Platelet-Mediated Thrombosis: From Bench to Bedside

Circ Res. 2016 Apr 29;118(9):1380-91. doi: 10.1161/CIRCRESAHA.115.307016.

Abstract

The pivotal role that platelets play in thrombosis and resultant ischemic event occurrences in patients with high-risk coronary artery disease is well established. This role provides the fundamental basis for the current wide implementation of dual antiplatelet therapy with aspirin and a P2Y12 receptor inhibitor. The development of user friendly point-of-care methods to assess platelet reactivity to adenosine diphosphate has increased the frequency of platelet function testing in clinical practice. Recent large observational studies have established an independent relation between the results of point-of-care platelet function testing and clinical event occurrence in patients undergoing coronary artery stenting. However, prospective, randomized trials have failed to demonstrate that personalized antiplatelet therapy based on point-of-care assessment of platelet function is effective in reducing ischemic event occurrences. Important limitations were associated with these trials. In addition, the concept of a therapeutic window of P2Y12 receptor reactivity with an upper threshold associated with ischemic event occurrence and a lower threshold associated with bleeding has also been proposed. In the absence of strong prospective evidence to support personalized antiplatelet therapy, clinical decision making about antiplatelet therapy rests on the large body of observational data and the fundamental importance of platelet physiology in catastrophic event occurrence in patients with high-risk coronary artery disease.

Keywords: antiplatelets; bleeding; platelet function inhibitors; platelet function testing; platelets; thrombosis.

Publication types

  • Review

MeSH terms

  • Animals
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Blood Platelets / pathology
  • Clinical Trials as Topic
  • Coronary Thrombosis / drug therapy*
  • Coronary Thrombosis / metabolism
  • Coronary Thrombosis / pathology
  • Humans
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / pharmacology
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Precision Medicine / methods
  • Receptors, Purinergic P2Y12 / metabolism
  • Translational Research, Biomedical / methods*

Substances

  • Platelet Aggregation Inhibitors
  • Receptors, Purinergic P2Y12