title: The course of ADAMTS-13 activity and inhibitor titre in the treatment of thrombotic thrombocytopenic purpura with plasma exchange and vincristine.
abstract: The therapeutic efficacy of plasma exchange (PE) in thrombotic thrombocytopenic purpura (TTP) is attributed to the restoration in ADAMTS-13 (a disintegrin and metalloproteinase with thrombospondin motif-13) activity by substitution of the enzyme and removal of ADAMTS-13-neutralizing autoantibodies. We explored this rationale by analysing ADAMTS-13 activity and corresponding inhibitor levels during PE-treatment in 27 episodes from 23 adults with TTP. All patients with an initial episode of TTP (n = 14) and nine of 11 patients with a relapse showed severe ADAMTS-13 deficiency. ADAMTS-13 inhibitors were detected in 81% of these patients. Twenty-one patients responded to PE-therapy and two patients died. For patients with severe ADAMTS-13 deficiency, 15 patients (71%) showed a PE-induced recovery in ADAMTS-13 activity and six patients (29%) had persistent severe ADAMTS-13 deficiency despite clinical response. Three patients with recurrent TTP demonstrated a permanent increase in inhibitor titre during therapy. Six patients (43%) with an initial episode of TTP displayed a transient increase in inhibitor titre during PE-therapy, which was associated with deterioration in clinical and haematological symptoms of TTP. Treatment with vincristine induced an immediate increase in platelet count and ADAMTS-13 activity in seven of eight patients. We conclude that ADAMTS-13 activity and inhibitor levels, as measured using current methodology, do not solely determine the clinical course of TTP.
authors.affiliation: Department of Internal Medicine, Johann Wolfgang Goethe University Hospital, Frankfurt am Main, Germany. m.boehm@em.uni-frankfurt.de
authors.forename: Martina
authors.initials: M
authors.lastname: Böhm
authors.forename: Christoph
authors.initials: C
authors.lastname: Betz
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Miesbach
authors.forename: Manuela
authors.initials: M
authors.lastname: Krause
authors.forename: Charis
authors.initials: C
authors.lastname: von Auer
authors.forename: Helmut
authors.initials: H
authors.lastname: Geiger
authors.forename: Inge
authors.initials: I
authors.lastname: Scharrer
mesh_terms: D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000097:blood*; D008875:Middle Aged; D010951:Plasma Exchange; D010976:Platelet Count; D011480:Protease Inhibitors / Q000378:metabolism; D011697:Purpura, Thrombotic Thrombocytopenic / Q000201:enzymology* / Q000276:immunology / Q000628:therapy*; D012008:Recurrence; D000069283:Rituximab; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D014750:Vincristine / Q000627:therapeutic use*; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D011480:Protease Inhibitors; D014841:von Willebrand Factor; D000069283:Rituximab; D014750:Vincristine; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human