title: Specific von Willebrand factor-cleaving protease in thrombotic microangiopathies: a study of 111 cases.
abstract: Retrospective studies of patients with thrombotic microangiopathies (TMAs) have shown that a deficient activity of von Willebrand factor (vWF)-cleaving protease is involved in thrombotic thrombocytopenic purpura (TTP) but not in the hemolytic-uremic syndrome (HUS). To further analyze the relevance of this enzymatic activity in TMA diagnosis, a 20-month multicenter study of vWF-cleaving protease activity was conducted in adult patients prospectively enrolled in the acute phase of TMA. Patients with sporadic (n = 85), intermittent (n = 21), or familial recurrent (n = 5) forms of TMA (66 manifesting as TTP and 45 as HUS) were included. TMA was either idiopathic (n = 42) or secondary to an identified clinical context (n = 69). vWF-cleaving protease activity was normal in 46 cases (7 TTP and 39 HUS) and decreased in 65 cases (59 TTP and 6 HUS). A protease inhibitor was detected in 31 cases and was observed only in patients manifesting TTP with a total absence of protease activity. Among the 111 patients, mean vWF antigen levels were increased and the multimeric distribution of vWF was very heterogeneous, showing either a defect of the high-molecular-weight forms (n = 40), a normal pattern (n = 21), or the presence of unusually large multimers (n = 50). Statistical analysis showed that vWF-protease deficiency was associated with the severity of thrombocytopenia (P <.01). This study emphasizes that vWF-cleaving protease deficiency specifically concerns a subgroup of TMA corresponding to the TTP entity.
authors.affiliation: INSERM Unité 143, Le Kremlin Bicêtre, France.
authors.forename: A
authors.initials: A
authors.lastname: Veyradier
authors.forename: B
authors.initials: B
authors.lastname: Obert
authors.forename: A
authors.initials: A
authors.lastname: Houllier
authors.forename: D
authors.initials: D
authors.lastname: Meyer
authors.forename: J P
authors.initials: JP
authors.lastname: Girma
mesh_terms: D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; D000328:Adult; D005260:Female; D005500:Follow-Up Studies; D006463:Hemolytic-Uremic Syndrome / Q000097:blood* / Q000175:diagnosis / Q000628:therapy; D006801:Humans; D008297:Male; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011446:Prospective Studies; D011480:Protease Inhibitors / Q000378:metabolism; D011697:Purpura, Thrombotic Thrombocytopenic / Q000097:blood* / Q000175:diagnosis / Q000628:therapy; D012074:Remission Induction
chemical_list: D011480:Protease Inhibitors; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human