The objective of this study was to assess the effect of protein A immunoabsorption in terms of response rate and toxicities in patients with classical thrombotic thrombocytopenic purpura (TTP) refractory to therapeutic plasma exchange. The study included nine females and one male with a diagnosis of classical TTP treated at multiple university hospital centers with protein A immunoabsorption (PAI) after having failed plasma exchange. The 10 patients had an age range 17-62 years. Prior to PAI, the patients had failed to respond to a mean of 15 (range 6-39) therapeutic plasma exchanges. Three patients had previous episodes of TTP. Evaluation for response to PAI included serial measurements of serum creatinine, lactate dehydrogenase (LDH), hemoglobin, hematocrit, and platelet count before, during, and up to 18 months post-PAI treatment. Seven of 10 study patients had resolution of their TTP. Six of the patients required six or fewer therapeutic PAIs and one required 12 treatments. All responding patients had evidence of improvement by the third PAI treatment. Three patients demonstrated no response to PAI, with two patients expiring from complications of TTP and one patient demonstrating a complete response to a subsequent therapy. No significant toxicity was noted with the use of PAI in this setting. Protein A immunoabsorption in patients with classical TTP refractory to plasma exchange can produce durable complete remissions and warrants comparative studies.