BACKGROUND: Congenital thrombotic thrombocytopenic purpura (TTP) is defined by persistent severe deficiency of ADAMTS-13 in the absence of anti-ADAMTS-13 inhibitory antibodies, confirmed by mutational analysis. Replacement of the missing protease prevents disease relapse, primarily using plasma infusion (PI). OBJECTIVES, PATIENTS AND METHODS: There is scant evidence regarding optimal dose and frequency of treatment, tending to be empirically guided. We present a pharmacokinetic analysis of ADAMTS-13 in 6 patients with congenital TTP on established regimes following PI. RESULTS: We found a median clearance of 25.41ml/h and half-life of 130 hours, ranging between 82.6 and 189.5 hours (3.4 to 7.9 days respectively). All patients reached baseline ADAMTS-13 level within 7-10 days post plasma. Median ADAMTS-13 activity peak post PI was 24.05IU/dL. Variation was related to elimination rate, in turn affected by weight and metabolism, but not to von Willebrand factor antigen or activity levels. Using the pharmacokinetic parameters, we simulated individualised protocols based on PI dose or frequency to target hypothetical optimal plasma levels of ADAMTS-13 of 10 and 50IU/dL respectively. Results suggest a target trough ADAMTS-13 of 10IU/dL is feasible but 50IU/dL would not be achievable taking into account volume required. CONCLUSIONS: Further work is needed to compare treatment of congenital TTP with PI versus recombinant ADAMTS-13. PI may provide longer duration of ADAMTS-13 effect, but is limited by plasma volume required, whereas recombinant therapy can provide a higher ADAMTS-13 peak. We propose that investigation of interindividual clearance of ADAMTS-13 is necessary to optimise treatment, to enable rationale for dose and frequency of prophylaxis
