Anti-von Willebrand factor aptamer ARC1779 for refractory thrombotic thrombocytopenic purpura

BACKGROUND: Plasma exchange is the main therapy for thrombotic thrombocytopenic purpura (TTP). No treatments other than plasma exchange have been documented to be effective nor are approved for treatment of TTP. The anti-von Willebrand factor (VWF) aptamer ARC1779 effectively inhibits VWF activity in plasma samples of TTP patients and thus shear-dependent platelet (PLT) function as measured by the PLT function analyzer PFA-100 (Dade Behring). It was hypothesized that ARC1779 would offer a potentially effective treatment option for a critically ill patient, refractory to standard care. CASE REPORT: A 39-year-old male patient with idiopathic TTP, refractory to daily plasma exchange, rituximab, steroids, and splenectomy, was additionally treated with a continuous infusion of the anti-von Willebrand factor (VWF) aptamer ARC1779 for 3 weeks. RESULTS: Plasma concentrations of approximately 10 mu g/mL ARC1779 decreased VWF activity by more than 96%. Plasma exchange treatment acutely decreased the plasma concentrations of ARC1779 by a mean of 47% (range, 40%-61%). Thus, additional minibolus infusions of ARC1779 were given after each plasma exchange to rapidly restore steady-state concentrations. ARC1779 resulted in an increase of PLT counts as long as ARC1779 was given. On three occasions the infusion was stopped, each accompanied by a decrease in PLT counts and worsening of microangiopathy. No serious adverse effects were observed during the treatment with ARC1779. CONCLUSION: ARC1779 caused a clear and reproducible increase in PLT counts in an otherwise refractory TTP case. These clinical, pharmacokinetic, and pharmacodynamic data provide a rational basis for clinical trials with ARC1779 in TTP.