A 68-year-old man comes to the office due to 2 weeks of worsening fatigue and exertional dyspnea. The patient was diagnosed with early-stage chronic lymphocytic leukemia a year ago but has not required treatment because he has not had significant symptoms. Vital signs are within normal limits. Physical examination shows generalized lymphadenopathy and hepatosplenomegaly. Laboratory results are as follows:
| Complete blood count | |
| Hemoglobin | 7.1 g/dL |
| Reticulocytes | 10% |
| Platelets | 210,000/mm3 |
| Leukocytes | 44,800/mm3 (80% lymphocytes) |
Hemoglobin was within normal limits a month ago. Which of the following is the most likely underlying cause of this patient's anemia?
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This patient's fatigue, exertional dyspnea, and low hemoglobin suggest acute symptomatic anemia. Although anemia can be triggered by a wide range of conditions, concurrent clinical data often narrows the differential diagnosis.
In this case, a high reticulocyte count suggests that there are adequate levels of iron, folate, and vitamin B12, to generate new erythrocytes, which makes cytokine-mediated iron dysregulation (eg, anemia of chronic disease) and folate deficiency (eg, leukemic folate consumption) unlikely (Choices A and B). It also suggests that the bone marrow is responding appropriately to the anemia by increasing the production of erythrocytes, which (along with the normal platelet count) makes bone marrow infiltration with leukemic cells less likely (Choice D).
Most cases of anemia with a high reticulocyte count are caused by acute bleeding or hemolysis. In this case, hemolysis is most likely because patients with chronic lymphocytic leukemia often have significant immune dysregulation, which triggers the formation of IgG autoantibodies against the erythrocyte membrane (warm agglutinins). Red blood cells (RBCs) coated with IgG are subsequently identified by the Fc receptor on splenic macrophages and partially or wholly phagocytized, leading to extravascular, immune-mediated hemolysis (ie, autoimmune hemolytic anemia). Patients typically present with signs of acute anemia and RBC lysis (eg, jaundice, dark urine, elevated indirect bilirubin). The diagnosis is confirmed with a direct antiglobulin (Coombs) test, which detects the presence of IgG or C3 (a complement fragment) on erythrocytes.
(Choice E) Autoantibodies against erythroid precursors can lead to pure red cell aplasia, which is marked by anemia with a paucity of reticulocytes (not reticulocytosis).
Educational objective:
Anemia with reticulocytosis suggests that the bone marrow is responding appropriately to the anemia by generating new erythrocytes and that sufficient levels of folate, vitamin B12, and iron are available for erythrocytosis. Anemia with reticulocytosis is commonly seen in acute bleeding conditions and hemolysis. Chronic lymphocytic leukemia is associated with warm autoimmune hemolytic anemia.