Open AccessPlatelet CD 40 ligand and bleeding during P2Y12 inhibitor treatment in acute coronary syndrome
Author(s) -
Grosdidier Charlotte,
Blanz Kelly D.,
Deharo Pierre,
Bernot Denis,
Poggi Marjorie,
Bastelica Delphine,
Wolf Dennis,
Duerschmied Daniel,
Grino Michel,
Cuisset Thomas,
Alessi MarieChristine,
Canault Matthias
Publication year - 2019
Publication title -
research and practice in thrombosis and haemostasis
Language(s) - English
Resource type - Journals
ISSN - 2475-0379
DOI - 10.1002/rth2.12244
Subject(s) - p2y12 , platelet , medicine , ticagrelor , acute coronary syndrome , thrombus , platelet activation , clopidogrel , cd40 , odds ratio , cardiology , adenosine diphosphate , myocardial infarction , platelet aggregation , chemistry , in vitro , biochemistry , cytotoxic t cell
Abstract Antiplatelet therapy through inhibition of the adenosine diphosphate ( ADP )/P2Y12 pathway is commonly used in the treatment of acute coronary syndrome ( ACS ). Although efficient in preventing platelet activation and thrombus formation, it increases the risk of bleeding complications. In patients with ACS receiving platelet aggregation inhibitors, that is, P2Y12 blockers (n = 923), we investigated the relationship between plasma and platelet‐associated CD 40L levels and bleeding events (n = 71). Treatment with P2Y12 inhibitors in patients with ACS did not affect plasma‐soluble CD 40L levels, but decreased platelet CD 40L surface expression ( pCD 40L) and platelet‐released CD 40L ( rCD 40L) levels in response to stimulation as compared to healthy controls. In vitro inhibition of the ADP pathway in healthy control platelets reduced both pCD 40L and rCD 40L levels. In a multivariable analysis, the reduced pCD 40L level observed in ACS patients was significantly associated with the risk of bleeding occurrence (adjusted odds ratio = 0.15; 95% confidence interval = 0.034‐0.67). P2Y12 inhibitor‐treated (ticagrelor) mice exhibited a 2.5‐fold increase in tail bleeding duration compared with controls. A significant reduction in bleeding duration was observed on CD 40L +/+ but not CD 40L −/− platelet infusion. In addition, CD 40L blockade in P2Y12 inhibitor–treated blood samples from a healthy human reduced thrombus growth over immobilized collagen under arterial flow. In conclusion, measurement of pCD 40L may offer a novel approach to assessing bleeding risk in patients with ACS who are being treated with P2Y12 inhibitors.