Hereditary Form of Thrombotic Thrombocytopenic Purpura
Hrachovinová I., Rittich Š., Salaj P., Suttnar J., Dyr J. E., 1Šuláková T.,1Pták J., 2Ďulíček P., 3Seeman T.
Ústav hematologie a krevní transfuze, Praha 1FNsP, Ostrava 2FN, Hradec Králové 3Pediatrická klinika FNM, Praha
Background. Thrombotic thrombocytopenic purpura is characterized by microvascular platelet clumping resulting in
thrombocytopenia, microangiopathic hemolysis, neurological abnormality, and renal dysfunction. Similar manifestations
also occur in patients with the hemolytic uremic syndrome or other types of disorders. Recent studies demonstrate
that severe deficiency of the von Willebrand factor cleaving metalloprotease, ADAMTS13, causes thrombotic
thrombocytopenic purpura. Aim of our study was to characterize gene defects causing inherited type of disease.
Methods and Results. We investigated nine patients with recurrent type of disease with familiar origin and twelve
relatives. Samples were taken in a remission of disease. We measured activity of ADAMTS13 (vWF-CP) with modified
method of the quantitative immunoblotting of degraded vWF multimers. Mutation screening was carried out by
sequencing all 29 exons and flanking intron regions of the ADAMTS13 gene. Five distinct mutations were found.
Three of them are novel.
Conclusions. Mutation analysis of the ADAMTS13 gene brought interesting results in eight patients. We found a one
single base frameshift insertion, 4143insA in 8 of 9 unrelated individuals. This investigation represents an advantage
in the differential diagnosis of disease since the thrombotic thrombocytopenic purpura phenotype in childhood can be
variable and rapid detection of mutation is helpful for the recurrence prevention
thrombotic thrombocytopenic purpura, ADAMTS13, vWF – cleaving protease, mutations.