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.
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 microM ADP]. We defined patients with RPR those with platelet aggregation by AA >20% and/or ADP (10 micromol) >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.


CONCLUSIONS
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.
Marcucci
Rossella
R
Department of Medical and Surgical Critical Care, Thrombosis Centre, University of Florence, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy. rossella.marcucci@unifi.it
Cesari
Francesca
F
Cinotti
Sandro
S
Paniccia
Rita
R
Gensini
Gian Franco
GF
Abbate
Rosanna
R
Gori
Anna Maria
AM
D051722:ADAM Proteins / Q000378:metabolism*; D000071120:ADAMTS13 Protein; D054058:Acute Coronary Syndrome / Q000097:blood / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015906:Angioplasty, Balloon, Coronary; D001792:Blood Platelets / Q000187:drug effects*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D014841:von Willebrand Factor / Q000032:analysis*
D015850:Interleukin-6; D010975:Platelet Aggregation Inhibitors; D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human