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• W1976568265 abstract "We read with interest the recent review entitled Management of Thrombotic Thrombocytopenic Purpura (Rock, 2000). The author stated that plasma exchange (PE), alone or combined with drugs, remains the treatment of choice for thrombotic thrombocytopenic purpura (TTP) and it can produce remission in about 80% of patients. There is indeed evidence that patients with TTP have abnormalities in their plasma that may be corrected using PE. Several authors (Furlan et al, 1998; Tsai & Lian, 1998) reported a reduction or absence of a metal-containing proteolytic enzyme (metalloprotease) involved in the cleavage of large von Willebrand factor (VWF) multimers to smaller size molecules. Thus, TTP might result from a deficiency of metalloprotease, which gives rise to an increase of unusually large VWF multimers inducing platelet aggregation. Moreover, immunoglobulin (Ig)G autoantibodies against metalloprotease have been detected in patients with acute TTP. These observations clearly explain the dramatic improvement of the outcome of TTP following the introduction of PE, which removes both large VWF multimers and autoantibodies, and, at the same time, provides new molecules of metalloprotease from normal donors. Nonetheless, approximately 15% of patients fail to respond to PE treatment and may succumb to TTP. Thus, alternative strategies are necessary to successfully treat those cases that do not respond to PE. Unfortunately, no extensive studies have been performed to evaluate the efficacy of other therapeutic strategies. We would like to draw attention to the case of a 20-year-old man whose disease remitted with high-dose cyclophosphamide (Cy) followed by autologous stem cell transplantation (ASCT), as we recently reported (Musso et al, 1999). The patient had been previously treated with PE (28 procedures) and steroids daily (2 mg/kg), and then with weekly pulses of vincristine and intravenous (i.v.) Ig. However, his TTP failed to respond to treatment and we decided to treat the patient with aggressive immunosuppression and ASCT (Fig 1), as high-dose Cy and ASCT have produced profound immunosuppressive and immunomodulatory effects that may have clinical relevance for the treatment of severe autoimmune disorders (Marmont, 1998). Peripheral blood progenitor cells were mobilized with Cy (4 g/m2) plus granulocyte colony-stimulating factor (G-CSF). The conditioning regimen included Cy, anti-T globulin and 6-methylprednisolone. Since receiving ASCT, the patient has maintained complete remission for more than 2 years. In another report, a patient with recurrent TTP was successfully treated with an intensified immunosuppressive regimen consisting of Cy, adriamicin, vincristine and prednisone (Spiekermann et al, 1997). Such therapeutic successes, even if anecdotal, suggest that alternative therapeutic strategies for PE-resistant TTP can be developed and should be further pursued. These alternative treatments were not discussed by Rock (2000) and we would like to draw attention to their potential and the necessity to promote studies that rigorously evaluate alternative treatment strategies for PE-resistant TTP. Temporal changes in PLT count and LDH count." @default.
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• W1976568265 date "2001-05-01" @default.
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• W1976568265 title "Potential strategies for the treatment of plasma exchange-resistant thrombotic thrombocytopenic purpura" @default.
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• W1976568265 doi "https://doi.org/10.1046/j.1365-2141.2001.02782-3.x" @default.
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