ADAMTS13 and anti-ADAMTS13 antibodies as markers for recurrence of acquired thrombotic thrombocytopenic purpura during remission.
BACKGROUND
From 20 to 50% of patients who survive an acute episode of the acquired form of thrombotic thrombocytopenic purpura relapse but clinical and laboratory markers of recurrence are not well established.


METHODS
In 109 patients enrolled in an international registry we evaluated, in the frame of a retrospective cohort study, the predictive role of the metalloprotease ADAMTS13 as measured in plasma during remission. Anti-ADAMTS13 antibodies and von Willebrand factor were also evaluated in a smaller number of the same patients.


RESULTS
Median values of ADAMTS13 activity and antigen were significantly lower in patients with recurrent thrombotic thrombocytopenic purpura than in those with no recurrence (activity: 12% vs. 41%; p=0.007; antigen: 36% vs. 58%; p=0.003). A severe deficiency of ADAMTS13 activity (10% or less) was associated with a higher likelihood of recurrence (odds ratio 2.9; 95% confidence interval 1.3 to 6.8; p=0.01). Anti-ADAMTS13 antibodies were also more prevalent in patients with recurrent thrombotic thrombocytopenic purpura (odds ratio 3.1; 95% confidence interval 1.4 to 7.3; p=0.006). The presence during remission of both severe ADAMTS13 deficiency and anti-ADAMTS13 antibodies increased the likelihood of recurrence 3.6 times (95% confidence interval 1.4 to 9.0; p=0.006). The presence of ultralarge von Willebrand factor multimers and of associated diseases or conditions did not increase recurrence.


CONCLUSIONS
Survivors of an acute episode of acquired thrombotic thrombocytopenic purpura with severely reduced levels of ADAMTS13 and/or with anti-ADAMTS13 antibodies during remission have an approximately three-fold greater likelihood of developing another episode of thrombotic thrombocytopenic purpura than patients with higher protease activity and no antibody.
Peyvandi
Flora
F
Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, University of Milan, Department of Medicine and Medical Specialities, IRCCS Maggiore Hospital, Mangiagalli and Regina Elena Foundation, Luigi Villa Foundation, Milan, Italy. flora.peyvandi@unimi.it
Lavoretano
Silvia
S
Palla
Roberta
R
Feys
Hendrik B
HB
Vanhoorelbeke
Karen
K
Battaglioli
Tullia
T
Valsecchi
Carla
C
Canciani
Maria Teresa
MT
Fabris
Fabrizio
F
Zver
Samo
S
Réti
Marienn
M
Mikovic
Danijela
D
Karimi
Mehran
M
Giuffrida
Gaetano
G
Laurenti
Luca
L
Mannucci
Pier Mannuccio
PM
D051722:ADAM Proteins / Q000097:blood* / Q000276:immunology; D000071120:ADAMTS13 Protein; D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D011697:Purpura, Thrombotic Thrombocytopenic / Q000097:blood* / Q000276:immunology / Q000401:mortality; D012008:Recurrence; D012042:Registries; D012074:Remission Induction; D012189:Retrospective Studies; D012307:Risk Factors; D014841:von Willebrand Factor / Q000032:analysis / Q000276:immunology
D001323:Autoantibodies; D015415:Biomarkers; D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human