Case Presentation: A 20-year-old female with history of primary membranous nephropathy, hypertension, iron deficiency anemia, preeclampsia, and intrauterine fetal demise presented to the hospital with weakness, 2-3 days of upper respiratory symptoms, dyspnea, nausea, vomiting, and diarrhea. Labs showed normocytic anemia with hemoglobin of 3.3 g/dL worsening to 1.9 g/dL pending blood transfusion and leukocytosis of 27.9 x10^3 cells/uL. She denied symptoms of bleeding and the only medication she took was losartan. Workup revealed elevated reticulocyte count (12.4%), LDH of 835 U/L, and haptoglobin < 10 mg/dL. Peripheral blood smear showed spherocytes with evidence of red cell regeneration. Direct antiglobulin test was positive for IgG. Further workup showed negative ANA, EBV, RPR, Hepatitis A/B/C, COVID, CMV, HIV, parvovirus B19, and antiphospholipid antibodies. Flow cytometry showed 0.2% myeloid blasts, likely reactive. Respiratory panel returned with positive adenovirus, suspected to be an inciting factor. She required four units of packed red blood cells for severe anemia. She received IV methylprednisolone, later transitioned to 50 mg of oral prednisone under guidance of hematology oncology who are tentatively planning for outpatient rituximab. After 3 days in the hospital, hemoglobin improved to 7.2 g/dL, with her baseline hemoglobin level being 8-10 g/dL.
Discussion: Here we present a case of warm autoimmune hemolytic anemia (w-AIHA) due to viral infection. This is a rare disease with incidence of 1:100,000 occurring as result of increased RBC destruction from antibodies binding to red blood cell antigens (1). It is suspected that molecular mimicry between pathogen and self-antigens is a possible mechanism of pathogenesis (2). w-AIHA can present without inciting factors (primary) (3). Alternatively, w-AIHA can be associated with malignancy such as CLL, autoimmune conditions such as lupus, medications such as penicillin, and infectious syndromes (secondary) (4). Common viral infections associated with w-AIHA include HIV, EBV, hepatitis C, and CMV (5). Adenovirus associated w-AIHA is rare. In fact, one study from France found only one patient out of 219 pediatric cases of w-AIHA had concomitant adenovirus (6). Glucocorticoids are the first line treatment for w-AIHA and are effective in 80-90% of cases (7). Sometimes rituximab may be added as part of first line treatment (5). Of note, the average hemoglobin seen in patients with w-AIHA is about 7 d/dL (8). Only a few cases exist of hemodynamically stable patients with hemoglobin count between 1 and 2 g/dL (9,10). In these cases, the patients have iron-deficiency anemia, which this patient also has and is most likely contributing to her extreme anemia
Conclusions: Although rare, w-AIHA with concomitant adenovirus infection should be suspected in patients who have unexplained anemia in setting of recent adenovirus infection. Prompt recognition of w-AIHA can prevent morbidity and mortality given high likelihood of response with steroids and improvement of anemia as seen in this case.