A 34-year-old woman presents to the clinic with progressive fatigue, lightheadedness, and dark-colored urine over the past two weeks. She has a history of systemic lupus erythematosus (SLE) for which she takes hydroxychloroquine. Vital signs are within normal limits. On physical examination, she appears pale and has mild scleral icterus. There is no lymphadenopathy, but the tip of the spleen is palpable.
Laboratory studies show the following:
Hemoglobin: 7.8 g/dL
Mean corpuscular volume (MCV): 94 fL
Reticulocyte count: 9%
Indirect bilirubin: 2.8 mg/dL
Lactate dehydrogenase (LDH): 450 U/L (Normal: 100–190 U/L)
Peripheral blood smear: Numerous microspherocytes
Which of the following is the most likely result of a direct antiglobulin (Coombs) test in this patient?
The correct answer is:
D) Positive for IgG only
This patient is presenting with warm autoimmune hemolytic anemia (WAIHA), which is frequently associated with underlying autoimmune conditions like SLE or malignancies such as chronic lymphocytic leukemia (CLL). In WAIHA, IgG autoantibodies bind to the surface of red blood cells (RBCs), typically at core body temperature (37°C). As these IgG-coated RBCs pass through the spleen, splenic macrophages recognize the Fc portion of the IgG and nibble away at the red cell membrane. Much like in hereditary spherocytosis, this loss of membrane forces the cell into a spherical shape.
These microspherocytes are eventually destroyed in the spleen (extravascular hemolysis). The direct antiglobulin test (DAT) confirms this by using antibodies against human IgG. A positive result for IgG, and occasionally C3, is the diagnostic hallmark.
Answer choice A: Negative for both IgG and C3, is incorrect. A negative DAT would suggest a non-immune cause of hemolysis, such as microangiopathic hemolytic anemia (thrombotic thrombocytopenic purpura or hemolytic uremic syndrome), G6PD deficiency, or a membrane defect like hereditary spherocytosis.
Answer choice B: Positive for C3 only, is incorrect. A C3 only positive result is more characteristic of cold agglutinin disease (CAD). In CAD, IgM binds to RBCs in cooler peripheral circulation and fixes complement. When the cells return to the warmer core, the IgM dissociates, but the C3 remains on the cell surface.
Answer choice C: Positive for IgA only, is incorrect. While IgA-mediated autoimmune hemolytic anemia exists, it is extremely rare. IgG is the overwhelming cause of warm-type immune hemolysis.
Answer choice D: Positive for IgM only, is incorrect. IgM antibodies usually dissociate from the RBC surface during the washing phase of the Coombs test. Furthermore, IgM-mediated hemolysis is characteristic of cold agglutinin disease, not the warm-reacting IgG process associated with SLE.
Key Learning Point
Warm autoimmune hemolytic anemia is characterized by IgG-mediated extravascular hemolysis. The peripheral smear shows spherocytes, and the diagnosis is confirmed by a Direct Coombs test positive for IgG. It is often secondary to other conditions (SLE, CLL) or medications (e.g., alpha-methyldopa). The first-line treatment is typically corticosteroids.
