American Society of Hematology

Figure 1.

$Figure 1. The impact of targeted therapy on treatment of TTP. Changes to current management are indicated in red. iTTP remains a clinical diagnosis, and the PLASMIC score can be useful in estimating the probability of ADAMTS13 deficiency. Laboratory testing: ADAMTS13 activity <10% confirms the diagnosis. Monitoring ADAMTS13 can determine safety for stopping caplacizumab and guide preemptive rituximab during remission. Immunosuppression: Early addition of rituximab has previously been studied to prevent exacerbation (though a large RCT has not been completed) and relapse. Early addition of rituximab may be justified to shorten duration of caplacizumab to reduce overall cost and relapse rate. For patients with persistent ADAMTS13 deficiency while on caplacizumab, or those with persistent/recurring thrombocytopenia while on PEX and immunosuppression (refractory ITP), consider agents with reported efficacy in refractory iTTP. These include bortezomib, cyclophosphamide, and vincristine as well as other immunosuppressant agents such as cyclosporine, azathioprine, and mycophenolate. Preemptive rituximab for patients in remission with ADAMTS13 deficiency is an emerging strategy in iTTP. Anti-vWF therapy: Caplacizumab was started on day 1 in the RCTs that showed reduced mortality and refractoriness, and should be used if feasible. Risk of recurrence of TTP is high in patients with persistent ADAMTS13 deficiency; therefore, if caplacizumab is initiated, it should be continued until ADAMTS13 deficiency is resolved. PEX: Many centers taper PEX; this area remains controversial. Although PEX taper is not required (red dashed box) to maintain a normal platelet count, the optimal duration of PEX is not currently known. The high rate of persistent ADAMTS13 deficiency at 30 days after stopping PEX may suggest underuse of PEX (and/or immunosuppression). A tapering schedule of PEX after achieving a normal platelet count has been used to prevent exacerbations, however, this is less likely to be needed if caplacizumab is used although the high cost of caplacizumab may be a barrier to its widespread use. Complications: Caplacizumab is associated with mucocutaneous bleeding. Although rarely serious, the drug has a relatively short half-life and can be withheld until symptoms resolve. vWF concentrates can be used for serious bleeding. iTTP recurrence on anti-vWF therapy is very uncommon and should prompt evaluation for nonadherence and infections, which are known triggers for exacerbation. *The daily dose of caplacizumab was 10 mg in the phase 2 and 3 clinical trials, which was the dose approved by the European Medicines Agency. The US Food and Drug Administration, however, approved a dose of 11 mg daily. IV, intravenously; SC, subcutaneously.$

The impact of targeted therapy on treatment of TTP. Changes to current management are indicated in red. iTTP remains a clinical diagnosis, and the PLASMIC score can be useful in estimating the probability of ADAMTS13 deficiency. Laboratory testing: ADAMTS13 activity <10% confirms the diagnosis. Monitoring ADAMTS13 can determine safety for stopping caplacizumab and guide preemptive rituximab during remission. Immunosuppression: Early addition of rituximab has previously been studied to prevent exacerbation (though a large RCT has not been completed) and relapse. Early addition of rituximab may be justified to shorten duration of caplacizumab to reduce overall cost and relapse rate. For patients with persistent ADAMTS13 deficiency while on caplacizumab, or those with persistent/recurring thrombocytopenia while on PEX and immunosuppression (refractory ITP), consider agents with reported efficacy in refractory iTTP. These include bortezomib, cyclophosphamide, and vincristine as well as other immunosuppressant agents such as cyclosporine, azathioprine, and mycophenolate. Preemptive rituximab for patients in remission with ADAMTS13 deficiency is an emerging strategy in iTTP. Anti-vWF therapy: Caplacizumab was started on day 1 in the RCTs that showed reduced mortality and refractoriness, and should be used if feasible. Risk of recurrence of TTP is high in patients with persistent ADAMTS13 deficiency; therefore, if caplacizumab is initiated, it should be continued until ADAMTS13 deficiency is resolved. PEX: Many centers taper PEX; this area remains controversial. Although PEX taper is not required (red dashed box) to maintain a normal platelet count, the optimal duration of PEX is not currently known. The high rate of persistent ADAMTS13 deficiency at 30 days after stopping PEX may suggest underuse of PEX (and/or immunosuppression). A tapering schedule of PEX after achieving a normal platelet count has been used to prevent exacerbations, however, this is less likely to be needed if caplacizumab is used although the high cost of caplacizumab may be a barrier to its widespread use. Complications: Caplacizumab is associated with mucocutaneous bleeding. Although rarely serious, the drug has a relatively short half-life and can be withheld until symptoms resolve. vWF concentrates can be used for serious bleeding. iTTP recurrence on anti-vWF therapy is very uncommon and should prompt evaluation for nonadherence and infections, which are known triggers for exacerbation. *The daily dose of caplacizumab was 10 mg in the phase 2 and 3 clinical trials, which was the dose approved by the European Medicines Agency. The US Food and Drug Administration, however, approved a dose of 11 mg daily. IV, intravenously; SC, subcutaneously.

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