The course of ADAMTS-13 activity and inhibitor titre in the treatment of thrombotic thrombocytopenic purpura with plasma exchange and vincristine.
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.
Böhm
Martina
M
Department of Internal Medicine, Johann Wolfgang Goethe University Hospital, Frankfurt am Main, Germany. m.boehm@em.uni-frankfurt.de
Betz
Christoph
C
Miesbach
Wolfgang
W
Krause
Manuela
M
von Auer
Charis
C
Geiger
Helmut
H
Scharrer
Inge
I
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
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