Predictive features of severe acquired ADAMTS13 deficiency in idiopathic thrombotic microangiopathies: the French TMA reference center experience.
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.
Coppo
Paul
P
Service d'Hématologie et de Thérapie Cellulaire, AP-HP, Hôpital Saint-Antoine, Paris, France. paul.coppo@sat.aphp.fr
Schwarzinger
Michael
M
Buffet
Marc
M
Wynckel
Alain
A
Clabault
Karine
K
Presne
Claire
C
Poullin
Pascale
P
Malot
Sandrine
S
Vanhille
Philippe
P
Azoulay
Elie
E
Galicier
Lionel
L
Lemiale
Virginie
V
Mira
Jean-Paul
JP
Ridel
Christophe
C
Rondeau
Eric
E
Pourrat
Jacques
J
Girault
Stéphane
S
Bordessoule
Dominique
D
Saheb
Samir
S
Ramakers
Michel
M
Hamidou
Mohamed
M
Vernant
Jean-Paul
JP
Guidet
Bertrand
B
Wolf
Martine
M
Veyradier
Agnès
A
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
D000906:Antibodies; D000974:Antibodies, Antinuclear; D003404:Creatinine; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human