A 26-year-old woman comes to the office due to progressive tiredness. The patient has no known chronic medical conditions and takes no medications. Her menstrual periods are regular, and bleeding lasts 3 days. The patient does not use tobacco, alcohol, or illicit drugs. Examination shows no abnormalities. Complete blood count is as follows: Fecal occult blood test is negative. Iron therapy is initiated. When the patient returns 6 weeks later, her laboratory findings are unchanged. Which of the following is the most likely cause of this patient's condition?

Question

A 26-year-old woman comes to the office due to progressive tiredness.  The patient has no known chronic medical conditions and takes no medications.  Her menstrual periods are regular, and bleeding lasts 3 days.  The patient does not use tobacco, alcohol, or illicit drugs.  Examination shows no abnormalities.  Complete blood count is as follows:  Fecal occult blood test is negative.  Iron therapy is initiated.  When the patient returns 6 weeks later, her laboratory findings are unchanged.  Which of the following is the most likely cause of this patient's condition?

Quizplus · Accepted Answer

11ec25c8_d42d_a24d_bc81_3d66bc93a588_MD0003_00 The 2 most common causes of microcytic anemia, iron deficiency and thalassemia minor, have similar laboratory (eg, low mean corpuscular volume [MCV], low mean corpuscular hemoglobin concentration [MCHC]) and peripheral blood smear (eg, target cells, hypochromia) findings. Differentiation requires iron studies, but empiric iron supplementation is sometimes prescribed. Lack of improvement in hemoglobin levels within 4 weeks makes iron deficiency unlikely (Choice I). Therefore, this patient likely has thalassemia, a genetic disorder with hemoglobin defects. Hemoglobin A, the major form of hemoglobin in children and adults, contains 2 alpha-globins and 2 beta-globins. Transcription of the 4 alpha-globin and 2 beta-globin genes is tightly regulated (eg, specific ratio of alpha-/beta-globin production). In thalassemia, mutations or deletions to ≥1 of these genes alter the ratio of alpha-/beta-globin synthesis. Precipitation of excess unpaired globin chains results in erythrocyte toxicity in the bone marrow (ineffective hematopoiesis) and bloodstream (hemolysis). Hemoglobin A Thalassemia severity depends on the number of globin chains affected. Defects in 1 or 2 of the alpha-globin chains (alpha-thalassemia minima or minor) or 1 of the beta-globin chains (beta-thalassemia minor) often cause minimal symptoms. Thalassemia minor is associated with mild/moderate reductions in hematocrit (>28%) and low MCV (55-75 µm³). globin chains affected (Choices A and B) Aplastic anemia (multipotent hematopoietic stem cell injury) and bone marrow infiltration (eg, myelofibrosis, metastatic cancer) are usually associated with pancytopenia and normocytic or macrocytic erythrocytes. (Choices C and K) Circulating antibodies to erythrocyte membranes and traumatic hemolysis (eg, erythrocyte shearing on artificial heart valves) can cause hemolytic anemia, usually associated with normocytic anemia and, sometimes, manifestations of hyperbilirubinemia (eg, icterus). (Choices D and F) Cobalamin (vitamin B₁₂) or folate deficiency leads to macrocytic anemia and hypersegmented neutrophils. (Choice E) Erythropoietin promotes erythrocyte differentiation and maturation. Deficiency, most commonly seen in renal failure, is associated with normocytic anemia. (Choice H) Hereditary spherocytosis is associated with hemolytic anemia due to an erythrocyte membrane defect. MCV is low (small erythrocyte size from the membrane defect), but MCHC is elevated (>36% Hb/cell) due to the increased hemoglobin:cell membrane ratio. (Choice J) Deficiency in erythrocyte glucose-6-phosphate dehydrogenase leads to oxidative injury and subsequent hemolytic anemia. MCV and MCHC are usually normal. Educational objective: The 2 most common causes of microcytic anemia, iron deficiency and thalassemia, are differentiated by iron studies. Thalassemia is a hemoglobin defect caused by alterations to ≥1 of the hemoglobin globin subunits. Thalassemia minor is minimally symptomatic.

A 26-Year-Old Woman Comes to the Office Due to Progressive