Lower Platelet Aggregation Is a Risk Factor for Dual Antiplatelet Therapy-Associated Bleeding: A Preliminary Retrospective Study with Genotype Analysis

Med Sci Monit. 2020 Jun 16:26:e923758. doi: 10.12659/MSM.923758.

Abstract

BACKGROUND The purpose of this study was to investigate factors influencing bleeding in patients with acute coronary syndrome (ACS) who are on aspirin and ticagrelor as dual antiplatelet therapy. MATERIAL AND METHODS This retrospective case-control study included 50 patients with ACS (25 with reported bleeding events and 25 without) on aspirin and ticagrelor. Adenosine diphosphate (ADP)- and arachidonic acid (ACA)-induced platelet aggregation rates were measured using light transmission aggregometry. Single-nucleotide polymorphisms (SNPs) in PEAR1, GP1BA, and GSTP1 were genotyped. RESULTS ACA-induced platelet aggregation rates were obviously lower in patients with bleeding events than in those without (13.28±8.46% vs. 24.93±9.89%, P<0.001). No significant differences in ADP-induced platelet aggregation rates were observed between the 2 groups (16.17±9.74% vs. 16.88±12.69%, P>0.05). Among those with bleeding events and among controls, 70% and 80% had an ACA-induced platelet aggregation rate of 0-18% and 18-50%, respectively. Mutation rates of rs6065 in GP1BA and rs1695, rs4891, and rs8191439 in GSTP1 also differed significantly between the 2 groups. CONCLUSIONS Lower ACA-induced platelet aggregation rates are associated with increased risk of bleeding in patients with ACS who are on aspirin and ticagrelor. An ACA-induced platelet aggregation rate of 18% may be considered the cutoff point for identifying high risk of aspirin-associated bleeding events in patients with ACS. SNP genotyping may also help predict the risk of bleeding in patients with ACS.

MeSH terms

  • Acute Coronary Syndrome / therapy*
  • Adenosine Diphosphate
  • Aged
  • Arachidonic Acid
  • Aspirin / adverse effects*
  • Case-Control Studies
  • Dual Anti-Platelet Therapy / adverse effects
  • Female
  • Genotype
  • Glutathione S-Transferase pi / genetics
  • Hemorrhage / blood
  • Hemorrhage / chemically induced
  • Hemorrhage / genetics*
  • Humans
  • Male
  • Middle Aged
  • Percutaneous Coronary Intervention*
  • Platelet Aggregation Inhibitors / adverse effects*
  • Platelet Aggregation*
  • Platelet Glycoprotein GPIb-IX Complex / genetics
  • Polymorphism, Single Nucleotide
  • Receptors, Cell Surface / genetics
  • Retrospective Studies
  • Ticagrelor / adverse effects*

Substances

  • PEAR1 protein, human
  • Platelet Aggregation Inhibitors
  • Platelet Glycoprotein GPIb-IX Complex
  • Receptors, Cell Surface
  • adhesion receptor
  • Arachidonic Acid
  • Adenosine Diphosphate
  • GSTP1 protein, human
  • Glutathione S-Transferase pi
  • Ticagrelor
  • Aspirin