Case Presentation: A 76-year-old female with a past medical history of hypertension, hyperlipidemia, and hypothyroidism presented to the hospital with fatigue and headaches that had been ongoing for a few days. The patient had chronic watery diarrhea but denied having any dark stool, hemoptysis, or recent antibiotic use. On physical exam, vitals were stable, she had skin pallor and no blood on rectal exam. Lab-work revealed WBC: 29.9 10*3/uL, Hgb: 7.3 g/dL, Hct: 21.3%, MCV: 117.7 fL, Plt: 42 10*3/uL, LDH: 525 U/L, haptoglobin: 2 mg/dL, reticulocyte count: 24.20%, direct bilirubin: 0.6 mg/dL, and total bilirubin: 2.2 mg/dL. ANA and Anti-SSA were positive, however the rest of the autoimmune workup was negative. Mycoplasma pneumonia IgM antibody, EBV IgM antibody, babesia PCR, and myositis panel returned negative. CT angiogram of the abdomen and pelvis with and without intravenous contrast revealed no evidence of acute GI bleed. CT chest without intravenous contrast revealed multiple bilateral pulmonary nodules and masses that may represent metastasis along with mediastinal right hilar adenopathy. Peripheral blood smear revealed no schistocytes. The patient was found to be Coombs positive for both warm and cold antibodies/agglutinin, which led to the diagnosis of mixed autoimmune hemolytic anemia (AIHA). The patient required transfusions with fresh frozen plasma, warm packed red blood cells, and platelets during the course. Bone marrow biopsy was negative for lymphoproliferative disorder and a right lung biopsy was negative for malignancy. For the patient’s AIHA, the patient was started on intravenous methylprednisolone, which was later transitioned to an oral prednisone taper. Following bone marrow biopsy, the patient was started on rituximab weekly for four weeks. Outpatient PET scan revealed patchy atelectatic and ground-glass opacities in both lungs which correlate to inflammatory etiology and multiple small lung nodules with minimal or no FDG activity. MRI of the brain with contrast revealed no malignancy.
Discussion: AIHA is an acquired hemolytic disease caused by the host’s immune system acting against its own red cell antigens. Various subtypes of AIHA exist, including warm AIHA, cold AIHA, and mixed AIHA. The incidence of AIHA is 1-3 per 100,000 per year, however mixed AIHA only account for 10% of those cases. Mixed AIHA can be caused by lymphoma, lupus, infection, or be idiopathic. Our patient did not have a malignancy or infection. ANA was positive, however dsDNA antibodies for lupus were negative. Lab values that may suggest a diagnosis of AIHA include anemia that may be normocytic or macrocytic, elevated LDH, reduced haptoglobin, increased reticulocyte count, and elevated unconjugated bilirubin. Peripheral blood smear may reveal polychromasia or spherocytes. A direct-antiglobulin test or Coombs test detects antibodies and/or complement on the red blood cells to confirm the diagnosis. Due to its rarity, optimal management has not been defined. The use of steroids for management has provided mixed results based on case reports written in literature. Rituximab, a monoclonal CD20 antibody, has been found to be an effective therapy for mixed AIHA.
Conclusions: Mixed AIHA is a rare hemolytic anemia that physicians should keep in their differentials to allow for prompt diagnosis and treatment. Further treatment investigations should be conducted to find the optimal treatment for the disease.