title: Predictive features of severe acquired ADAMTS13 deficiency in idiopathic thrombotic microangiopathies: the French TMA reference center experience.
abstract: Severe ADAMTS13 deficiency occurs in 13% to 75% of thrombotic microangiopathies (TMA). In this context, the early identification of a severe, antibody-mediated, ADAMTS13 deficiency may allow to start targeted therapies such as B-lymphocytes-depleting monoclonal antibodies. To date, assays exploring ADAMTS13 activity require skill and are limited to only some specialized reference laboratories, given the very low incidence of the disease. To identify clinical features which may allow to predict rapidly an acquired ADAMTS13 deficiency, we performed a cross-sectional analysis of our national registry from 2000 to 2007. The clinical presentation of 160 patients with TMA and acquired ADAMTS13 deficiency was compared with that of 54 patients with detectable ADAMTS13 activity. ADAMTS13 deficiency was associated with more relapses during treatment and with a good renal prognosis. Patients with acquired ADAMTS13 deficiency had platelet count < 30 x 10(9)/L (adjusted odds ratio [OR] 9.1, 95% confidence interval [CI] 3.4-24.2, P<.001), serum creatinine level < or =200 micromol/L (OR 23.4, 95% CI 8.8-62.5, P<.001), and detectable antinuclear antibodies (OR 2.8, 95% CI 1.0-8.0, P<.05). When at least 1 criteria was met, patients with a severe acquired ADAMTS13 deficiency were identified with positive predictive value of 85%, negative predictive value of 93.3%, sensitivity of 98.8%, and specificity of 48.1%. Our criteria should be useful to identify rapidly newly diagnosed patients with an acquired ADAMTS13 deficiency to better tailor treatment for different pathophysiological groups.
authors.affiliation: Service d'Hématologie et de Thérapie Cellulaire, AP-HP, Hôpital Saint-Antoine, Paris, France. paul.coppo@sat.aphp.fr
authors.forename: Paul
authors.initials: P
authors.lastname: Coppo
authors.forename: Michael
authors.initials: M
authors.lastname: Schwarzinger
authors.forename: Marc
authors.initials: M
authors.lastname: Buffet
authors.forename: Alain
authors.initials: A
authors.lastname: Wynckel
authors.forename: Karine
authors.initials: K
authors.lastname: Clabault
authors.forename: Claire
authors.initials: C
authors.lastname: Presne
authors.forename: Pascale
authors.initials: P
authors.lastname: Poullin
authors.forename: Sandrine
authors.initials: S
authors.lastname: Malot
authors.forename: Philippe
authors.initials: P
authors.lastname: Vanhille
authors.forename: Elie
authors.initials: E
authors.lastname: Azoulay
authors.forename: Lionel
authors.initials: L
authors.lastname: Galicier
authors.forename: Virginie
authors.initials: V
authors.lastname: Lemiale
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Mira
authors.forename: Christophe
authors.initials: C
authors.lastname: Ridel
authors.forename: Eric
authors.initials: E
authors.lastname: Rondeau
authors.forename: Jacques
authors.initials: J
authors.lastname: Pourrat
authors.forename: Stéphane
authors.initials: S
authors.lastname: Girault
authors.forename: Dominique
authors.initials: D
authors.lastname: Bordessoule
authors.forename: Samir
authors.initials: S
authors.lastname: Saheb
authors.forename: Michel
authors.initials: M
authors.lastname: Ramakers
authors.forename: Mohamed
authors.initials: M
authors.lastname: Hamidou
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Vernant
authors.forename: Bertrand
authors.initials: B
authors.lastname: Guidet
authors.forename: Martine
authors.initials: M
authors.lastname: Wolf
authors.forename: Agnès
authors.initials: A
authors.lastname: Veyradier
mesh_terms: D051722:ADAM Proteins / Q000172:deficiency* / Q000276:immunology; D000071120:ADAMTS13 Protein; D000328:Adult; D000368:Aged; D000906:Antibodies; D000974:Antibodies, Antinuclear / Q000097:blood; D003404:Creatinine / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D005602:France; D006801:Humans; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D011237:Predictive Value of Tests; D012042:Registries; D057049:Thrombotic Microangiopathies / Q000150:complications / Q000175:diagnosis* / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000906:Antibodies; D000974:Antibodies, Antinuclear; D003404:Creatinine; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human