Present address: Affiris AG, Vienna, Austria.
Recombinant ADAMTS13 normalizes von Willebrand factor-cleaving activity in plasma of acquired TTP patients by overriding inhibitory antibodies
Article first published online: 6 MAY 2011
© 2011 International Society on Thrombosis and Haemostasis
Journal of Thrombosis and Haemostasis
Volume 9, Issue 5, pages 936–944, May 2011
How to Cite
PLAIMAUER, B., KREMER HOVINGA, J. A., JUNO, C., WOLFSEGGER, M. J., SKALICKY, S., SCHMIDT, M., GRILLBERGER, L., HASSLACHER, M., KNÖBL, P., EHRLICH, H. and SCHEIFLINGER, F. (2011), Recombinant ADAMTS13 normalizes von Willebrand factor-cleaving activity in plasma of acquired TTP patients by overriding inhibitory antibodies. Journal of Thrombosis and Haemostasis, 9: 936–944. doi: 10.1111/j.1538-7836.2011.04224.x
- Issue published online: 6 MAY 2011
- Article first published online: 6 MAY 2011
- Accepted manuscript online: 5 FEB 2011 03:59AM EST
- Received 4 August 2010, accepted 27 January 2011
- anti-ADAMTS13 inhibitors;
- thrombotic thrombocytopenic purpura
Summary. Background: Severe deficiency of the von Willebrand factor (VWF)-cleaving protease ADAMTS13 as observed in acquired thrombotic thrombocytopenic purpura (TTP) is caused by inhibitory and non-inhibitory autoantibodies directed against the protease. Current treatment with plasma exchange is considered to remove circulating antibodies and to concurrently replenish the deficient enzyme. Objectives: To explore the use of recombinant ADAMTS13 (rADAMTS13) as a potential therapeutic agent in acquired TTP, we investigated its efficacy in normalizing VWF-cleaving activity in the presence of ADAMTS13 inhibitors. Methods: Thirty-six plasma samples from TTP patients were adjusted to predefined inhibitor titers, and recovery of ADAMTS13 activity was analyzed following supplementation with rADAMTS13. Results: We showed a linear relation between the inhibitor titer measured and effective rADAMTS13 concentration necessary for reconstitution of VWF-cleaving activity in the presence of neutralizing autoantibodies. Conclusions: Our results support the further investigation of the potential therapeutic applicability of rADAMTS13 as an adjunctive therapy in acquired TTP.