4
Do not overlook combined deficiencies; iron deficiency can coexist with thalassemia trait, recognizable by an elevated RDW, and both conditions must be addressed. 4
Age-Specific Considerations
In elderly patients, ferritin may be falsely elevated by chronic inflammation, malignancy, or hepatic disease, so transferrin saturation <16-20% should be used as the primary indicator of iron deficiency when ferritin is in the 30-100 µg/L range. 4, 5
The hematocrit of 47.7% in a 79-year-old woman warrants evaluation for secondary causes of erythrocytosis (hypoxia, renal disease, smoking) if thalassemia trait is confirmed, although the elevated RBC count with microcytosis strongly favors thalassemia as the primary etiology. 1
Management Approach
If Isolated Thalassemia Trait is Confirmed
No treatment is required for isolated alpha thalassemia trait, as it is a benign condition that does not cause anemia or require intervention. 4
Genetic counseling should be offered if the patient has children of childbearing age, as homozygous alpha-thalassemia (Bart's hydrops fetalis) is lethal and occurs when both parents carry the trait. 2
Document the diagnosis prominently in the medical record to prevent future unnecessary iron supplementation or invasive investigations for microcytosis. 5
If Coexisting Iron Deficiency is Identified
Initiate oral iron supplementation with ferrous sulfate 325 mg once to three times daily; a rise in hemoglobin of ≥10 g/L within 2 weeks confirms iron-deficiency anemia even when initial iron studies are equivocal. 4, 5
Investigate the source of iron loss in elderly patients, with gastrointestinal blood loss being the most common etiology; upper endoscopy with duodenal biopsies and colonoscopy are warranted to exclude malignancy, angiodysplasia, or celiac disease. 2, 5
Monitor hemoglobin and iron indices at 3-month intervals for one year after correction of anemia to ensure iron stores are replenished and to detect recurrent deficiency. 5