• Role of rituximab in increasing early treatment response in participants with TTP who are also treated with plasma exchange and corticosteroids [ Time Frame: Measured at Day 52 ] [ Designated as safety issue: No ]
  

• Use of non-study treatment [ Time Frame: Measured at Month 36 ] [ Designated as safety issue: No ]
  
• Whether participants receiving rituximab achieve early or late treatment response faster and require fewer plasma exchanges than participants not receiving rituximab [ Time Frame: Measured at Days 52 and 82 ] [ Designated as safety issue: No ]
  
• Relationship between clinical and laboratory data and response to treatment [ Time Frame: Measured at Days 52 and 82 ] [ Designated as safety issue: No ]
  
• Incidence of relapse among participants in the two study groups who achieve early treatment response [ Time Frame: Measured at Month 36 ] [ Designated as safety issue: No ]
  
• All cause mortality [ Time Frame: Measured at Month 36 ] [ Designated as safety issue: No ]
  
• Treatment-related complications [ Time Frame: Measured at Day 52 ] [ Designated as safety issue: Yes ]
  
• Evaluating how levels of ADAMTS-13 enzyme and autoantibody at specific time points or over the course of the study correlate with other indicators of disease activity, remission rates, rapidity of achieving a remission, and recurrence rate [ Time Frame: Measured at Month 36 ] [ Designated as safety issue: No ]
  
• Rituximab response in participants with varying levels of ADAMTS-13 activity and antibodies against ADAMTS-13 [ Time Frame: Measured at Month 36 ] [ Designated as safety issue: No ]
  
• Effect of plasma exchange on rituximab levels [ Time Frame: Measured at Month 6 ] [ Designated as safety issue: No ]
  
• Effect of rituximab levels on the extent of B-cell depletion (CD-19+ cells) [ Time Frame: Measured at Month 12 ] [ Designated as safety issue: No ]
  
• B-cell depletion in relation to ADAMTS-13 activity and to ADAMTS-13 antibody levels and disease activity in participants who receive rituximab versus those who do not [ Time Frame: Measured at Month 12 ] [ Designated as safety issue: No ]
  

TTP is a disorder that causes blood clots to form in the small blood vessels throughout the body. If the clots in fact block the blood vessels, blood flow is restricted to various organs, including the brain, kidneys, and heart. This can lead to neurological problems, stroke, abnormal kidney function, and heart problems. Because a large number of platelets are used in the blood clotting process, people with TTP have a reduced number of platelets circulating in their blood. They also have fewer red blood cells circulating in their blood because the red blood cells break down prematurely as blood squeezes past a blood clot.

The primary treatment for TTP is plasmapheresis, also called plasma exchange, which is a procedure that circulates a person's blood through a machine that first removes the damaged plasma and then adds healthy donor plasma into the blood. Next, patients receive a blood transfusion with the new blood. Corticosteroids, a type of medication that reduces the amount of antibodies a person's body makes, are also commonly used in conjunction with plasma exchange to treat TTP. Plasma exchange is usually effective, with platelet and red blood cell counts returning to normal after the procedure is complete. However, some people do experience a relapse of TTP and will require repeat plasma exchanges. Rituximab, an antibody currently used to treat lymphoma and rheumatoid arthritis, may improve immune system response and decrease the number of days needed to undergo the plasma exchange procedure. The purpose of this study is to evaluate the effectiveness of rituximab in combination with plasma exchange at improving an early treatment response in people with TTP and decreasing the likelihood of a relapse of TTP.

This 3-year study will enroll people who have recently been diagnosed with TTP or recently experienced a relapse and have not yet had six plasma exchanges during the current episode of TTP. Participants will be randomly assigned to receive either plasma exchanges and corticosteroids or plasma exchanges, corticosteroids, and rituximab. Blood will be collected from participants at baseline and each day they undergo the plasma exchange procedure. All participants will receive a plasma exchange every day until their platelet counts are normal and signs of tissue damage have improved. Participants will receive corticosteroid medication every day until plasma exchange is stopped, at which time the dosage will be gradually tapered until 7 weeks after the last plasma exchange. Participants receiving rituximab will receive the first dose intravenously within 7 days of the first plasma exchange; they will continue to receive rituximab once a week for 4 weeks. After the plasma exchanges are completed, all participants will have routine follow-up care with their doctors to make sure there is no TTP relapse. In the 1 year after study entry, additional blood collections will occur at varying times. Study researchers will monitor participants' health in the 3 years after study entry by following up with their doctors or through periodic phone calls. A portion of blood will be collected and stored for future TTP research purposes; this is optional.