A 45-year-old woman has experienced worsening arthritis of her hands and feet for the past 15 years. On physical examination, there are marked deformities of the hands and feet, with ulnar deviation of the hands and swan-neck deformities of the fingers. Laboratory studies show an elevated level of rheumatoid factor. CBC shows hemoglobin, 11.6 g/dL; hematocrit, 34.8%; MCV, 87 mm3; platelet count, 268,000/ mm3; and WBC count, 6800/ mm3. There is a normal serum haptoglobin level, serum iron concentration of 20 mg/ dL, total iron-binding capacity of 195 mg/dL, percent saturation of 10.2, and serum ferritin concentration of 317 ng/mL. No fibrin split products are detected. The reticulocyte concentration is 1.1%. What is the most likely mechanism underlying this patient's hematologic abnormalities?
The iron concentration and iron-binding capacity are low; however, in contrast to the finding in anemia of iron deficiency, the serum ferritin level is increased. This increase is typical of anemia of chronic disease. In this case, the chronic disease is rheumatoid arthritis. Underlying chronic inflammatory or neoplastic diseases increases the secretion of cytokines such as interleukin-1, tumor necrosis factor, and interferon-g. These cytokines promote the sequestration of iron in storage compartments and depress erythropoietin production. Autoantibody hemolytic anemias occur in several autoimmune diseases, such as systemic lupus erythematosus, but not usually in patients with rheumatoid arthritis, as in this case. Normal serum haptoglobin rules out intravascular hemolysis; iron is recycled at a rapid rate. Impaired synthesis of b-globin chains gives rise to b-thalassemia, also characterized by hemolysis. Complement lysis is enhanced in paroxysmal nocturnal hemoglobinuria, which results from mutations in the PIGA gene. Patients with this disorder have a history of infections. Sequestration of RBCs in the spleen occur when RBC membranes are abnormal, as in hereditary spherocytosis or sickle cell anemia, or RBCs are coated by antibodies, as in autoimmune hemolytic anemias. Metastases are space-occupying lesions (myelophthisic process) that can lead to leukoerythroblastosis, with nucleated RBCs and immature WBCs appearing on the peripheral blood smear.
Autoantibodies against RBC membranes
Impaired synthesis of b-globin chains
Inadequate usage of stored iron
Sequestration of RBCs in splenic sinusoids
Blood