Treatment of acquired TTP (aTTP)
A combination of plasma exchange and immunosuppressants is the mainstay of treatment.1 Currently no drugs have been authorized for the treatment of aTTP worldwide.
Plasma exchange, in which a patient’s blood plasma is removed through apheresis and is replaced with donor plasma, removes ULvWF and the circulating autoantibodies against ADAMTS13 and replenishes blood levels of the enzyme. Prior to the introduction of PE treatment, TTP was associated with extremely high mortality (~90%). Although PE has substantially improved survival, in spite of greater understanding of disease pathogenesis and the use of newer immunosuppressants, the mortality rate has not been further impacted.2-7
“…one of the classic features of acquired TTP is the undetectable or deficient ADAMTS13 activity.”
Though considered a relatively safe procedure, in acutely ill patients such as those with aTTP, PE is often associated with major complications8,9 which may be related to the central venous catheter (e.g., infection, thrombosis, catheter insertion complications) or be plasma related (e.g., allergic reactions, alkalosis, volume depletion complications, infection). According to the Oklahoma TTP-HUS Registry, 24% of patients receiving PE followed between 1996-2011 experienced major PE related complications.10
Immunosuppressants are often administered as adjunct to PE in the initial treatment of aTTP.11 Close monitoring of clinical symptoms and regular measurement of platelet counts guide the duration and intensity of PE and immunosuppression. Success of therapy is defined by platelet counts ≥150.000/μL persisting over 48 hours. This is normally accompanied by at least partial recovery of ADAMTS13 activity.
Severe ADAMTS13 deficiency has been recognized as a biomarker in the acute and long-term management of patients with aTTP. During an acute episode, low ADAMTS13 activity levels may guide the intensity or duration of PE and the dose and type of immunosuppressants used.12 Patients experiencing severe ADAMTS13 deficiency during remission are at a 3-fold increased risk of recurrent disease compared to patients without such a deficiency.13 By using ADAMTS13 activity data to tailor therapy for these patients, recurrence may be reduced.14,15
“The primary challenge for accute TTP is to try and increase the platelet count swiftly...”
Treatment of congenital TTP
Current treatment of congenital TTP consists of plasma infusion/exchange or the use of a virally-inactivated intermediate purity factor VIII concentrate containing ADAMTS13.11 Once in remission, subsequent treatment depends on the individual patient.14 Some patients with congenital TTP require plasma infusions every 3–4 weeks in order to replace functional ADAMTS13 and prevent symptomatic TTP episodes, whereas others will only require treatment in the context of inciting factors like pregnancy or infection.14