Discussion
Treatment of immune-mediated TTP with PEX aims to eliminate ADAMT13 inhibitors from circulation, and to provide ADAMTS13 in amounts sufficient for cleaving ULVWF, while immunosuppression aims to stop further production of inhibitors by B-lymphocytes and plasma cells. It has been shown that treatment with rituximab in addition to PEX and glucocorticoids increases the probability of achieving remission, reduces the probability of relapse, and shortens the interval to remission.6 Relapses of TTP are common and are due to the continued production of anti-ADAMTS13 antibodies. Hematologic remission are not equivalent to immunologic remission, as levels of ADAMTS13 activity exceeding 5-10% are sufficient in a steady state to maintain the appropriate cleavage of ULVWF.9 Thus, the ultimate goal of TTP treatment is to restore ADAMTS13 activity to normal by eliminating anti-ADAMTS13 antibodies. Historically, many immunosuppressive interventions, such as vincristine, cyclophosphamide, or splenectomy, have been used in patients with TTP with varying degrees of success.
The proteasome inhibitor bortezomib , have proven to be an effective therapy of multiple myeloma, resulting in the long-term suppression of malignant plasma cells. Bortezomib has been used successfully in the treatment of a variety of autoimmune conditions, including TTP, but only one publication has reported its use in adolescents.10-14 In line with published cases, our two patients with short-lived responses to PEX, rituximab, and high-dose glucocorticoids subsequently went into long-term remission with the elimination of inhibitors and normalisation of ADAMTS13 activity after just one course of bortezomib. No side effects of bortezomib were seen, indicating that this treatment is safe and thus suitable for use in children. Monitoring the level of ADAMTS13 activity and inhibitor activity after the achievement of clinical and hematological remission is appropriate for determining the timing of this intervention.
Acknowledgements: Authors wish to thank Vitali Demkin for designing high quality images.
Conflicts of interest : All authors declare no conflict of interest.