Here, we report a case of a 17-year old female with Wilson's disease presenting with progressive Coombs' negative hemolytic anemia and hepatic cirrhosis who was treated with one session of therapeutic plasma exchange (TPE) and clinically improved. In clinical situations where multiple sessions of TPE may not be possible, the use of a single session of TPE in conjunction with conventional therapy may be of benefit in preventing further clinical deterioration. J. Clin. Apheresis, 2009. © 2009 Wiley-Liss, Inc.