ADAMTS-13 activity in the presence of elevated von Willebrand factor levels as a novel mechanism of residual platelet reactivity in high risk coronary patients on antiplatelet treatment

Rossella Marcucci, Francesca Cesari, Sandro Cinotti, Rita Paniccia, Gian Franco Gensini, Rosanna Abbate, Anna Maria Gori

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background: The pathophysiologic mechanisms leading to residual platelet reactivity (RPR) on antiplatelet therapy, a condition high prevalent in patients with acute coronary syndrome, are not yet elucidated. In the acute phase of coronary artery disease large amounts of ultra large VWF multimers (ULVWF) are released and cleaved by the activity of ADAMTS-13. Objective: Aim of this study was to evaluate the relationships between VWF antigen (VWF:Ag) levels, collagen binding activity of VWF (VWF:CB), ADAMTS-13 and interleukin-6 (IL-6) levels in affecting platelet response to dual antiplatelet treatment. Methods: In 159 acute coronary syndrome (ACS) patients undergoing percutaneous coronary interventions we measured platelet function by platelet aggregation with two agonists [1 mM arachidonic acid (AA) and 10 μM ADP]. We defined patients with RPR those with platelet aggregation by AA > 20% and/or ADP (10 μmol) > 70%. Results: We found significantly lower ADAMTS-13 activity, elevated IL-6, VWF:Ag and VWF:CB levels in patients with RPR. A lower ADAMTS-13 activity was present in patients with VWF:Ag and VWF:CB in the upper tertile. At the multivariate analysis ADAMTS-13 activity and IL-6 were independent risk factors for RPR. Conclusion: Our results indicate that ADAMTS-13 activity and IL-6 levels independently affect RPR and suggest that, by different pathways, both are involved in the variable response to antiplatelet therapy.

Original languageEnglish
Pages (from-to)130-136
Number of pages7
JournalThrombosis Research
Volume123
Issue number1
DOIs
Publication statusPublished - 2008

Fingerprint

von Willebrand Factor
Blood Platelets
Interleukin-6
Acute Coronary Syndrome
Platelet Aggregation
Arachidonic Acid
Adenosine Diphosphate
Therapeutics
Percutaneous Coronary Intervention
Coronary Artery Disease
Collagen
Multivariate Analysis
Antigens

Keywords

  • ADAMTS-13
  • Antiaggregant therapy
  • Aspirin resistance
  • Residual platelet reactivity
  • von Willebrand Factor

ASJC Scopus subject areas

  • Hematology

Cite this

ADAMTS-13 activity in the presence of elevated von Willebrand factor levels as a novel mechanism of residual platelet reactivity in high risk coronary patients on antiplatelet treatment. / Marcucci, Rossella; Cesari, Francesca; Cinotti, Sandro; Paniccia, Rita; Gensini, Gian Franco; Abbate, Rosanna; Gori, Anna Maria.

In: Thrombosis Research, Vol. 123, No. 1, 2008, p. 130-136.

Research output: Contribution to journalArticle

Marcucci, Rossella ; Cesari, Francesca ; Cinotti, Sandro ; Paniccia, Rita ; Gensini, Gian Franco ; Abbate, Rosanna ; Gori, Anna Maria. / ADAMTS-13 activity in the presence of elevated von Willebrand factor levels as a novel mechanism of residual platelet reactivity in high risk coronary patients on antiplatelet treatment. In: Thrombosis Research. 2008 ; Vol. 123, No. 1. pp. 130-136.
@article{86c8e78384b84b65ba02598ea42b2e58,
title = "ADAMTS-13 activity in the presence of elevated von Willebrand factor levels as a novel mechanism of residual platelet reactivity in high risk coronary patients on antiplatelet treatment",
abstract = "Background: The pathophysiologic mechanisms leading to residual platelet reactivity (RPR) on antiplatelet therapy, a condition high prevalent in patients with acute coronary syndrome, are not yet elucidated. In the acute phase of coronary artery disease large amounts of ultra large VWF multimers (ULVWF) are released and cleaved by the activity of ADAMTS-13. Objective: Aim of this study was to evaluate the relationships between VWF antigen (VWF:Ag) levels, collagen binding activity of VWF (VWF:CB), ADAMTS-13 and interleukin-6 (IL-6) levels in affecting platelet response to dual antiplatelet treatment. Methods: In 159 acute coronary syndrome (ACS) patients undergoing percutaneous coronary interventions we measured platelet function by platelet aggregation with two agonists [1 mM arachidonic acid (AA) and 10 μM ADP]. We defined patients with RPR those with platelet aggregation by AA > 20{\%} and/or ADP (10 μmol) > 70{\%}. Results: We found significantly lower ADAMTS-13 activity, elevated IL-6, VWF:Ag and VWF:CB levels in patients with RPR. A lower ADAMTS-13 activity was present in patients with VWF:Ag and VWF:CB in the upper tertile. At the multivariate analysis ADAMTS-13 activity and IL-6 were independent risk factors for RPR. Conclusion: Our results indicate that ADAMTS-13 activity and IL-6 levels independently affect RPR and suggest that, by different pathways, both are involved in the variable response to antiplatelet therapy.",
keywords = "ADAMTS-13, Antiaggregant therapy, Aspirin resistance, Residual platelet reactivity, von Willebrand Factor",
author = "Rossella Marcucci and Francesca Cesari and Sandro Cinotti and Rita Paniccia and Gensini, {Gian Franco} and Rosanna Abbate and Gori, {Anna Maria}",
year = "2008",
doi = "10.1016/j.thromres.2008.05.017",
language = "English",
volume = "123",
pages = "130--136",
journal = "Thrombosis Research",
issn = "0049-3848",
publisher = "Elsevier Limited",
number = "1",

}

TY - JOUR

T1 - ADAMTS-13 activity in the presence of elevated von Willebrand factor levels as a novel mechanism of residual platelet reactivity in high risk coronary patients on antiplatelet treatment

AU - Marcucci, Rossella

AU - Cesari, Francesca

AU - Cinotti, Sandro

AU - Paniccia, Rita

AU - Gensini, Gian Franco

AU - Abbate, Rosanna

AU - Gori, Anna Maria

PY - 2008

Y1 - 2008

N2 - Background: The pathophysiologic mechanisms leading to residual platelet reactivity (RPR) on antiplatelet therapy, a condition high prevalent in patients with acute coronary syndrome, are not yet elucidated. In the acute phase of coronary artery disease large amounts of ultra large VWF multimers (ULVWF) are released and cleaved by the activity of ADAMTS-13. Objective: Aim of this study was to evaluate the relationships between VWF antigen (VWF:Ag) levels, collagen binding activity of VWF (VWF:CB), ADAMTS-13 and interleukin-6 (IL-6) levels in affecting platelet response to dual antiplatelet treatment. Methods: In 159 acute coronary syndrome (ACS) patients undergoing percutaneous coronary interventions we measured platelet function by platelet aggregation with two agonists [1 mM arachidonic acid (AA) and 10 μM ADP]. We defined patients with RPR those with platelet aggregation by AA > 20% and/or ADP (10 μmol) > 70%. Results: We found significantly lower ADAMTS-13 activity, elevated IL-6, VWF:Ag and VWF:CB levels in patients with RPR. A lower ADAMTS-13 activity was present in patients with VWF:Ag and VWF:CB in the upper tertile. At the multivariate analysis ADAMTS-13 activity and IL-6 were independent risk factors for RPR. Conclusion: Our results indicate that ADAMTS-13 activity and IL-6 levels independently affect RPR and suggest that, by different pathways, both are involved in the variable response to antiplatelet therapy.

AB - Background: The pathophysiologic mechanisms leading to residual platelet reactivity (RPR) on antiplatelet therapy, a condition high prevalent in patients with acute coronary syndrome, are not yet elucidated. In the acute phase of coronary artery disease large amounts of ultra large VWF multimers (ULVWF) are released and cleaved by the activity of ADAMTS-13. Objective: Aim of this study was to evaluate the relationships between VWF antigen (VWF:Ag) levels, collagen binding activity of VWF (VWF:CB), ADAMTS-13 and interleukin-6 (IL-6) levels in affecting platelet response to dual antiplatelet treatment. Methods: In 159 acute coronary syndrome (ACS) patients undergoing percutaneous coronary interventions we measured platelet function by platelet aggregation with two agonists [1 mM arachidonic acid (AA) and 10 μM ADP]. We defined patients with RPR those with platelet aggregation by AA > 20% and/or ADP (10 μmol) > 70%. Results: We found significantly lower ADAMTS-13 activity, elevated IL-6, VWF:Ag and VWF:CB levels in patients with RPR. A lower ADAMTS-13 activity was present in patients with VWF:Ag and VWF:CB in the upper tertile. At the multivariate analysis ADAMTS-13 activity and IL-6 were independent risk factors for RPR. Conclusion: Our results indicate that ADAMTS-13 activity and IL-6 levels independently affect RPR and suggest that, by different pathways, both are involved in the variable response to antiplatelet therapy.

KW - ADAMTS-13

KW - Antiaggregant therapy

KW - Aspirin resistance

KW - Residual platelet reactivity

KW - von Willebrand Factor

UR - http://www.scopus.com/inward/record.url?scp=54149097918&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=54149097918&partnerID=8YFLogxK

U2 - 10.1016/j.thromres.2008.05.017

DO - 10.1016/j.thromres.2008.05.017

M3 - Article

C2 - 18603284

AN - SCOPUS:54149097918

VL - 123

SP - 130

EP - 136

JO - Thrombosis Research

JF - Thrombosis Research

SN - 0049-3848

IS - 1

ER -