The purpose is to evaluate safety and feasibility of the use of Rituximab as an adjunct to standard therapy (plasmapheresis + steroids) for patients with thrombotic thrombocytopenic purpura (TTP). This includes evaluating the rate and type of treatment failure.

With this study we hope to evaluate safety and feasibility of the use of Rituximab as an adjunct to standard therapy (plasmapheresis + steroids) for patients with thrombotic thrombocytopenic purpura (TTP). This includes evaluating the rate and type of treatment failure.

Inclusion Criteria:

Patients will be included in the trial based on the following criteria:

• Patients must have TTP with platelet count < 100,000/mL and microangiopathic hemolytic anemia which is defined as presence of at 3-10 fragmented red blood cells (schistocytes) per high power filed on the peripheral blood smear.
• Either gender, age 17 or older
• Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for six months after completion of treatment.
• TTP not related to underlying cancer, treatment of cancer or transplantation
• New onset TTP, or previously diagnosed TTP with an unmaintained remission for >12 months.
• LDH >2X upper limit of normal
• Prothrombin time (PT), partial thromboplastin time (PTT) normal
• Direct antiglobulin test (DAT) negative
• Subject has provided written informed consent
• Patients who have received up to 3 plasmapheresis.

Exclusion Criteria:

Patients will be excluded from the trial based on the following criteria:

• A diagnosis of AIDS. Patients with HIV infection with absolute CD4 counts >200/ul and no active, significant opportunistic infection are eligible
• Patients with a known hepatitis C infection (HCV) and/or with hepatitis B
• Patients receiving pheresis more than once a day
• Recent (within 1 year) bone marrow or hematopoietic stem cell transplant
• Patient is on calcineurin inhibitors, or is unable to come off them
• Acute or chronic disseminated intravascular coagulation (DIC), defined by D-dimers >8mg/ml and fibrinogen < 100 mg (0.1g)/dl
• A diagnosis of metastatic or non-metastatic malignancy other than basal cell carcinoma.
• Malignant hypertension (systolic blood pressure [BP] > 200 mm Hg or a diastolic BP > 130 mm Hg)
• Pregnancy (a negative serum pregnancy test should be performed for all women of childbearing potential within 7 days of treatment). Eligibility resumes 3 days after delivery
• Patients with family history of or a previous diagnosis of congenital TTP
• Patients with hemolytic uremic syndrome (HUS)
• Patients with sepsis