Case Presentation: A 32 year old Caucasian female with a fourteen year history of relapsing-remitting MS was admitted to the hospital for evaluation of severe headache, fatigue and dizziness. On physical exam she was tachycardic and very pale. Pertinent labs were as follows: hemoglobin (Hb) 4.1 mg/dL (baseline Hb 10.5 mg/dL), red cell distribution width 17.5 %, reticulocyte count 4.3%, total bilirubin 1.4 mg/dl, (rising to 2.9 mg/dl during the hospital stay), LDH 196 U/L and haptoglobin 98.24 mg/dl. Hemoccult test was negative and no active sources of bleeding were identified. Type and screen was positive for antibodies. Direct Coombs was positive for anti C3 and negative for Anti-IGG. Pending blood matching for observed antibodies, her Hb dropped to 3.5 mg/dL in a couple of hours. On further questioning, she denied any history of blood transfusions, but reported multiple exposures to Alemtuzumab during the past 2 years. The decision was made to transfuse only ABO and Rh matched blood (preceded by 125 mg of methylprednisolone and 25 mg of diphenhydramine), as it was thought that the detected antibodies were likely due to the development of the drug induced AIHA rather than potential reaction to blood products. She received a total of four units of packed red blood cells and was started on high dose intravenous steroids. Her Hb was stable during the hospital stay and she was successfully discharged home on high dose oral steroids.

Discussion: Alemtuzumab is a humanized monoclonal antibody against CD52, used in treatment of relapsing-remitting multiple sclerosis (MS) and B-cell chronic lymphocytic leukemia (CLL). Alemtuzumab causes depletion of CD52 positive B- and T- lymphocytes, followed by reprogramming of immune cell composition. There are reports of effective Alemtuzumab use in treatment of refractory idiopathic and autoimmune hemolytic anemia (AIHA) associated with CLL and adult bowel transplant. We are presenting one of the rare cases of Alemtuzumab as a cause of AIHA . Autoimmune hemolytic anemia associated with the use of Alemtuzumab is a rare but severe side effect, likely requiring close hematological monitoring of patients. Better insight in the mechanism of action, medication interactions as well as patient stratification for use of Alemtuzumab in MS is needed, to avoid potentially fatal side effects.

Conclusions: Opting for emergent blood transfusion in a patient with positive type and screen and positive Coombs test can be challenging, but can save lives. Searching for an etiology as performed in this case should include a meticulous review of medications with their common and rare side effects.