A 22-year-old woman comes to the office due to worsening dyspnea and heart pounding with exercise for the last week. She has no chronic medical conditions but reports aches and pains over the past several weeks. The patient takes ibuprofen as needed but no other medications. Temperature is 37.2 C (99 F), blood pressure is 138/86 mm Hg, and pulse is 90/min. BMI is 18 kg/m2. Physical examination shows an erythematous rash in sun-exposed regions. The lungs are clear to auscultation. A midsystolic click and systolic murmur are heard best at the apex without radiation. There is mild tenderness of joints. Laboratory results are as follows:
| Hemoglobin | 7.8 g/dL |
| Reticulocytes | 6% |
| Platelets | 205,000/mm3 |
| Leukocytes | 11,200/mm3 |
| Creatinine | 1.4 mg/dL |
Which of the following is the most likely cause of this patient's hematologic findings?
Show Explanatory Sources
This patient with dyspnea and heart pounding with exercise has symptomatic anemia. Her other findings, including the presence of joint pain, a photosensitive rash, and mild renal insufficiency, raise suspicion for systemic lupus erythematosus (SLE), an autoimmune disease primarily seen in young women. SLE frequently causes anemia due to a combination of factors, including chronic inflammation (anemia of chronic disease), gastrointestinal serositis (iron deficiency from bleeding), and/or autoimmune hemolytic anemia (AIHA).
Approximately 10% of patients with SLE develop AIHA due to immune dysregulation, which results in the formation of IgG autoantibodies against the erythrocyte membrane. Erythrocytes coated with IgG are subsequently identified by the Fc-receptor on splenic macrophages and partially or wholly phagocytized, leading to extravascular hemolysis. Laboratory assessment typically reveals elevated reticulocyte count (ie, reticulocytosis) because interstitial fibroblasts in the kidney sense tissue hypoxia and increase the release of erythropoietin; this drives the bone marrow to increase erythrocytosis, leading to the presence of immature red cells in the peripheral blood (normoblasts, reticulocytes).
(Choices A and C) The presence of significant reticulocytosis (eg, >4-5%) rules out causes of anemia associated with an impaired bone marrow response, including bone marrow suppression from cancer or infection (eg, parvovirus), anemia of chronic disease (cytokine-mediated retention of iron), and vitamin deficiency (eg, vitamin B12 deficiency from intrinsic factor antibodies, iron deficiency).
(Choice D) A normal platelet count effectively rules out anemia due to a microangiopathic process associated with intravascular platelet consumption (eg, thrombotic microangiopathy).
(Choice E) Although traumatic intravascular hemolysis can occur with a mechanical heart valve or severe aortic stenosis, it is uncommon in otherwise healthy young individuals. Furthermore, this patient's heart murmur is most consistent with mitral valve prolapse, which is common in patients with SLE but rarely causes traumatic hemolysis.
Educational objective:
Anemia with an elevated reticulocyte count (ie, reticulocytosis) indicates that the bone marrow is responding appropriately to the anemia by generating new erythrocytes. Reticulocytosis is commonly seen in patients with hemolysis or acute bleeding. Many other causes of anemia are associated with low reticulocyte count, including bone marrow suppression (eg, parvovirus), iron deficiency anemia, vitamin B12/folate deficiency, and anemia of chronic disease.