Thrombotic Thrombocytopenic Purpura

Reports from University of Paris add new data to research in thrombocytopenic purpura

Thrombotic Thrombocytopenic Purpura Library Library Home This article was published in Hematology Week, which you can subscribe to online.

"ADAMTS13 antigen was qualitatively and quantitatively estimated by electrophoretic analysis and ELISA. Enzymatic activity was qualitatively and quantitatively estimated using GST-VWF73, FRETS-VWF73 fragments and full-length rVWF-WT as substrates. The four mutants and rADAMTS13-WT were present within the cells. Secretion level of rADAMTS13-WT reached 1,200 ng/ml. The four mutations strongly altered the secretion and biological activity of rADAMTS13. The percentage secretion was 21, 38 and 17% for rADAMTS13-S203P, -R268P and -A596V compared with rADAMTS13-WT. rADAMTS13-R507Q concentration was under the detection limit of the assay. In the four cases, no enzymatic activity was detected. After concentration, we confirmed that mutations S203P and R268P totally abolished the proteolytic activity of ADAMTS13. Due to the very low protease concentration, activity of rADAMTS13-R507Q was below the threshold of the assays. rADAMTS13-A596V had no proteolytic activity towards the full-length rVWF-WT whereas it exhibited a decreased specific activity of about 30% of that of rADAMTS13-WT towards FRETS-VWF73 fragment. Binding study of mutated rADAMTS13-S203P, -R268P and -A596V showed that the three mutations strongly decreased the interaction of ADAMTS13 with VWF," wrote A. Hommais and colleagues, University of Paris.

The researchers concluded: "The four mutations, which led to a secretion defect, a loss of enzymatic activity and a decreased binding to the substrate, are responsible for the hereditary TTP in patients."

Hommais and colleagues published their study in Thrombosis and Haemostasis (Molecular characterization of four ADAMTS13 mutations responsible for congenital thrombotic thrombocytopenic purpura (Upshaw-Schulman syndrome). Thrombosis and Haemostasis, 2007;98(3):593-9).

For additional information, contact A. Hommais, INSERM U770 and Universite Paris-Sud, Faculte de Medecine IFR93, Le Kremlin-Bicetre, France.

Publisher contact information for the journal Thrombosis and Haemostasis is: Schattauer GmbH-Verlag Medizin Naturwissenschaften, Holderlinstrasse 3, D-70174 Stuttgart, Germany.

Keywords: France, Le Kremlin-Bicetre, Angiology, Haemostasis, Hematology, Syndrome, Thrombocytopenic Purpura, Thrombosis.

This article was prepared by Hematology Week editors from staff and other reports. Copyright 2007, Hematology Week via NewsRx.com.