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March 20, 2018; 90 (12) Article

Usefulness of ADAMTS13 to predict response to recanalization therapies in acute ischemic stroke

Alejandro Bustamante, MingMing Ning, Teresa García-Berrocoso, Anna Penalba, Cristina Boada, Alba Simats, Jorge Pagola, Marc Ribó, Carlos Molina, Eng Lo, Joan Montaner
First published February 14, 2018, DOI: https://doi.org/10.1212/WNL.0000000000005162
Alejandro Bustamante
From the Neurovascular Research Laboratory (A.B., T.G.-B., A.P., C.B., A.S., J.M.), Institut de Recerca, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain; Clinical Proteomics Research Center and Cardio-Neurology Clinic (M.N., E.L.), Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA; and Stroke Unit (J.P., M.R., C.M.), Hospital Universitari Vall d'Hebron, Barcelona, Spain.
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MingMing Ning
From the Neurovascular Research Laboratory (A.B., T.G.-B., A.P., C.B., A.S., J.M.), Institut de Recerca, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain; Clinical Proteomics Research Center and Cardio-Neurology Clinic (M.N., E.L.), Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA; and Stroke Unit (J.P., M.R., C.M.), Hospital Universitari Vall d'Hebron, Barcelona, Spain.
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Teresa García-Berrocoso
From the Neurovascular Research Laboratory (A.B., T.G.-B., A.P., C.B., A.S., J.M.), Institut de Recerca, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain; Clinical Proteomics Research Center and Cardio-Neurology Clinic (M.N., E.L.), Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA; and Stroke Unit (J.P., M.R., C.M.), Hospital Universitari Vall d'Hebron, Barcelona, Spain.
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Anna Penalba
From the Neurovascular Research Laboratory (A.B., T.G.-B., A.P., C.B., A.S., J.M.), Institut de Recerca, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain; Clinical Proteomics Research Center and Cardio-Neurology Clinic (M.N., E.L.), Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA; and Stroke Unit (J.P., M.R., C.M.), Hospital Universitari Vall d'Hebron, Barcelona, Spain.
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Cristina Boada
From the Neurovascular Research Laboratory (A.B., T.G.-B., A.P., C.B., A.S., J.M.), Institut de Recerca, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain; Clinical Proteomics Research Center and Cardio-Neurology Clinic (M.N., E.L.), Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA; and Stroke Unit (J.P., M.R., C.M.), Hospital Universitari Vall d'Hebron, Barcelona, Spain.
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Alba Simats
From the Neurovascular Research Laboratory (A.B., T.G.-B., A.P., C.B., A.S., J.M.), Institut de Recerca, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain; Clinical Proteomics Research Center and Cardio-Neurology Clinic (M.N., E.L.), Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA; and Stroke Unit (J.P., M.R., C.M.), Hospital Universitari Vall d'Hebron, Barcelona, Spain.
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Jorge Pagola
From the Neurovascular Research Laboratory (A.B., T.G.-B., A.P., C.B., A.S., J.M.), Institut de Recerca, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain; Clinical Proteomics Research Center and Cardio-Neurology Clinic (M.N., E.L.), Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA; and Stroke Unit (J.P., M.R., C.M.), Hospital Universitari Vall d'Hebron, Barcelona, Spain.
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Marc Ribó
From the Neurovascular Research Laboratory (A.B., T.G.-B., A.P., C.B., A.S., J.M.), Institut de Recerca, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain; Clinical Proteomics Research Center and Cardio-Neurology Clinic (M.N., E.L.), Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA; and Stroke Unit (J.P., M.R., C.M.), Hospital Universitari Vall d'Hebron, Barcelona, Spain.
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Carlos Molina
From the Neurovascular Research Laboratory (A.B., T.G.-B., A.P., C.B., A.S., J.M.), Institut de Recerca, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain; Clinical Proteomics Research Center and Cardio-Neurology Clinic (M.N., E.L.), Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA; and Stroke Unit (J.P., M.R., C.M.), Hospital Universitari Vall d'Hebron, Barcelona, Spain.
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Eng Lo
From the Neurovascular Research Laboratory (A.B., T.G.-B., A.P., C.B., A.S., J.M.), Institut de Recerca, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain; Clinical Proteomics Research Center and Cardio-Neurology Clinic (M.N., E.L.), Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA; and Stroke Unit (J.P., M.R., C.M.), Hospital Universitari Vall d'Hebron, Barcelona, Spain.
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Joan Montaner
From the Neurovascular Research Laboratory (A.B., T.G.-B., A.P., C.B., A.S., J.M.), Institut de Recerca, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain; Clinical Proteomics Research Center and Cardio-Neurology Clinic (M.N., E.L.), Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA; and Stroke Unit (J.P., M.R., C.M.), Hospital Universitari Vall d'Hebron, Barcelona, Spain.
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Citation
Usefulness of ADAMTS13 to predict response to recanalization therapies in acute ischemic stroke
Alejandro Bustamante, MingMing Ning, Teresa García-Berrocoso, Anna Penalba, Cristina Boada, Alba Simats, Jorge Pagola, Marc Ribó, Carlos Molina, Eng Lo, Joan Montaner
Neurology Mar 2018, 90 (12) e995-e1004; DOI: 10.1212/WNL.0000000000005162

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Abstract

Objective We aimed to analyze ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) in relation to arterial recanalization in patients treated with IV tissue plasminogen activator (tPA) and in relation to futile recanalization in patients treated with mechanical thrombectomy.

Methods Acute ischemic stroke patients (n = 108) with documented arterial occlusions treated with IV-tPA were selected. ADAMTS13 activity was measured by ELISA in samples collected before treatment. Recanalization was assessed at 2 hours by transcranial Doppler. In 78 consecutive patients treated with endovascular thrombectomy, ADAMTS13 antigen was measured by ELISA and futile recanalization was defined as complete recanalization plus modified Rankin Scale score >2 at 3 months. Independent predictors of recanalization and futile recanalization were determined by logistic regression, adjusted by age, NIH Stroke Scale score, and time from stroke onset.

Results Patients who achieved tPA-induced recanalization had higher baseline ADAMTS13 activity (78.1% [68%–88%] vs 70.1% [61%–79%], p = 0.021). In logistic regression analysis, ADAMTS13 activity >75% was an independent predictor of recanalization (odds ratio = 6.76 [1.52–30.02], p = 0.012), together with absence of early ischemic signs and Oxfordshire Community Stroke Project classification. Regarding endovascular therapies, a reduced ADAMTS13 concentration (<982 ng/mL) was an independent predictor of futile recanalization (odds ratio = 67.4 [1.4–3,282.1], p = 0.034), together with age and diabetes mellitus. The addition of ADAMTS13 to clinical predictors of tPA-induced recanalization and futile recanalization improved discrimination and reclassification (integrated discrimination improvement = 10.06% and 28.4%, net reclassification improvement = 61.0% and 107.4%, respectively).

Conclusions A reduced ADAMTS13 was associated with poor response to recanalization therapies. If confirmed in future prospective studies, a panel of blood biomarkers including ADAMTS13 might be a useful tool to guide reperfusion therapies.

Glossary

ADAMTS13=
a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13;
ASPECTS=
Alberta Stroke Program Early CT Score;
IDI=
integrated discrimination improvement;
NIHSS=
NIH Stroke Scale;
NRI=
net reclassification improvement;
OCSP=
Oxfordshire Community Stroke Project;
OR=
odds ratio;
POCI=
posterior circulation infarct;
TACI=
total anterior circulation infarct;
TICI=
thrombolysis in cerebral ischemia;
tPA=
tissue plasminogen activator;
vWF=
von Willebrand factor

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Personalizing acute therapies for ischemic stroke: Thrombolysis or thrombectomy? 535

  • Received March 22, 2017.
  • Accepted in final form December 12, 2017.
  • © 2018 American Academy of Neurology
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Letters: Rapid online correspondence

  • Author response to Gavriilaki et al.
    • Alejandro Bustamante, Neurologist, Neurovascular Research Laboratory, Vall d'Hebron Institute of Research, Universitat Autonoma de Barcelona
    • Joan Montaner, Neurologist, Neurovascular Research Laboratory, Vall d'Hebron Institute of Research, Universitat Autonoma de Barcelona
    Submitted May 08, 2018
  • ADAMTS13 in acute ischemic stroke: Antigen, activity, or nothing?
    • Maria Gavriilaki, Physician, Postgraduate Course, Medical Research Methodology, Aristotle University of Thessaloniki (Thessaloniki, Greece)
    • Ioanna Sakellari, Director Hematologist, Hematology Department-BMT Unit, G. Papanicolaou Hospital (Thessaloniki, Greece)
    • Vasileios Kimiskidis, Professor of Neurology, 3rd Department of Neurology, Aristotle University of Thessaloniki (Thessaloniki, Greece)
    Submitted March 27, 2018
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