Thrombotic thrombocytopenic purpura Diagnosis and management Initial evaluation Diagnose TTP on the basis of clinical history, examination and routine laboratory parameters, including blood film review. A Obtain serological tests for human immunodeficiency virus, HBV and HCV, autoantibody screen, and a pregnancy test when appropriate, at presentation. A ADAMTS13 activity and anti-ADAMTS13 antibodies Obtain pre-treatment samples to measure ADAMTS13 activity levels and detect anti- ADAMTS13 antibodies. Recognize that measurement of ADAMTS 13 antigen levels is also useful in congenital TTP. B General principles Q Does the patient have microangiopathic hemolytic anemia and thrombocytopenia in the absence of an other identifiable cause? No Consider alternative diagnoses. Yes Treat TTP as a medical emergency. A Plasmapheresis Initiate plasma exchange immediately, preferably within 4-8 hurs, in patients with microangiopathic hemolytic anemia and thrombocytopenia in the absence of any other identifiable clinical cause. B Perform plasma exchange with 1.5 times plasma volume exchanges, using solvent detergent treated plasma in all age groups, and reassess therapy daily. B Consider reducing the volume of exchange to 1.0 times plasma volume when the clinical condition and laboratory test results are stabilizing. C Consider increasing the frequency and/or volume of plasma exchange procedures in patients with life-threatening TTP. C Continue daily plasma exchange for a minimum of 2 days after platelet count has been > 150, 000/ L. B Blood product transfusion Do not administer platelet transfusions in patients with TTP unless there is life- threatening hemorrhage. D Administer packed RBC transfusion according to clinical need especially if there is cardiac involvement. A Corticosteroids Consider initiating IV methylprednisolone (1,000 mg IV daily for 3 consecutive days in adults) or high-dose oral prednisolone (1 mg/kg PO daily). B Folate supplementation Initiate folate supplements in patients with active hemolysis. A Rituximab BCSH Q Does the patient have acute idiopathic TTP with neurologic/cardiac pathology? Yes Consider initiaitng rituximab, in conjunction with plasma exchange and corticosteroids, in patients with acute idiopathic TTP with neurological or cardiac involvement. B No Patients with HIV Q Does the patient have human immunodeficiency virus infection? Yes Measure viral load and closely involve an human immunodeficiency virus physician in the management of patients with TTP and human immunodeficiency virus infection. A Initiate plasma exchange in conjunction with antiretroviral therapy as soon as the diagnosis of human immunodeficiency virus-associated TTP is made. B Administer antiretroviral therapy immediately after plasma exchange therapy to maximize time for absorption. A Continue antiretroviral therapy after remission to prevent further relapse. B Consider initiating rituximab in patients with resistant human immunodeficiency virus- related TTP. C No Management of refractory disease BCSH Q Does the patient have refractory TTP? Yes Initiate rituximab in patients with refractory immune-mediated TTP. B Consider adding rituximab and increasing the frequency of plasma exchange in patients with refractory TTP. B No Management of relapse BCSH Q Does the patient have relapsing TTP? Yes Perform plasma exchange at an increased dose and/or add rituximab therapy in patients with relapsing disease. B Consider initiating cyclosporin A as second-line therapy in patients with acute or chronic relapsing acquired TTP. B No Thromboprophylaxis Q Has the patient's platelet count reached > 50 10 /L? Yes Administer thromboprophylaxis with LMWH in patients reached platelet count > 50, 000/ L. B Antiplatelet agents Consider initiating low-dose aspirin (75-81 mg PO daily) during platelet recovery (platelet count has reached > 50, 000/ L). C No General counseling Counsel patients and provide with verbal and written information about symptoms, signs and risk of relapse before discharge. A Counsel patients to avoid medications associated with precipitation of TTP to prevent disease relapse, including quinine and estrogen-containing medications. B Offer non-estrogen containing contraception in female patients with previous TTP. B