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Reports outline thrombocytopenic purpura study findings from University College
April 14th, 2008
2008 APR 14 -- "Thrombotic thrombocytopenic purpura (TTP) is most commonly associated with deficiency or inhibition of von Willebrand factor-cleaving protease (ADAMTS-13) activity. ADAMTS-13 mutations and polymorphisms have been reported in childhood congenital TTP, but their significance in adult onset TTP remains unclear," investigators in London, the United Kingdom report. "We sought to identify common ADAMTS-13 mutations in adults with late onset TTP and to investigate whether they may predispose acute clinical episodes of the disorder in adulthood. Patients/Methods/Results: We detected a missense mutation (C3178T) in exon 24 of ADAMTS-13 in 6/53 (11.3%) adult onset TTP patients, but no normal controls (n = 100). Three of the patients had pregnancy-associated TTP; three had chronic relapsing acute idiopathic TTP. C3178T encodes an arginine to tryptophan (R1060W) substitution in the TSP1-7 domain of ADAMTS-13. In vitro expression of mutant and wild-type ADAMTS-13 demonstrated that R1060W caused severe intracellular retention of ADAMTS-13 (< 5% secretion) without affecting its metalloprotease activity. One homozygous and five heterozygous patients were identified. No other causative mutations were discovered, yet all six patients had ADAMTS-13 activity levels < 5% at presentation (normal: 66-126%). Antibodies/inhibitors to ADAMTS-13 were detected in three/five heterozygous patients, and all six patients had subnormal antigen levels. Six asymptomatic first-degree relatives, including those of two probands with antibodies, were also heterozygous for C3178T; all but one had subnormal ADAMTS-13 activity," wrote R.S. Camilleri and colleagues, University College. The researchers concluded: "The high prevalence of R1060W ADAMTS-13 in adult onset TTP, together with its absence in childhood congenital TTP cases reported elsewhere, suggests it may be a factor in the development of late onset TTP." Camilleri and colleagues published their study in the Journal of Thrombosis and Haemostasis (Prevalence of the ADAMTS-13 missense mutation R1060W in late onset adult thrombotic thrombocytopenic purpura. Journal of Thrombosis and Haemostasis, 2008;6(2):331-338). For additional information, contact R.S. Camilleri, University College London, Dept. of Hematology, Haemostasis Research Unit, 1st Floor, 51 Chenies Mews, London WC1E 6HX, UK. The publisher of the Journal of Thrombosis and Haemostasis can be contacted at: Blackwell Publishing, 9600 Garsington Rd., Oxford OX4 2ZG, Oxon, England. Keywords: United Kingdom, London, Angiology, Enzymology, Haemostasis, Hematology, Protease, Thrombocytopenic Purpura, Thrombosis, Von Willebrand Disease, University College. This article was prepared by Hematology Week editors from staff and other reports. Copyright 2008, Hematology Week via NewsRx.com.
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