A 55-year-old man comes to the office due to several months of progressive fatigue. He does not have chest pain or shortness of breath. Medical history is significant for hypertension and obesity. BMI is 45 kg/m². Examination shows mild mucosal pallor. Laboratory results are as follows: Which of the following is the most likely cause of this patient's anemia?

Question

Quizplus · Accepted Answer

11ec160b_3aed_1544_9249_95359e366af1_MD0001_00 This patient with morbid obesity has normocytic anemia with a low reticulocyte count, raising strong suspicion for anemia of chronic disease (ACD). Because ACD is triggered by long-standing elevations in serum inflammatory cytokines, it is classically associated with underlying rheumatologic disease, persistent infection, or malignancy. However, ACD is also commonly caused by less obvious sources of inflammation such as type 2 diabetes mellitus, congestive heart failure, severe traumatic injury, and morbid obesity. The major inflammatory cytokine that drives ACD is hepcidin, a small peptide released from the liver in response to inflammation or bacterial lipopolysaccharide. Hepcidin binds to and inhibits iron channels (ferroportin) on the surface of enterocytes and reticuloendothelial macrophages, leading to decreased iron absorption in the gut and decreased iron release by the reticuloendothelial system (which supplies ~95% of daily iron for erythropoiesis). Because heme synthesis is impaired without sufficient iron, patients with ACD typically develop a normocytic (or slightly microcytic) anemia with a minimal reticulocyte response. (Choice B) Extravascular hemolysis typically occurs due to the formation of IgG autoantibodies against the erythrocyte membrane, which results in erythrocyte destruction by splenic macrophages. Patients generally develop an acute normocytic anemia with a strong (not suppressed) reticulocyte response. (Choice C) Microangiopathic hemolytic anemia is associated with shearing of red blood cells in the microvasculature due to the formation of fibrin-rich platelet clots. Patients typically have normocytic anemia, significant reticulocytosis, and severe thrombocytopenia (~10,000/mm³). (Choice D) Iron deficiency anemia (IDA) from an occult gastrointestinal bleed is common in older individuals. IDA is also associated with a low reticulocyte count. Although IDA can cause mild normocytic anemia early in the disease course, by the time individuals develop profound anemia (eg, hemoglobin of 8.6 mg/dL), they almost always have severe microcytosis (eg, MCV < 70). This patient's severe anemia is accompanied by a normal MCV, making iron deficiency anemia highly unlikely. (Choice E) Vitamin B₁₂ deficiency is associated with macrocytic (not normocytic) anemia due to impaired maturation of erythrocytes. Educational objective: Anemia of chronic disease (ACD) occurs in patients with rheumatologic diseases, chronic infection, malignancy, congestive heart failure, and morbid obesity due to chronic elevation of inflammatory cytokines. The primary mediator is hepcidin, a peptide released from the liver that inhibits iron channels on enterocytes and reticuloendothelial macrophages. This reduces iron availability for erythropoiesis, which leads to normocytic (or slightly microcytic) anemia with a poor reticulocyte response.

A 55-Year-Old Man Comes to the Office Due to Several