Case Presentation: An 82-year-old female presented to the emergency department with a hemoglobin of 5.2 g/dL and complaints of nausea, fatigue, and progressive weakness over the past 2 months. She denied any episode of overt bleeding; no hemoptysis, hematochezia, hematuria, or bloody vaginal discharge. She also denied trauma or any recent falls. The patient’s physical exam findings were unremarkable, and her fecal occult blood test was negative. She was given 2 units of packed red blood cells (RBC) and admitted for further workup. Pertinent lab findings on admission included: BUN of 30 mg/dl, total bilirubin of 2.6mg/dL, RBC count of 1.6 M/mcL, and a lymphocyte percentage of 51.8% on CBC. These findings were suggestive of hemolytic anemia. On day 2 of admission, the patient responded favorably to the blood transfusion with a hemoglobin increase to 8.5g/dl, however, her haptoglobin level remained below 10mg/dL, and RBC count was also below normal levels. The patient’s reticulocyte count was 3.8%, LDH measured 2105 U/L, ferritin measured 795 ng/ml, and her iron levels remained normal. These findings again supported active hemolysis with an anemia of chronic disease. A direct Coombs test was positive for IgG warm agglutinins indicating autoimmune hemolytic anemia. In addition, the consulting gastroenterologist ruled out possible gastrointestinal bleed with a negative esophagogastroduodenoscopy. The patient’s peripheral blood smear and morphology revealed normocytic normochromic anemia, lymphocytosis with atypical and reactive lymphocytes, and smudge cells. Due to the findings of lymphocytosis, flow cytometry was recommended for this patient. On day 6 of admission, her flow cytometry results revealed a CD5 positive B-cell lymphoproliferative disorder with a phenotype characteristic of chronic lymphocytic leukemia (CLL). The diagnosis of autoimmune hemolytic anemia (AIHA) due to CLL was made and the patient was set up to follow hematology & oncology as an outpatient.
Discussion: Chronic Lymphocytic Leukemia is the most common adult leukemia. It is often seen in those over the age of 60 years old. CLL is a neoplastic proliferation of mature B-cells that often co-express CD5 and CD20 markers. The B cells can be characterized by low levels of IgM expression, variable response to antigen stimulation, and activation of signaling pathways that promote tumor survival. In addition, most patients with CLL have germline mutations in the immunoglobin heavy chain region. On peripheral blood smear lymphocytosis and smudge cells can be seen. Complications of CLL include dysregulation of the normal immune system resulting in infections and autoimmune cytopenia with AIHA being the most common. AIHA is an antibody-mediated destruction of autologous red blood cells. Lab findings of AIHA include elevated bilirubin and LDH, low haptoglobin and hemoglobin. AIHA is confirmed with a direct Coombs test positive for warm IgG antibodies on the surface of red blood cells. It is thought that the neoplastic B cells produce improper immunoglobins that then attack the RBCs. Therapy for AIHA include blood transfusion and treatment of CLL with a monoclonal antibody like rituximab.
Conclusions: Chronic Lymphocytic Leukemia can be a slowly progressive cancer that may not be immediately recognized based on patient presentation. Thus, it is important for clinicians to understand various presenting complications such as autoimmune hemolytic anemia. This will ensure patients are quickly diagnosed and receive necessary treatment for CLL.