title: Congenital and acquired ADAMTS13 deficiency: Two mechanisms, one patient.
abstract: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening microangiopathy with a heterogeneous and largely unpredictable course. It is caused by ADAMTS13 deficiency, that can be either congenital or due to anti-ADAMTS13 autoantibodies development. ADAMTS13 deficiency is necessary but not always sufficient to cause acute clinical manifestations and trigger factors may be needed. We report the case of a woman diagnosed with congenital TTP in her adulthood, presenting with anti-ADAMTS13 autoantibodies in acute phase during ticlopidine consumption. Noteworthy, the two ADAMTS13 mutations identified in this patient are novel: one is a splice-site mutation located in intron 11 (c.1308+2_5delTAGG) and the other is a point missense mutation in exon 29 (c.4184T>C leading to p.Leu1395Pro substitution). Since congenital TTP is an extremely rare disease and drug-induced TTP is an uncommon side effect of treatment with ticlopidine, the simultaneous occurrence of both mechanisms of disease in one patient is exceptional. This case represents TTP as a multifactorial disease, with ADAMTS13 genetic abnormality and environmental exposures acting together in determining individual clinical phenotype.
authors.affiliation: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Angelo Bianchi Bonomi Hemophilia and Thrombosis Centre, Milan, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Ferrari
authors.affiliation: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Angelo Bianchi Bonomi Hemophilia and Thrombosis Centre, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Cairo
authors.affiliation: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Angelo Bianchi Bonomi Hemophilia and Thrombosis Centre, Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Pontiggia
authors.affiliation: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Angelo Bianchi Bonomi Hemophilia and Thrombosis Centre, Milan, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Mancini
authors.affiliation: Oncological Medicine Unit, Azienda Ospedaliera Santa Maria Nuova IRCCS, Reggio Emilia, Italy.
authors.forename: Luciano
authors.initials: L
authors.lastname: Masini
authors.affiliation: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Angelo Bianchi Bonomi Hemophilia and Thrombosis Centre, Milan, Italy.|Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.
authors.forename: Flora
authors.initials: F
authors.lastname: Peyvandi
mesh_terms: D051722:ADAM Proteins / Q000097:blood / Q000172:deficiency* / Q000235:genetics*; D000071120:ADAMTS13 Protein; D000328:Adult; D001323:Autoantibodies / Q000737:chemistry; D004781:Environmental Exposure; D005192:Family Health; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D011697:Purpura, Thrombotic Thrombocytopenic / Q000097:blood / Q000151:congenital / Q000235:genetics*; D013988:Ticlopidine / Q000737:chemistry
chemical_list: D001323:Autoantibodies; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human; D013988:Ticlopidine
keywords: ADAMTS13; congenital; mutation; thrombotic thrombocytopenic purpura; ticlopidine