title: Preoperative platelet function predicts perioperative bleeding complications in ticagrelor-treated cardiac surgery patients: a prospective observational study.
abstract: BACKGROUND
  Treatment with P2Y12 receptor antagonists increases the risk for perioperative bleeding, but there is individual variation in the antiplatelet effect and time to offset of this effect. We investigated whether preoperative platelet function predicts the risk of bleeding complications in ticagrelor-treated cardiac surgery patients.
  
  
  METHODS
  Ninety patients with ticagrelor treatment within <5 days of surgery were included in a prospective observational study. Preoperative platelet aggregation was assessed with impedance aggregometry using adenosine diphosphate (ADP), arachidonic acid (AA), and thrombin receptor-activating peptide (TRAP) as initiators. Severe bleeding complications were registered using a new universal definition of perioperative bleeding. The accuracy of aggregability tests for predicting severe bleeding was assessed using receiver operating characteristic (ROC) curves, which also identified optimal cut-off values with respect to sensitivity and specificity, based on Youden's index.
  
  
  RESULTS
  The median time from the last ticagrelor dose to surgery was 35 (range 4-108) h. The accuracy of platelet function tests to predict severe bleeding was highest for ADP [area under the ROC curve 0.73 (95% confidence interval 0.63-0.84, P<0.001); TRAP 0.61 (0.49-0.74); AA 0.53 (0.40-0.66)]. The optimal cut-off for ADP-induced aggregation was 22 U. In subjects with ADP-induced aggregation below the cut-off value, 24/38 (61%) developed severe bleeding compared with 8/52 (14%) when aggregation was at or above the cut-off value (P<0.001). The positive and negative predictive values for this cut-off value were 63 and 85%, respectively.
  
  
  CONCLUSIONS
  Preoperative ADP-induced platelet aggregability predicts the risk for severe bleeding complications in ticagrelor-treated cardiac surgery patients.
authors.affiliation: Department of Cardiothoracic Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: C J
authors.initials: CJ
authors.lastname: Malm
authors.affiliation: Department of Cardiothoracic Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: E C
authors.initials: EC
authors.lastname: Hansson
authors.affiliation: AstraZeneca, Mölndal, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Åkesson
authors.affiliation: AstraZeneca, Mölndal, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Andersson
authors.affiliation: Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Hesse
authors.affiliation: Department of Cardiothoracic Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Shams Hakimi
authors.affiliation: Department of Cardiothoracic Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden anders.jeppsson@vgregion.se.
authors.forename: A
authors.initials: A
authors.lastname: Jeppsson
mesh_terms: D000241:Adenosine / Q000009:adverse effects / Q000031:analogs & derivatives*; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000368:Aged; D000369:Aged, 80 and over; D001792:Blood Platelets / Q000502:physiology*; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D017713:Platelet Transfusion; D019106:Postoperative Hemorrhage / Q000209:etiology*; D011446:Prospective Studies; D058921:Purinergic P2Y Receptor Antagonists / Q000009:adverse effects*; D000077486:Ticagrelor
chemical_list: D058921:Purinergic P2Y Receptor Antagonists; D000244:Adenosine Diphosphate; D000077486:Ticagrelor; D000241:Adenosine
keywords: acute coronary syndrome; blood platelets; cardiovascular surgery; haemorrhage; platelet function tests