A 24-year-old woman of Southeast Asian descent presents for a routine physical examination. She is asymptomatic and denies fatigue, shortness of breath, or heavy menstrual cycles. She has no significant past medical history and takes no medications. A complete blood count is ordered and shows a hemoglobin of 11.2 g/dL, a mean corpuscular volume (MCV) of 71 fL, and an red blood cell (RBC) count of 5.9 million/μL. A serum ferritin and iron panel are within normal limits. Hemoglobin electrophoresis shows normal levels of HbA, HbA2, and HbF.
Which of the following is the most likely diagnosis?
The correct answer is:
A) Alpha thalassemia trait
This patient presents with microcytic anemia, but her RBC count is disproportionately high (erythrocytosis). In the setting of microcytosis with a normal iron panel, which rules out iron deficiency) a hemoglobinopathy should be suspected. The Mentzer Index (MCV / RBC count) is a helpful clinical tool to distinguish between iron deficiency and thalassemia trait. An index of less than 13 strongly suggests thalassemia:
Mentzer Index=5.9×1012/L71 fL≈12.03
Because the patient is of Southeast Asian descent, alpha thalassemia is statistically much more likely than beta thalassemia. Alpha thalassemia occurs due to the deletion of one or more of the four α-globin genes. In the trait form where there are two gene deletions, the patient is typically asymptomatic with mild microcytic anemia. Crucially, hemoglobin electrophoresis in adults with alpha thalassemia trait is often normal, because there is still sufficient alpha-globin production to form HbA, HbA2, and HbF.
Answer choice B: Anemia of chronic disease, is incorrect. Anemia of chronic disease usually presents with normocytic or mild microcytic anemia, but it typically lacks the erythrocytosis seen here. Additionally, it is characterized by abnormal iron studies, specifically an increased ferritin level, reflecting iron sequestration in macrophages, which contradicts the normal findings in this patient.
Answer choice C: Beta thalassemia trait, is incorrect. Beta thalassemia trait would present with similar red blood cell indices (microcytic, elevated RBC count). However, the diagnosis is usually confirmed by hemoglobin electrophoresis, which typically reveals an elevated HbA2 (often >3.5%). Since this patient's electrophoresis is entirely normal, beta thalassemia trait is less likely.
Answer choice D: Iron deficiency anemia, is incorrect. While iron deficiency is the most common cause of microcytic anemia, it is unlikely here. Iron deficiency typically presents with a low RBC count and elevated Mentzer index (>13). Furthermore, this patient has normal iron studies (ferritin and iron panel), which excludes iron deficiency.
Answer choice E: Sideroblastic anemia, is incorrect. Sideroblastic anemia is characterized by a defect in heme synthesis, leading to iron accumulation in mitochondria. It typically presents with a dimorphic peripheral smear with both microcytic and normocytic cells and often shows abnormal iron studies with high serum iron and ferritin levels. It does not present as a classic asymptomatic microcytosis in a young adult.
Key Learning Point
When faced with microcytic anemia and normal iron studies, check the RBC count. A high RBC count with low MCV is highly suggestive of thalassemia. Alpha thalassemia trait is a clinical diagnosis of exclusion, often supported by a normal hemoglobin electrophoresis in an asymptomatic patient from an at-risk ethnic population.
